POPULARITY
5 episodes with psma pet
3 episodes with psma pet
3 episodes with psma pet
3 episodes with psma pet
3 episodes with psma pet
2 episodes with psma pet
2 episodes with psma pet
3 episodes with psma pet
4 episodes with psma pet
AUA2025: Embracing Multi-Disciplinary Care for Advanced Prostate Cancer: A Case-Based Update 2025 CME Available: https://auau.auanet.org/node/42997 At the conclusion of this activity, participants will be able to: 1. Initial Management of Metastatic Prostate Cancer: Evaluate and treat a patient with new diagnosed M1 prostate cancer with androgen deprivation therapy (ADT) plus be skilled to offer novel oral antiandrogens. Furthermore, to recognize high-volume new M1 prostate cancer so as to be able to partner with GU medical oncologist for docetaxel chemotherapy in a multidisciplinary team. 2. Non-Metastatic Castrate Resistant Prostate Cancer (M0 CRPC): The learner will be skilled to diagnose M0 CRPC and be able to educate patients about using either enzalutamide or apalutamide or darolutamide added to traditional ADT as a way to improve their patent's overall and radiographic progression-free survival. Furthermore, the skilled learner will be able to understand the differences between these three oral agents and to educate patients about side-effects and toxicities. Finally, understand the pros and cons of PSMA PET scan imaging in further staging in this disease Non-metastatic Castrate-Resistant Prostate Cancer (M0 CRPC): Diagnose M0 CRPC and be able to educate patients about using novel oral antiandrogens added to traditional ADT as a way to improve their patent's overall and radiographic progression-free survival. Furthermore, the skilled learner will be able to understand the differences between these novel oral agents and to educate patients about side effects and toxicities. Finally, understand the pros and cons of PSMA PET scan imaging in further staging in this disease state. 3. Metastatic Castrate-Resistant Prostate Cancer (M1 CRPC): Describe and have a working knowledge of the latest phase III RCT results for new therapies in M1 CRPC and be able to educate their patients on treatment options and participate in a multidisciplinary team caring for men with this disease state of far-advanced prostate cancer. 4. Describe that advanced prostate cancer is a complex group of disease states with an ever-changing therapeutic landscape and for providers and teams to embrace the multi-disciplinary nature of care for our patients. 5. Identify the molecular and molecular genetic underpinnings of advanced prostate cancer and recognize the future will be based on a more personalized therapy landscape including PARP inhibition, immune checkpoint agents, and novel AR targeted agents emerging in 2025 and beyond.
AUA2025: Integration of Biomarkers, MRI and PSMA PET Imaging Into the Management of Prostate Cancer CME Available: https://auau.auanet.org/node/43069 At the conclusion of this CME activity, participants will be able to: 1. Evaluate recent advances in biomarkers and molecular imaging technologies and their role in improving the accuracy of prostate cancer staging, and treatment monitoring. 2. Identify the clinical scenario in which PSMA PET/CT is most helpful to identify the localization and extent of locoregional or systemic metastatic disease. 3. Identify the pitfalls of false-positive and false-negative PSMA PET/CT findings. 4. Apply the findings of PSMA PET/CT for the best individual therapeutic approach. 5. Identify patients with radiorecurrent organ-confined prostate cancer. ACKNOWLEDGEMENTS Support provided by independent educational grants from: Blue Earth Diagnostics, Inc. Lantheus Medical Imaging Novartis Pharmaceuticals Corporation
Dr. Rohan Garje shares the updated recommendations for the ASCO guideline on systemic therapy for patients with metastatic castration-resistant prostate cancer. He discusses the systemic therapy options for patients based on prior therapy received in the castration-sensitive and non-metastatic castration-resistant settings. He emphasizes personalizing treatment choices for each individual, considering patient-specific symptoms and signs, treatment-related toxicities, potential drug interactions, cost, and access. He also reviews recommendations on response assessment. The conversation wraps up with a discussion of potential future updates to this guideline, as the guideline transitions into a “living guideline” on mCRPC. Read the full guideline update, “Systemic Therapy in Patients with Metastatic Castration-Resistant Prostate Cancer: ASCO Guideline Update”. Transcript This guideline, clinical tools, and resources are available at www.asco.org/genitourinary-cancer-guidelines. Read the full text of the guideline and review authors' disclosures of potential conflicts of interest in the Journal of Clinical Oncology. Brittany Harvey: Hello and welcome to the ASCO Guidelines Podcast, one of ASCO's podcasts delivering timely information to keep you up to date on the latest changes, challenges and advances in oncology. You can find all the shows, including this one at asco.org/podcasts. My name is Brittany Harvey and today I'm interviewing Dr. Rohan Garje from Miami Cancer Institute Baptist Health South Florida, lead author on, “Systemic Therapy in Patients with Metastatic Castration-Resistant Prostate Cancer: ASCO Guideline Update.” Thank you for being here today, Dr. Garje. Dr. Rohan Garje: Absolutely. Thank you so much for having me, Brittany. Brittany Harvey: And then before we discuss this guideline, I'd like to note that ASCO takes great care in the development of its guidelines and ensuring that the ASCO Conflict of Interest Policy is followed for each guideline. The disclosures of potential conflicts of interest for the guideline panel, including Dr. Garje, who has joined us here today, are available online with the publication of the guideline in the Journal of Clinical Oncology, which is linked in the show notes. So then, to start on the content of this guideline, first, could you provide us an overview of the purpose of this guideline update? Dr. Rohan Garje: Sure. So ASCO has guidelines for prostate cancer and the specific guideline which we have updated for metastatic castrate-resistant prostate cancer was originally published in 2014. It's almost a decade. It's been a long time due for an update. Over the last decade, we have seen a lot of advances in the treatment of prostate cancer, specifically with regards to genomic testing, newer imaging modalities, and also the treatment landscape. Now we have newer options based on genomic targets such as PARP inhibitors, we have radiopharmaceuticals, a newer variant of chemotherapy, and also some specific indications for immunotherapy which were not addressed previously. Because all these advances have been new, it was really important for us to make an update. In 2022, we did make a rapid update with lutetium-177, but these additional changes which we have seen made it an appropriate time frame for us to proceed with a newer guideline. Brittany Harvey: Absolutely. It's great to hear about all these advances in the field to provide new options. So I'd like to next review the key recommendations from this guideline. So let's start with the overarching principles of practice that the panel outlined. What are these key principles? Dr. Rohan Garje: As a group, all the panel members came up with some ground rules: What are necessary for all our patients who are being treated for metastatic CRPC? First, the founding aspect was a definition for what is metastatic CRPC. So we defined metastatic CRPC as castrate level of testosterone with evidence of either new or progressive metastatic disease on radiological assessments or patients who have two consecutive rising PSAs in the setting of existing metastatic disease. We also emphasized on the need for germline and somatic testing for patients with metastatic prostate cancer at an earliest available opportunity because it is critical to select appropriate treatment and also right treatment for patients at the right time. And we actually have a concurrent guideline which addresses what genes to be tested and the timing. The other principles are patients should continue to receive androgen deprivation therapy or undergo surgical castration to maintain castrate level of testosterone. Now the key aspect with these guidelines is personalizing treatment choices. As you can see the evolution of treatment options for prostate cancer, the drugs that were initially developed and approved for prostate cancer were primarily in castrate-resistant settings, but now most of these drugs are being utilized in castrate-sensitive. So, when these patients develop castration resistance, the challenges are there are no appropriate particular drug-specific guidelines they meet. So, it's very important for the clinicians to be aware of what treatments have been received so far prior to castration resistance so that they can tailor the treatment to patient specific situations. In addition, prior to choosing a therapy, it is important for the physicians to consider patient specific symptoms or signs, treatment-related toxicities, potential drug interactions, cost, and also access to the drugs. There may be multiple treatment options available for the patients, but for a patient specific scenario, there may be a drug that may be more promising than the others. So, it is important to tailor the drug choices based on patients' unique circumstances. The panel also recommends to early integrate palliative and supportive care teams for symptom management and also discuss goals of care with the patient as each patient may have unique needs and it's important for physicians to address those concerns upfront in the care. The panel also suggests patients to receive RANK ligand inhibitors such as denosumab or bisphosphonates such as zoledronic acid to maintain the bone strength to prevent skeletal-related events. Finally, I would like to also emphasize this point about the lack of randomized clinical trial data for optimal sequencing of therapies for patients with metastatic CRPC. As I previously alluded, we have taken into account all ongoing clinical trials, prior published data, and came up with a format of preferred drugs based on prior treatments and, I think, by following these several clinical principles which I just mentioned, we can optimally choose and utilize best treatments for patients with metastatic CRPC. Brittany Harvey: Absolutely. These principles that you just outlined are important for optimal patient care, and then I want to touch on one of those things. You talked importantly about the treatments received so far. So in the next set of recommendations, the role of systemic therapy was stratified by the prior therapy received in the castration-sensitive and non-metastatic castration-resistant setting. So starting with what does the panel recommend for patients who are previously treated with androgen deprivation therapy alone in these previous settings and whose disease has now progressed to metastatic castration-resistant prostate cancer? Dr. Rohan Garje: There are multiple treatment options based on prior treatment received. So for patients who received only ADT for their castration-sensitive disease, the panel strongly urges to get HRR testing to check for homologous recombinant repair related changes, specifically for BRCA1 and BRCA2 mutations, because we have three studies which have really shown significant clinical benefit for patients who have BRCA1 and BRCA2 mutations with drugs such as the combination of talazoparib and enzalutamide or olaparib with abiraterone or niraparib with abiraterone. Unless we test for those mutations, we'll not be able to give these agents upfront for the patients. In the HRR testing, if patients have HRR alterations but they are in genes which are non-BRCA, the guideline panel recommends to utilize talazoparib and enzalutamide based combination therapies. Now, if they don't have HRR alterations then there are multiple treatment choices available. It could either include androgen receptor pathway inhibitors such as abiraterone with prednisone. We could also consider docetaxel chemotherapy. The alternate choices for androgen receptor pathways include enzalutamide or the newer agents such as apalutamide and docetaxel. So, as you can see there are multiple options available, but the panel definitely emphasizes to test for HRR testing because this gives patients access to more precision therapies at this point. There may be various scenarios where a unique drug may be available for a specific patient situation. For example, patients who have very limited disease burden and may have one or two metastatic lesions, after a multidisciplinary discussion, targeted local therapies such as radiation or potentially surgery could also be offered. In select patients who have very indolent disease where they are castrate-resistant based on slow rising PSA, low-volume disease or asymptomatic disease can consider sipuleucel-T. And in patients who have bone-only metastatic disease, we could also consider radium-223, which is primarily now utilized for patients who have symptomatic bone disease. Brittany Harvey: Great. I appreciate you reviewing all those options and talking about how important it is to tailor treatment to the individual patient. So then the next category of patients, what is recommended for those who have been previously treated with ADT and an androgen receptor pathway inhibitor and whose disease has now progressed to metastatic castration-resistant prostate cancer? Dr. Rohan Garje: So for patients who received ADT along with an androgen receptor pathway inhibitor, which we consider would be a most common cohort because most patients now in castration-sensitive setting are receiving androgen receptor pathway inhibitor. It was different in the past where five or six years back ADT alone was the most common treatment, but fortunately, with enough awareness and education, treatment choices have improved. Patients are now receiving ADT and ARPI as the most common choice of drug. Once again, at this point the panel emphasizes to consider HRR testing in there is enough data for us to suggest that patients who have alterations in the HRR pathway definitely will benefit with the PARP inhibitor. You know the multiple options, but specifically we speak about olaparib. And then if they are HRR-negative, we prefer patients receive agents such as docetaxel or if they are intolerant to docetaxel, consider cabazitaxel chemotherapy, options such as radium-223, and if they have a specific scenario such as MSI-high or mismatch repair deficiency, pembrolizumab could also be considered. The panel also discussed about the role of a second ARPI agent. For example, if patients progressed on one androgen receptor pathway inhibitor, the second androgen receptor pathway inhibitor may not be effective and the panel suggests to utilize alternate options before considering androgen receptor pathway inhibitor. There may be specific scenarios where a second ARPI may be meaningful, specifically, if alternate choices are not feasible for the concern of side effects or toxicities or lack of access, then a potential ARPI could be considered after progression on ARPI, but the panel definitely encourages to utilize alternate options first. Brittany Harvey: Great. Thank you for outlining those options as well for those patients. So then the next category, what is recommended for patients who have been previously treated with ADT and docetaxel? Dr. Rohan Garje: For patients who received ADT and docetaxel and were never treated with androgen receptor pathway inhibitors, the panel again emphasizes on HRR testing. If they have BRCA1 and 2 mutations, the combination therapies of talazoparib with enzalutamide, olaparib with abiraterone, or niraparib with abiraterone are all good choices. If they don't have BRCA mutations but they have other HRR mutations, the panel suggests to potentially utilize talazoparib with enzalutamide. And if they do not have any HRR alterations, the options could include androgen receptor pathway inhibitors such as abiraterone or enzalutamide. I want to emphasize that these are preferred options, but not the only options. As you can see, there are multiple options available for a particular clinical situation - so the ability of the physicians to access particular combinations, the familiarity of those drugs or the patient's unique situation where they have other medications which can potentially interact with a choice of agents. So I think based on access, based on cost and patients' concurrent illness with potential drug interactions can make one particular combination of therapy better over the other options. Brittany Harvey: Absolutely. That's key to keep in mind that access, contraindications, and cost all play a role here. So then the next set of recommendations. What are the key recommendations for patients who have previously been treated with ADT, an androgen receptor pathway inhibitor, and docetaxel who now have mCRPC? Dr. Rohan Garje: Yes. In this group, the options remain, again, broad. We utilize PSMA imaging here specifically and if they are positive on PSMA imaging, lutetium-177 is a good option. If they do not have PSMA-positive disease on PSMA imaging but if they have HRR alterations, olaparib could be utilized. And if they are negative on PSA imaging, they don't have HRR alterations, then alternate options could include cabazitaxel, radium-223. And if they have MSI-high or deficiency in mismatch repair, pembrolizumab could be utilized in this setting. Brittany Harvey: Thank you for outlining those options as well. So then next the panel addressed treatment options for de novo or treatment emergent small cell neuroendocrine carcinoma of the prostate. What are those key recommendations? Dr. Rohan Garje: Yes. This is a very high unmet need group because there are limited clinical trials, especially prospective clinical trials addressing treatment options for this group. Most of our current guidelines are always an extrapolation from lung small cell cancer based guidelines, but the panel recommends to utilize cisplatin or carboplatin along with etoposide as a preferred choice for this group. Also, an alternate option of carboplatin along with cabazitaxel could be considered for this cohort. The panel also encourages participation in clinical trials. There are numerous trials ongoing now in smaller phase studies and I think it's important for patients to consider these trials as well, because this will give them access to newer agents with potential biological targets. In addition to these agents in specific scenarios or potentially case by case basis, because we don't have prospective data, so we have made it as a select case by case basis to consider adding immunotherapy along with platinum-based chemotherapy followed by maintenance immunotherapy, which is currently a standard of care in small cell lung cancer. But the data is so limited in prostate cancer, so the panel suggested that it has to be a case by case basis only. The alternate options also include lurbinectedin, topotecan, tarlatamab upon progression on platinum-based chemotherapy. Brittany Harvey: Yes. It's important to have these recommendations in these unique situations where there is really a lack of data. So then the final set of recommendations I'd like to cover, what does the panel recommend for how clinicians should assess for response while patients are on systemic therapy and what scans are recommended for this response assessment? Dr. Rohan Garje: Yes. Again, this is another strong emphasis of the panel for global assessment of the patients. Traditionally, patients and physicians per se are heavily reliant on PSA as an accurate marker for response. This is in fact true in earlier phases of prostate cancer either in castrate-sensitive setting or localized prostate cancer setting. But as patients evolve into castrate-resistant, we don't want to heavily rely on PSA alone as a marker of response. The panel suggests to incorporate clinical response, radiological response, and also include PSA as a component, but not just rely primarily on PSA. So the panel also suggests that patients should get a bone scan and a CT scan every three to six months while on treatment to assess for appropriate response or for progression. And now one key important aspect, we are all aware about the evolving role of PSMA-based imaging with several of these new agents that are currently available. We do acknowledge these scans definitely have an important role in the care for patients with metastatic prostate cancer. Currently, the utility is primarily to select patients for lutetium-based therapy and also in situations where the traditional scans such as technitium 99 bone scan or CT scan are equivocal, then a PSMA-based imaging can be helpful. Now we are also aware that there are newer studies coming up, prospective data coming up for the role of PSMA-based imaging for response assessment. We are hoping to update the guidelines if we get access to newer data, but currently we have not recommended the utility of PSMA-based imaging for response assessments. Brittany Harvey: Understood. And I appreciate you describing where there is data here and where there's a lack of data to currently recommend. And we'll look forward to future updates of this guideline. Coming back to – at the start you mentioned how much has changed since the last guideline update. So Dr. Garje, in your view, what is the importance of this update and how will it impact both clinicians and patients with metastatic castration-resistant prostate cancer? Dr. Rohan Garje: The updated guidelines are designed to have a significant impact on clinical practice and also patient outcomes by providing clinicians with a comprehensive evidence-based framework for managing patients with metastatic CRPC. And also, by using these guidelines can make informed decisions, can select therapies tailored to patients' unique genomic status, clinical situation, where they are in the course of the cancer based on what they received previously. Also utilizing these guidelines, we can potentially improve patient outcomes, improve survival, and importantly have efficient use of healthcare resources. Brittany Harvey: Absolutely. We're always looking for ways to improve patient outcomes and survival. I want to wrap us up by talking a little bit about the outstanding questions in this field. So earlier you had mentioned about prospective data to come about PSMA PET scans, but what other outstanding questions are there for patients with metastatic castration-resistant prostate cancer? And what evidence is the panel looking forward to for future updates? Dr. Rohan Garje: We do have now rapidly evolving data specifically about the utility of the radiopharmaceutical lutetium-177 prior to chemotherapy. We are hoping that with newer data we can make some changes to the guideline based on that. We are also looking at newer drugs that are coming up in the pipeline, for example, androgen receptor degraders. We are looking at data that might potentially help based on bispecific T-cell engagers and newer radiopharmaceuticals. So I think in the next few years, we will definitely update all the guidelines again. But this time we are trying to do it more proactively. We are following a newer model. We are calling it as ‘living guidelines' where we are actually utilizing week by week updates where we look at the literature and see if there is any potential practice impacting change or publication that comes up. And we are trying to incorporate those changes as soon as they are available. That way patients and practicing physicians can get the latest information available through the guidelines as well. Brittany Harvey: That's great to hear. Yes, we'll await this data that you mentioned to continuously update this guideline and continue to improve patient outcomes for the future. So Dr. Garje, I want to thank you so much for your time to update this guideline. It was certainly a large amount of recommendations, and thank you for your time today, too. Dr. Rohan Garje: Thank you so much for having me here. And it's always nice talking to you. Brittany Harvey: And finally, thank you to our listeners for tuning in to the ASCO Guidelines podcast. To read the full guideline, go to www.asco.org/genitourinary-cancer-guidelines. You can also find many of our guidelines and interactive resources in the free ASCO Guidelines app, which is available in the Apple App Store or the Google Play Store. If you have enjoyed what you've heard today, please rate and review the podcast and be sure to subscribe so you never miss an episode. The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.
In this informative episode, Dr. Aly-Khan Lalani and Dr. Christopher Wallis are joined by Dr. Frédéric Pouilot, a urologist-oncologist and researcher in molecular imaging at the CHU de Québec-Université Laval Research Center. Together, they unpack the evolving role of PSMA PET in prostate cancer and how advanced imaging tools are reshaping treatment decisions. The conversation also looks ahead, to the future of dynamic imaging, and its potential to revolutionize personalized cancer care.The View on GU with Lalani & Wallis integrates key clinical data from major conferences and high impact publications, sharing meaningful take home messages for practising clinicians in the field of genitourinary (GU) cancers. Learn more about The View on GU: theviewongu.caThis podcast has been made possible through unrestricted financial support by Novartis, Bayer, Astellas, Tolmar, J&J, Merck, Pfizer, Eisai and AbbVie.
In this episode of the Dr. Geo Prostate Podcast, we welcome Dr. Jonathan Lischalk, Director of Genitourinary Cancers at MedStar Georgetown University Hospital and former Medical Director at NYU's NYCyberKnife Center. Dr. Lischalk breaks down the evolution of radiation oncology and how cutting-edge imaging and targeted SBRT (Stereotactic Body Radiation Therapy) are reshaping prostate cancer treatment.We explore how imaging advances like MRI and PSMA PET scans are enabling unprecedented precision, the future of genetic-based personalization in prostate cancer therapy, and why fewer, more focused radiation sessions might soon become the new standard. From understanding the biology of radiation dosing to upcoming trials eliminating ADT in select patients, this is a must-listen for anyone looking to stay informed on the forefront of cancer care.
In this episode of the Dr. Geo Prostate Podcast, Dr. Geo welcomes Dr. Alberto Vargas, Vice Chair of Oncologic Imaging at NYU Langone Health and expert in prostate cancer imaging.They dive deep into the evolving world of diagnostic tools—MRI, PET, CT, and PSMA scans—and how these technologies help detect, monitor, and guide treatment for prostate cancer. Dr. Vargas explains the difference between imaging modalities, when to use them, and how PSMA PET scans are changing the game in identifying recurrent and metastatic disease earlier than ever before.Key topics covered:MRI vs. PET vs. CT: what each scan shows and when it matters mostThe rise of PSMA PET for finding prostate cancer at extremely low PSA levelsWhy not all PET scans are the same, and how tracers like FDG, Axumin, and PSMA workThe potential future of prostate cancer diagnosis: fewer biopsies, more imagingLimitations, false positives, and how imaging results are interpretedThe role of imaging in both first-time diagnosis and recurrenceWhether you're a patient, caregiver, or clinician, this episode offers valuable insight into how imaging helps guide smart, proactive decisions in prostate cancer care.----------------Thank you to our partnersThe ProLon 5-Day Fasting Mimicking Diet is a plant-based meal program designed to provide fasting benefits while allowing food intake. Developed by Dr. Valter Longo, it supports cellular renewal, fat loss, and metabolic health through low-calorie, pre-packaged meals that maintain the body in a fasting state.Special Offer: Thank you for listening, you can purchase the ProLon kit for just $148 by using this link.We'd also like to thank our partner AG1 by Athletic Greens. AG1 contains 75 high-quality vitamins, minerals, whole-food sourced ingredients, probiotics, and adaptogens to help you start your day right. This special blend of ingredients supports your gut health, nervous system, immune system, energy, recovery, focus, and aging. All the essentials in one scoop. Enjoy AG1 by Athletic Greens.----------------Thanks for listening to this week's episode. Subscribe to The Dr. Geo YouTube Channel to get more content like this and learn how you can live better with age.You can also listen to this episode and future episodes of the Dr. Geo Podcast by clicking HERE.----------------Follow Dr. Geo on social media. Facebook, Instagram Click here to become a member of Dr. Geo's Health Community.Improve your urological health with Dr. Geo's formulated supplement lines:XY Wellness for Prostate cancer lifestyle and nutrition: Mr. Happy Nutraceutical Supplements for prostate health and male optimal living.You can also check out Dr. Geo's online dispensary for other supplement recommendations Dr. Geo's Supplement...
In this episode of the Dr. Geo Prostate Podcast, Dr. Geo welcomes Dr. Alberto Vargas, Vice Chair of Oncologic Imaging at NYU Langone Health and expert in prostate cancer imaging.They dive deep into the evolving world of diagnostic tools—MRI, PET, CT, and PSMA scans—and how these technologies help detect, monitor, and guide treatment for prostate cancer. Dr. Vargas explains the difference between imaging modalities, when to use them, and how PSMA PET scans are changing the game in identifying recurrent and metastatic disease earlier than ever before.Key topics covered:MRI vs. PET vs. CT: what each scan shows and when it matters mostThe rise of PSMA PET for finding prostate cancer at extremely low PSA levelsWhy not all PET scans are the same, and how tracers like FDG, Axumin, and PSMA workThe potential future of prostate cancer diagnosis: fewer biopsies, more imagingLimitations, false positives, and how imaging results are interpretedThe role of imaging in both first-time diagnosis and recurrenceWhether you're a patient, caregiver, or clinician, this episode offers valuable insight into how imaging helps guide smart, proactive decisions in prostate cancer care.----------------Thank you to our partnersThe ProLon 5-Day Fasting Mimicking Diet is a plant-based meal program designed to provide fasting benefits while allowing food intake. Developed by Dr. Valter Longo, it supports cellular renewal, fat loss, and metabolic health through low-calorie, pre-packaged meals that maintain the body in a fasting state.Special Offer: Thank you for listening, you can purchase the ProLon kit for just $148 by using this link.We'd also like to thank our partner AG1 by Athletic Greens. AG1 contains 75 high-quality vitamins, minerals, whole-food sourced ingredients, probiotics, and adaptogens to help you start your day right. This special blend of ingredients supports your gut health, nervous system, immune system, energy, recovery, focus, and aging. All the essentials in one scoop. Enjoy AG1 by Athletic Greens.----------------Thanks for listening to this week's episode. Subscribe to The Dr. Geo YouTube Channel to get more content like this and learn how you can live better with age.You can also listen to this episode and future episodes of the Dr. Geo Podcast by clicking HERE.----------------Follow Dr. Geo on social media. Facebook, Instagram Click here to become a member of Dr. Geo's Health Community.Improve your urological health with Dr. Geo's formulated supplement lines:XY Wellness for Prostate cancer lifestyle and nutrition: Mr. Happy Nutraceutical Supplements for prostate health and male optimal living.You can also check out Dr. Geo's online dispensary for other supplement recommendations
Check out this week's QuadCast where we highlight the link between dental hygiene and oral mucositis risk, the optimal timing of post-treatment PSMA PET scans, the impressive impact of immunotherapy in MSI-high colorectal cancer, and more. Check out the website and subscribe to the newsletter! www.quadshotnews.com Founders & Lead Authors: Laura Dover & Caleb Dulaney Podcast Host: Sam Marcrom
Declan Murphy is in the GU Cast studio in Shanghai with GU Cast China Editor, Prof Yao Zhu. We sit down with Prof Hao Zeng (West China Hospital) and Dr Ye Yan to discuss their experiences and perspectives on advancements in diagnostics like MRI and PSMA PET, the increasing use of Chinese-developed robotic surgery platforms, and the ongoing debate surrounding pelvic lymph node dissection. They also address the application of systemic therapies for metastatic disease, considering the unique characteristics of the Chinese patient population and the potential for dose adjustments. Today's pod also highlights the growing importance of precision oncology, including genomic testing for mutations to guide treatment decisions, while acknowledging the challenges and future directions in this area.This is a Themed Podcast supported by our Gold Partner, Bayer China. Even better on our YouTube channel https://youtu.be/xlOuS4swcuc
Prostate specific membrane antigen or PSMA PET scanning is very accurate at detecting and visualizing prostate cancer throughout the body. Now a study using this type of scan on men whose disease recurred shows its efficacy in this case also. … When prostate cancer returns a nuclear medicine scan can help, Elizabeth Tracey reports Read More »
Send us a textWelcome to the 21st edition of DigiPath Digest! In this episode, together with Dr. Aleksandra Zuraw you will review the latest digital pathology abstracts and gain insights into emerging trends in the field. Discover the promising results of the PSMA PET study for prostate cancer imaging, explore the collaborative open-source platform HistioColAI for enhancing histology image annotation, and learn about AI's role in improving breast cancer detection. Dive into topics such as the role of AI in renal histology classification, the innovative TrueCam framework for trustworthy AI in pathology, and the latest advancements in digital tools like QuPath for nephropathology. Stay tuned to elevate your digital pathology game with cutting-edge research and practical applications.00:00 Introduction to DigiPath Digest #2101:22 PSMA PET in Prostate Cancer06:49 HistoColAI: Collaborative Digital Histology12:34 AI in Mammogram Analysis17:21 Blood-Brain Barrier Organoids for Drug Testing22:02 Trustworthy AI in Lung Cancer Diagnosis30:09 QuPath for Nephropathology35:30 AI Predicts Endocrine Response in Breast Cancer40:04 Comprehensive Classification of Renal Histologic Types45:02 Conclusion and Viewer EngagementLinks and Resources:Subscribe to Digital Pathology Podcast on YouTubeFree E-book "Pathology 101"YouTube (unedited) version of this episodeTry Perplexity with my referral linkMy new page built with PerplexityHistoColAI Github PagePublications Discussed Today:
What is the role of androgen deprivation therapy (ADT) in prostate cancer treatment? In this episode of the BackTable Urology Podcast, Dr. Rana McKay, a medical oncologist from UC San Diego, joins host Dr. Aditya Bagrodia to discuss the administration of ADT and other management strategies for prostate cancer. --- This podcast is supported by: Photocure https://www.photocure.com/ --- SYNPOSIS The doctors offer a historical perspective into the evolution of ADT over time and discuss the variety of different ADT treatment options available. They compare management strategies for localized and metastatic prostate cancer and discuss how to align therapy with patient goals, focusing on the side effects. The conversation also explores the impact of prostate-specific membrane antigen (PSMA) PET imaging on management and the future directions of hormonal therapies in urologic oncology. --- TIMESTAMPS 00:00 - Introduction 05:25 - ADT Options 10:36 - Choosing an Agent and Managing Side Effects 26:42 - Continuous Versus Intermittent Therapy 30:30 - Closing Remarks --- RESOURCES Photocure https://www.photocure.com/
In this two-part episode of the Precision Medicine Podcast, host Karan Cushman continues her deep dive into prostate cancer care with expert guest Dr. William Oh, a leading genitourinary oncologist, Director of Precision Medicine at Yale Cancer Center and Chair of the American Cancer Society National Prostate Cancer Roundtable. Building on part one (episode 63), they explore the transformative role of precision medicine, advanced diagnostics, and targeted therapies—emphasizing the urgent need for greater awareness, understanding, and advocacy as prostate cancer continues to rise steadily. Karan opens the conversation by emphasizing the growing complexity of prostate cancer diagnostics and treatment. Dr. Oh discusses the wide array of diagnostic tools, from PSA tests and MRIs to the cutting-edge PSMA PET scan, which has revolutionized staging and treatment planning by providing detailed insights into cancer spread. He highlights how these tools are helping oncologists tailor treatment plans with unprecedented precision. The discussion shifts to molecular diagnostics, a burgeoning field that provides critical information about the aggressiveness of cancer. Dr. Oh explains how molecular tests, such as genomic profiling, are enabling personalized treatment decisions for prostate cancer patients, particularly those on the fence about options like surgery, radiation, or active surveillance. Karan and Dr. Oh also address disparities in access to these advanced diagnostics, underlining the need for wider implementation. Karan steers the conversation toward advancements in targeted therapies. Dr. Oh outlines breakthroughs in precision treatments, including PARP inhibitors for patients with BRCA mutations and the innovative LU-177-PSMA therapy, a “smart bomb” approach that targets cancer cells with remarkable specificity. He also explores the promise of immunotherapy, though he acknowledges its limited applicability for prostate cancer due to the disease's low mutational burden. The role of artificial intelligence in precision oncology is another key topic. Dr. Oh and Karan discuss how AI and machine learning are helping clinicians process complex data, from imaging to genomic profiles, to guide more informed treatment decisions. Dr. Oh envisions AI as an essential tool for streamlining oncology workflows while preserving the human connection between doctors and patients. Karan highlights the importance of effective communication in prostate cancer care, referencing a recent editorial co-authored by Dr. Oh. Together, they explore the need for more patient-centered terminology, such as replacing the term “castration-resistant prostate cancer” with “androgen deprivation-resistant prostate cancer,” to foster better understanding and improve patient experience. The episode concludes with a forward-looking discussion on clinical trials, the integration of new technologies like liquid biopsies, and the ongoing efforts to expand insurance coverage for biomarker testing. Dr. Oh emphasizes the critical role of collaboration, awareness, and education in advancing precision medicine and ensuring that patients benefit from the latest innovations. With Karan's thoughtful questions and Dr. Oh's expertise, this episode offers a comprehensive and accessible exploration of how precision medicine is reshaping the future of prostate cancer care. We hope you'll tune in to the series and share this important episode with others!
Have you checked out the AUA/ASTRO/SUO's recently released guidelines for salvage therapy in prostate cancer biochemical recurrence? In this episode of the BackTable Urology Podcast, guest Dr. Todd Morgan from the University of Michigan and host Dr. Aditya Bagrodia continue with part two of our series on prostate cancer biochemical recurrence management. --- This podcast is supported by: Veracyte https://www.veracyte.com/decipher --- SYNPOSIS The doctors focus on the difficulty in declaring a patient 'cured' and the implications of biochemical recurrence after treatment. Dr. Morgan highlights the importance of PSA in the postoperative setting and explores the role of the Decipher Prostate Genomic Classifier in personalizing treatment. He talks through the latest AUA/ASTRO/SUO consensus on biochemical recurrence guidelines, including the significance of early salvage therapy and the integration of advanced imaging techniques like PSMA PET scans. Further, Dr. Morgan emphasizes the role for multidisciplinary evaluation, patient counseling, and future directions of research to refine treatment options. This discussion underscores the transition from adjuvant to early salvage radiation as a standard practice and considers emerging biomarker strategies to inform treatment decisions. --- TIMESTAMPS 00:00 - Introduction 03:41 - Consensus Biochemical Recurrence Guidelines 08:56 - Evolution of Post-Prostatectomy Biochemical Recurrence Management 13:24 - Patient Counseling and Risk of Recurrence 17:42 - PSMA PET Scans 20:44 - Postoperative PSA Monitoring 28:35 - The Role of Radiation 31:56 - Hormone Therapy 39:00 - Salvage Lymphadenectomy 46:30 - Future Directions and Concluding Thoughts --- RESOURCES Veracyte https://www.veracyte.com/ Salvage Therapy for Prostate Cancer: AUA/ASTRO/SUO Guideline (2024) https://www.auanet.org/guidelines-and-quality/guidelines/salvage-therapy-for-prostate-cancer
Biochemical recurrence of prostate cancer can be difficult to diagnose and treat. In this episode of BackTable Urology, where Dr. Aditya Bagrodia hosts Dr. Amar Kishan, a genitourinary radiation oncologist at UCLA, to discuss the complexities of biochemical recurrence and local failure after radiation therapy for prostate cancer. --- This podcast is supported by: Veracyte https://www.veracyte.com/decipher --- SYNPOSIS First, they evaluate alternatives to androgen deprivation therapy (ADT), the benefits and risks associated with ADT, and the role of genetic classifier tests. They also detail the goals of prostate-specific antigen (PSA) monitoring, PSA trends post-radiation, and advancements in PSMA PET scans. Then, the conversation highlights modern treatment options like targeted radiation, low dose rate brachytherapy, salvage radical prostatectomy, and focal therapy. Finally, the doctors emphasize personalized and multidisciplinary treatment plans as they hope to improve long-term outcomes for patients with prostate cancer. --- TIMESTAMPS 00:00 - Introduction 04:31 - PSA Levels Post-Radiation 13:21 - Local Recurrence and PSMA PET 21:29 - Explaining Radiation Effects to Patients 22:41 - Managing PSA Bounce 26:05 - Imaging and Biopsy Techniques 28:55 - Treatment Options for Local Recurrence 30:16 - Re-Irradiation and Focal Therapy 33:13 - Concluding Thoughts --- RESOURCES Veracyte https://www.veracyte.com/
JCO PO author Dr. Amar U. Kishan, Professor, Executive Vice Chair, and Chief of Genitourinary Oncology Service in the Department of Radiation Oncology at the University of California, Los Angeles, shares insights into his JCO PO article, “Transcriptomic Profiling of Primary Prostate Cancers and Nonlocalized Disease on Prostate-Specific Membrane Antigen Positron Emission Tomography/Computed Tomography: A Multicenter Retrospective Study.” Host Dr. Rafeh Naqash and Dr. Kishan discuss the relationship between Decipher genomic classifier scores and prostate-specific membrane antigen (PSMA) PET/CT-based metastatic spread. TRANSCRIPT Dr. Rafeh Naqash: Hello and welcome to JCO Precision Oncology Conversations, where we bring you engaging conversations with authors of clinically relevant and highly significant JCO articles. I'm your host, Dr. Rafeh Naqash, Assistant Professor at the OU Health Stephenson Cancer Center at the University of Oklahoma. Today we are joined by Dr. Amar Kishan, Executive Vice Chair of the Department of Radiation Oncology at the David Geffen School of Medicine at UCLA and UCLA Jonsson Comprehensive Cancer Center, and also the corresponding and senior author of the JCO Precision Oncology article entitled, “Transcriptomic Profiling of Primary Prostate Cancers and Non Localized Disease on Prostate-Specific Membrane Antigen (PSMA) Positron Emission Tomography/Computed Tomography: A Multicenter Retrospective Study.” Dr. Kishan, welcome to our podcast and thank you for joining us today. Dr. Amar Kishan: Thank you so much for that kind introduction and the invitation to be here today. Dr. Rafeh Naqash: Well, it seems to me that there's a theme that people in the GU space, investigators in the GU space, are very interested in trying to understand risk predictors for prostate cancer. We had somebody, I believe from Huntsman Cancer Center a few months back on a previous podcast, where they were trying to do risk prediction modeling as well. Could you tell us why that's something that the GU community is very interested in? What's the background? Is it because there's no risk prediction approaches currently? And would this somehow influence management in the near future? Dr. Amar Kishan: Yeah, that's a great question. So, I think this goes back to the point that we're in the era of precision medicine now, and many cancers have these molecular stratification scores and all that. Prostate cancer has lagged a little bit behind in that regard, despite the fact that it's such a common cancer that affects so many people across the country and across the world. So, we do have risk stratification schemes for prostate cancer. These are based off clinical and pathologic variables, like the level of PSA, the size of the tumor on digital rectal examination, now, we're incorporating MRI imaging as well, and then what the cancer looks like under the microscope, the Gleason score. And now there have been revisions to the Gleason score, but it's really kind of the architecture, what the biopsy looks like. And this was kind of developed many, many years ago by Donald Gleason, a pathologist at the VA. What we're not necessarily taking into account routinely is kind of the biology of the cancer per se. You know, what are the molecular drivers? How could that influence ultimate outcome? And that's very important because we have these risk groups, low risk, very low risk, favorable intermediate risk, unfavorable intermediate risk, high risk, very high risk. But within each of those groups, based on the clinical kind of pathological characteristics, there's a huge heterogeneity in outpatients too, and our treatments are effective, but they can be morbid. Putting someone on hormone therapy for an extended period of time has a lot of side effects. Dose escalating radiotherapy or doing surgery and then radiation afterwards, these are big things that have a big impact on the patient, and I think we really need better risk stratification tools to understand who needs intensification and who we can de-escalate treatment for. Dr. Rafeh Naqash: I think those are absolutely valid points, perhaps not just for prostate cancer, more so for all cancers that we currently treat, especially in the current day and age, where we have a tendency to add more and more therapies, combination therapies for patients, and as you mentioned, risk stratification to help identify high risk versus low risk, where you can de intensify treatment, is of high value from a patient standpoint as well as from a financial toxicity standpoint. So then, going to this next part of the approach that you used, and from what I understand in this paper, you had the radiological aspect, which is the PSMA PET, which we'll talk about. Then you had the genomic aspect, where you did some genomic risk-based stratification. Then you had the transcriptomic score based on the Decipher score. So, could you go into some of the details, first, for the PSMA PET, when is it used? What is the utilization? What is it based on, the science behind the PSMA PET? And then we can talk about some of the other genomic transcriptomic predictors that you use in this study. Dr. Amar Kishan: Sure. Absolutely. So, a PSMA PET is an advanced molecular imaging tool. PSMA stands for prostate specific membrane antigen. It's a membrane protein that is expressed on the surface of prostate cancer cells. It is expressed elsewhere in the body as well. The utilization of this for imaging has been a revolution in the staging of prostate cancer, both upfront and in the recurrent setting. We basically had fairly recent approval for PSMA PET being used more routinely in upfront staging and recurrent staging in 2022. Essentially, what this is it gives us an ability to detect whether prostate cancer has spread at a time of diagnosis or try to localize the recurrence. Now, no imaging test is perfect, of course, and a PET has a resolution of about 3 mm. There are questions about the sensitivity of the PET. You get it on a patient with high-risk disease, the PET is negative; you do surgery, there are positive lymph nodes. That can happen, but it's far superior to the tools that we have had before. For instance, beforehand, all we would have is a contrast enhanced CT, bone scan, and MRI. And the sensitivity of those is far below that of a PSMA PET. And that has actually been shown in a randomized trial called the ProPSMA trial out of Australia, where they compared conventional upfront imaging versus PSMA upfront imaging with a crossover design, and there was better detection of disease with the PSMA PET. So that's been a revolution in how we stage prostate cancer. But I'm sure many of your listeners and others are aware of the concerns. When you get a new test and you're detecting disease that's extra prostatic, for instance, are you seeing truly significant new disease that we do need to change our management for, or are we just seeing stuff that wasn't there before that actually wouldn't impact anything? And what I mean by that is, let's say you're seeing things that would never have made a difference to the patient, but now you're saying they have metastatic disease. You're changing their entire treatment paradigm, all kinds of things like that. There's implications to this that hasn't been fully fleshed out. But very recently, like we're talking in July of 2024, essentially, there was a Lancet Oncology paper that looked at the long-term prognosis of patients who had extra prostatic disease on PSMA PET, judged by something called a PROMISE score, kind of gives a quantification on the volume of disease, the brightness of disease, and they correlated that with long term outcomes. And that was really the first time that we have long term follow up data that this extra prostatic disease on PSMA PET actually is prognostically important. So, we're getting there. I mean, now that it's approved and, in some sense, the cat is out of the bag, patients are coming in asking for a PSMA PET, etc. I'm sure everyone has experienced that, but I think we now do have good evidence that it actually is prognostically important as well. Dr. Rafeh Naqash: Thank you for that explanation. And again, to put this into context for things that I've seen and that might also help the listeners in other tumors, so, for example, melanoma surveillance tends to be or while on treatment, patients tend to have more PET scans than what you see, maybe in individuals with lung cancer, where you get a baseline PET and then you have follow up CT scan based imaging is that something that you guys have shifted from in the prostate cancer space with the approval for PSMA PET, where follow up imaging, whether patient is on treatment or surveillance imaging, is PSMA PET based? Dr. Amar Kishan: Yeah, that's a good question. I think there's actually less robust data to support it as a means of treatment response. But in terms of evaluating a recurrence, then, yes, that has become kind of a standard tool. It's very complicated because all of the metrics that we have for, say, a treatment failing are based on conventionally detected metastases or something that shows up on a CT or bone scan. So, again, that question arises if someone is on systemic therapy and then you see something on a PSMA PET, are you going to abandon the therapy that you're on? It technically would be earlier than you would otherwise have done that, or what are you going to do? So, that hasn't been fully fleshed out, but it is used in that circumstance. So, I'd say less for treatment monitoring and more for evaluation of suspected recurrence. Dr. Rafeh Naqash: Understood. And I'm guessing, as a futuristic approach, somebody out there may perhaps do a trial using PSMA PET based imaging to decide whether treatment change needs to be made or does not need to be made. Dr. Amar Kishan: Yeah. It is being incorporated into trials as we speak, I think. Dr. Rafeh Naqash: Now, going to the second part of this paper is the Decipher score. Could you explain what the score is, what its components are, how it's calculated? Is it DNA, is it RNA, is it both combined? Is it tissue based; is it blood based? Dr. Amar Kishan: Yeah. So, the Decipher is also an approved test now, was approved in 2018. What it is, essentially, and how it's derived is based on the idea originally that patients might have a recurrence after surgery for prostate cancer. And it's just a PSA recurrence. It's this way. It's literally what we call a biochemical recurrence. That patient might not have any problems, whereas other patients with a recurrence might go on to develop metastatic disease. And we didn't have a good way of determining which patient is which. Get back to that prognostic problem that we have. So, some investigators, they looked at men that had radical prostatectomy from 1987 to 2001 at the Mayo Clinic that had archived tissue. They looked at FFPE, or basically paraffin embedded tissue. They extracted the RNA and then did a microarray analysis and looked at transcriptomic signatures and wanted to see, could this discern the patients who had mets, who had clinically significant recurrences from those that didn't? And out of that exercise came the Decipher Genomic Classifier, which basically is based on 22 genes. These are involved with cell proliferation, etc., but it's an RNA-based, tissue-based assay. So, if you wanted to order a Decipher on somebody, you would need to use a biopsy or prostatectomy specimen to do so. Essentially, that the samples, they would take the highest grade, highest Gleason grade specimen, send it to their lab. Their main lab is in California. The company is called Veracyte. And then they will do this RNA express analysis with a microarray and then return a score. The score is 0 to 1. Basically, 0 is the lowest, one is the highest, and it is a way of prognosticating the risk of metastasis. Originally, when you get a Decipher report, it actually will tell you the 5 and 10-year risks of distant metastasis, and we'll quantify that. Dr. Rafeh Naqash: And you said this is approved or has been approved in 2018. So, is this insurance reimbursable at this point? Dr. Amar Kishan: Most insurances do, not all, and the criteria for getting it can vary, so we can talk about it, but it was initially developed in this post-op setting. On the basis of a significant amount of validation studies, it has been moved to being used in the upfront setting as well. So, if you look at some of the ongoing NRG trials, for instance, they are stratifying patients based off the upfront Decipher score. And this is based off of validation studies that have been conducted looking at past RTOG trials and other trials. That said, sometimes it is not approved by commercial insurances in the upfront setting, because that wasn't where it was initially validated and derived. But honestly, here in 2024, that's very uncommon. It's much more common that it's approved. Dr. Rafeh Naqash: Understood. And in your practice, or the medical oncologist practice at your institution or other institutions, is this something that is commonly used for some sort of treatment decision making that you've seen? Dr. Amar Kishan: Yeah. So, as a radiation oncologist, I do think it's a useful test, because my approach is, if we're talking about adding hormone therapy, for instance, which is oftentimes dominating the conversation, we know that it offers a relative benefit to a lot of patients. We've published on this; others have published on it. Let's say it reduces the chance of metastasis by about 40%. 10-year risk of metastasis has a ratio of 0.6. So, 40% reduction. But if your risk of metastasis is 2%, that benefit is not that much in absolute terms. And we don't historically have a great way of saying, what is your absolute risk of metastasis? And I think Decipher is one tool that does tell us that - it literally gives it on the report. Now, is that a holy grail? Is it 100% accurate? Nothing is 100% accurate. But it does give us some quantification. Then I can go back to the patient and say, yes, you will get a benefit from adding hormone therapy, but you're talking about going from 2% to 1%, and so they can decide if that's worth it to them. Conversely, it could be a situation where they really don't want hormone therapy, but it comes back that their risk of metastasis is 20%, and then there's actually a big absolute benefit. So that's how I use it as a radiation oncologist, and we would use it upfront. Now surgeons, and if I was consulting on a post operative patient, maybe it plays more of a role. And do we need to do post operative radiotherapy on this patient, or do we need to add hormone therapy in the postoperative situation? From the medical oncology perspective, there are emerging data that may be useful in the choice of systemic therapy for metastatic disease, but that is a little bit earlier in the investigational stage, I would say. So, when I'm working with medical oncologists, it's often still in this localized setting, and typically, do we add hormone therapy or not, and that type of thing. Dr. Rafeh Naqash: Understood. And from a reporting standpoint, so the Decipher score, I'm guessing it's some sort of a report that comes back to the ordering physician and you basically see the score, it gives you a potential recurrence free survival percentage or a metastasis percentage of what is your risk for having metastasis in the next five years - is that how they generally do it? Because I've personally never seen one, so I'm just curious. Dr. Amar Kishan: Yeah, essentially, it comes back with a score, a numerical score, again, from 0 to 1, and it will basically give you the five-year risk of distant metastasis. The ten-year risk of distant metastasis. You can request an extended report that provides additional, not as well supported signatures that are out there, like ADT response signature, etc. But those maybe may have been published, but are not clinically validated as much, but the actual Decipher report, which goes to patients too, just has this kind of 5,10-year risk of distant metastasis. They have some estimations on prostate cancer specific mortality as well. Dr. Rafeh Naqash: Sure. Now, the third part of this project, and correct me if I'm wrong, the grid database of the 265 genomic signature score. From what I understood, this is a different component than the Decipher score. Is that a fair statement? Dr. Amar Kishan: Yeah. No, that's exactly correct. And that was an exploratory part of this analysis, to be honest. Basically, I think our main focus in the paper was those advances that we've talked about PSMA and Decipher, those happened concurrently. People started developing PSMA PET, people started developing Decipher. And so, what we wanted to understand was, if you have a patient that has extra prosthetic disease on PSMA PET, are those biologically more aggressive cancers, is their Decipher score going to be higher? What can we learn about the biology of this? And we were the first, to my knowledge, where we actually had a large data set of patients that actually received PSMA PETs and Decipher. And that's kind of the gist of the paper. We have patients in the upfront setting, patients in the post radical prostatectomy setting, and we're essentially showing that there is this correlation. In the upfront setting, the odds of extra prosthetic disease are higher for higher Decipher scores, which is kind of maybe validating that this biology is capturing something that's akin to this ability to spread. And in the post-op setting, because we have time to failure, technically, we can calculate a hazard ratio rather than odds ratio. So, we have a hazard ratio that's significantly associated with an increased risk of spread for patients with higher Decipher. The grid portion, which is the genomic resource information database, was more of an exploratory part where I mentioned the Decipher score is based off this microarray, they're looking at 1.4 million transcripts. Only 22 are part of the Decipher, but you can request the rest of the signature data as well. And so, we wanted to look at other pathways, other signatures that have been published, like looking at DNA repair, neuroendocrine pathway, just to see if we could see any correlations there that's not necessarily as clinically actionable. These are more exploratory. But again, we were trying to just look at whether patients who had non localized disease on their PSMA PET, whether their primary had more aggressive biology. We did see that. So that's kind of loosely speaking things like PTEN loss, androgen receptor, DNA repair, metabolism, neuroendocrine signaling, which are thought to be portenders of aggressive disease. Those pathways were upregulated at the RNA level in patients who had non-localized disease. And that's kind of the take home from that. But I wouldn't say any of that is clinically actionable at this point. It's more kind of defining biology. Dr. Rafeh Naqash: Some of the interesting correlations that you make here, at least in the figures that we see, you're looking at different local occurrences, nodal metastases, M1A and M1B disease. And one thing that I'm a little curious about is the Decipher score seems to be lower in pelvic nodal metastasis, that is, PSMA PET positive versus local recurrence, which has a slightly higher Decipher score. Is that just because of a sample size difference, or is there a biologically different explanation for that? Dr. Amar Kishan: Yeah, that's a good point. I would assume that's probably because of a sample size in this case, and it's a little bit complicated. It wasn't statistically different. And it was 0.76 on average for patients with local recurrence and 0.7 for patients with a pelvic nodal metastasis. Well, what I think is interesting is we can maybe think that in this post-op setting the time to failure could have been long in some of these cases. So, it is conceivable that an isolated nodal recurrence 10 years after the surgery, for instance, is not as aggressive a cancer as a local recurrence in a short time after the surgery. And that's not taken into account when you're just looking at median scores like we are in this fox and whiskers plot. But overall, I think what it's suggesting is that there are patients who have more indolent disease. That's actually pretty widespread there. There are pretty indolent cases that have these nodal metastases. So just because you have a nodal metastasis doesn't mean it's an incredibly aggressive cancer, biologically. Dr. Rafeh Naqash: Now, the exploratory component, as you mentioned, is the grid part where you do look at TP53, which is a cell cycle gene, and higher TP53 associated with worse recurrences, from what I understand. Do you see that just from a cell cycle standpoint? Because from what I, again, see in the paper, there's a couple of other cell cycle related signatures that you're using. Is that just a surrogate for potential Gleason score? Have you guys done any correlations where higher Gleason score is associated with maybe higher cell cycle checkpoint, pathway related alterations and replication stress and DNA damage and perhaps more aggressive cancers? Dr. Amar Kishan: Yeah, that's a great question. We haven't done that in this paper, but it has been published before that there is this correlation loosely between grade and some of these parameters - so repair, metabolism, androgen receptor signaling. However, it's a very great point that you bring up, which is that it's pretty heterogeneous and that's why we need something like this as opposed to Gleason score. So, you can have Gleason 10 cancer. I mean, that would be pretty uncommon. But within the Gleason 9, at least, which we have published on and looked at, there's a heterogeneity. There are some that are biologically not that aggressive. And the converse Gleason 7, you can have some that are actually biologically aggressive. That's why it may be useful to move away from just the pathological architecture and get a little bit more into some of these pathways. Dr. Rafeh Naqash: What's the next step here? I know this perhaps isn't ready for primetime. How would you try to emphasize the message in a way that makes it interesting and clinically applicable for your colleagues in the GU community? Dr. Amar Kishan: Yeah. I think for me, what I would try to emphasize here and what I think is the main takeaway is this is kind of a validation that having extra prostatic disease on PSMA PET is likely suggestive of a more aggressive disease biology. And I think what this stresses to me is the importance of getting a PSMA PET, particularly in patients with high-risk prostate cancer. This isn't always happening. And I think if we see things on a PSMA PET, we really need to consider systemic therapy intensification. And what do I mean by that as a practical point? You have a high-risk prostate cancer patient. You get a PSMA PET, you see an isolated pelvic lymph node. If we believe the results of the study, that's a more aggressive biology likely. Whether we have the Decipher or whether we have genomic signatures, which we may or may not have, maybe that patient should get treated with something like an androgen receptor signaling inhibitor in addition to ADT, more akin to a clinically node positive case. So, intensify the systemic therapy, more aggressive disease. That's how I would incorporate it practically into my practice, that really what we're seeing on the PSMA PET is real. It's a reflection of biology that's aggressive. It's not just some Will Rogers effect where you're upstaging stuff needlessly. I think this is telling us some true biology. So that's kind of what my takeaway would be. I think future areas of investigation would be, honestly, to try to have a better idea of what's going on in these metastases. So, if you could design a study potentially, where your biopsy some of these and actually do sequencing and understand a little bit more of that. And so, we're looking into stuff like that. But my takeaway for like the everyday clinician would be to try to get a PSMA PET, if you can, and to intensify therapy on the basis of that, or at least consider it, discuss it in a multidisciplinary setting. Dr. Rafeh Naqash: And I'm guessing somebody out there, perhaps even you, are thinking or planning on doing a ctDNA MRD based correlation here, since that's up and coming in this space. Dr. Amar Kishan: That is up and coming, I think one of the challenges in prostate cancer is the amount of ctDNA can be low. But yes, you're right, that's certainly things that a lot of us are looking at, too. Dr. Rafeh Naqash: Excellent. Well, thank you for the science discussion, Dr. Kishan, could you tell us a little bit about yourself, your career trajectory, where you started, what you're doing, and perhaps some advice for early career junior investigators, trainees, things that might have worked for you, that could also work for them as they are progressing in their careers. Dr. Amar Kishan: Sure. So, yeah, I'm a radiation oncologist at UCLA. I run the prostate cancer radiation program. Clinically. I'm also heavily involved in our research enterprise, so I kind of oversee the clinical and translational research aspect. That's what I do currently. So, I did my residency in radiation oncology at UCLA. Just on a personal note, my wife is from LA, her parents live in LA. We really wanted to stay in LA, so I was fortunate to be able to join the faculty here. I always liked GU oncology, so that was kind of a natural thing for me to kind of go into this position here and try to build the GU program. I've been very fortunate to have great collaborators. My message to students and trainees is to try to reach outside your department for mentorship as well. It's important to have people inside your department who can mentor you. But as a radiation oncologist, I work so closely with urology, so closely with medical oncology that I'm very fortunate to have individuals in those departments who have a vested interest in me and my success as well. I like working with them. It's important to be a team player. If they need help, you help them. If you need help, you ask for help from them. So, I think that's the single biggest thing that I would say to any trainee is don't be intimidated. Please reach outside of your department. Lots of people are willing to help and provide mentorship, and it's helpful to have that perspective. We are in a very multidisciplinary environment and era of practicing medicine. Dr. Rafeh Naqash: Well, thank you again for those personal insights and especially for submitting your work to JCO PO. And we hope to see more of this work perhaps in the subsequent sessions for JCO PO, and maybe we'll bring you back again. And at that point, the Decipher and the PSMA PET scan will have more data, more implementation in the clinically relevant real-world setting. Dr. Amar Kishan: Thank you very much. And if I could just give one quick shout out. The first author of this work, which I presented, was Dr. John Nikitas, who is a trainee that works with me here at UCLA a PGY5 resident. So, I do want to give credit to him as well. Dr. Rafeh Naqash: And John, if you're listening to this hopefully, it's always great to get a shout out from your mentor. Thank you both again for putting in the work and effort to submit this manuscript. Thank you for listening to JCO Precision Oncology Conversations. Don't forget to give us a rating or review and be sure to subscribe so you never miss an episode. You can find all ASCO shows at asco.org/podcasts. The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Disclosures Dr. Kishan Honoraria Company: Varian Medical Systems, Boston Scientific, Janssen Oncology Consulting or Advisory Role Company: Janssen, Boston Scientific, Lantheus Research Funding Company: Janssen , Point Biopharma
Dr. Daniel Kwon interviews Dr. Peter Choyke, a leading expert in molecular imaging and nuclear medicine, about the recent advancements in the use of PSMA PET imaging for prostate cancer. Check out more articles on this topic Prostate Cancer Special Collection
How to use Prostate-Specific Membrane Antigen-Positron Emission Tomography/CT in the Management of Relapsing Prostate Cancer Patients following Local Therapy with Curative Intent CME Available: https://auau.auanet.org/node/41124 At the conclusion of this activity, participants will be able to: 1. Identify the clinical scenario in which PSMA PET/CT is most helpful to identify the localization and extent of locoregional or systemic metastatic disease. 2. Identify the pitfalls of false-positive and false-negative PSMA PET/CT findings. 3. Apply the findings of PSMA PET/CT for the best individual therapeutic approach. 4. Identify patients with radiorecurrent organ-confined prostate cancer. 5. Identify those patients who are candidates for local therapy of oligometastatic disease in relapsing prostate cancer. ACKNOWLEDGEMENTS This educational activity is supported by independent educational grants from: Astellas, Janssen Biotech, Inc., administered by Janssen Scientific Affairs, LLC, Lantheus Medical Imaging, Merck & Co., Inc., Novartis Pharmaceuticals Corporation, Pfizer, Inc.
Positron Emission Tomography (PET) combined with Computed Tomography (CT) is a powerful imaging modality used in oncology for diagnosis, staging, and treatment monitoring. However, one limitation of PET/CT is the need for accurate attenuation correction (AC) to account for tissue density variations. Traditionally, low-dose CT scans are used for AC, but these contribute to patient radiation exposure. In a new study, researchers Kevin C. Ma, Esther Mena, Liza Lindenberg, Nathan S. Lay, Phillip Eclarinal, Deborah E. Citrin, Peter A. Pinto, Bradford J. Wood, William L. Dahut, James L. Gulley, Ravi A. Madan, Peter L. Choyke, Ismail Baris Turkbey, and Stephanie A. Harmon from the National Cancer Institute proposed an artificial intelligence (AI) tool to generate attenuation-corrected PET (AC-PET) images directly from non-attenuation-corrected PET (NAC-PET) images, reducing the reliance on CT scans. Their research paper was published in Oncotarget's Volume 15 on May 7, 2024, entitled, “Deep learning-based whole-body PSMA PET/CT attenuation correction utilizing Pix-2-Pix GAN.” Full blog - https://www.oncotarget.org/2024/07/11/ai-for-improved-pet-ct-attenuation-correction-in-prostate-cancer-imaging/ Paper DOI - https://doi.org/10.18632/oncotarget.28583 Correspondence to - Stephanie A. Harmon - stephanie.harmon@nih.gov Video short - https://www.youtube.com/watch?v=0mZItCB8AtI Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28583 Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/ Keywords - cancer, deep learning, PSMA PET, attenuation correction About Oncotarget Oncotarget is an open-access, peer-reviewed journal that has published primarily oncology-focused research papers since 2010. These papers are available to readers (at no cost and free of subscription barriers) in a continuous publishing format at Oncotarget.com. Oncotarget is indexed and archived by PubMed/Medline, PubMed Central, Scopus, EMBASE, META (Chan Zuckerberg Initiative) (2018-2022), and Dimensions (Digital Science). To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us: Facebook - https://www.facebook.com/Oncotarget/ X - https://twitter.com/oncotarget Instagram - https://www.instagram.com/oncotargetjrnl/ YouTube - https://www.youtube.com/@OncotargetJournal LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/ Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVh MEDIA@IMPACTJOURNALS.COM
Check out this week's QuadCast as we highlight the benefit of immunotherapy for nasopharynx cancer, new ASTRO guidelines for HPV+ oropharynx cancer treatment, the benefits of surgery for low grade serous ovarian cancer, the potential of PSMA PET to help with recurrent GBM, and more. Check out the website and subscribe to the newsletter! www.quadshotnews.com Founders & Lead Authors: Laura Dover & Caleb Dulaney Podcast Host: Sam Marcrom
Host: Jennifer Caudle, DO Guest: Geoffrey B. Johnson, M.D., Ph.D. Prostate-specific membrane antigen (PSMA) PET scans are a method by which clinicians can see if a patient who is suffering from prostate cancer has tumors that are expressing the PSMA target. In addition to that, the scan allows us to measure how much of the medication we get onto that cancer target and if it's going to be effective. Take a deep dive with Dr. Jennifer Caudle as she speaks with Dr. Geoffrey Johnson, Nuclear Medicine Specialist and Radiologist at the Mayo Clinic in Rochester, Minnesota, who also presented this research at the Society of Nuclear Medicine and Molecular Imaging 2024 Annual Meeting.
Host: Jennifer Caudle, DO Guest: Geoffrey B. Johnson, M.D., Ph.D. Prostate-specific membrane antigen (PSMA) PET scans are a method by which clinicians can see if a patient who is suffering from prostate cancer has tumors that are expressing the PSMA target. In addition to that, the scan allows us to measure how much of the medication we get onto that cancer target and if it's going to be effective. Take a deep dive with Dr. Jennifer Caudle as she speaks with Dr. Geoffrey Johnson, Nuclear Medicine Specialist and Radiologist at the Mayo Clinic in Rochester, Minnesota, who also presented this research at the Society of Nuclear Medicine and Molecular Imaging 2024 Annual Meeting.
As part of the 2024 Prostate Cancer Patient Conference, Dr. Thomas Hope presents information on PSMA-PET and discusses imaging in the evaluation of biochemical recurrence in prostate cancer. Series: "Prostate Cancer Patient Conference" [Health and Medicine] [Show ID: 39762]
As part of the 2024 Prostate Cancer Patient Conference, Dr. Thomas Hope presents information on PSMA-PET and discusses imaging in the evaluation of biochemical recurrence in prostate cancer. Series: "Prostate Cancer Patient Conference" [Health and Medicine] [Show ID: 39762]
As part of the 2024 Prostate Cancer Patient Conference, Dr. Thomas Hope presents information on PSMA-PET and discusses imaging in the evaluation of biochemical recurrence in prostate cancer. Series: "Prostate Cancer Patient Conference" [Health and Medicine] [Show ID: 39762]
As part of the 2024 Prostate Cancer Patient Conference, Dr. Thomas Hope presents information on PSMA-PET and discusses imaging in the evaluation of biochemical recurrence in prostate cancer. Series: "Prostate Cancer Patient Conference" [Health and Medicine] [Show ID: 39762]
As part of the 2024 Prostate Cancer Patient Conference, Dr. Thomas Hope presents information on PSMA-PET and discusses imaging in the evaluation of biochemical recurrence in prostate cancer. Series: "Prostate Cancer Patient Conference" [Health and Medicine] [Show ID: 39762]
Check out this week's QuadCast where we highlight the benefits of PSMA PET, how CPAP can help breast cancer radiation treatments, and more. Check out the website and subscribe to the newsletter! www.quadshotnews.com Founders & Lead Authors: Laura Dover & Caleb Dulaney Podcast Host: Sam Marcrom
Editor-in-Chief Sue Yom co-hosts with Dr. Thomas Zilli, Associate Editor at the Red Journal and Professor and Director of the Department of Radiation Oncology at the Oncology Institute of Southern Switzerland. Dr. Zilli was co author on Prostate Bed Delineation Guidelines for Postoperative Radiation Therapy: On Behalf Of The Francophone Group of Urological Radiation Therapy, published in the April 2021 issue of the Red Journal. Guests include Dr. Alan Dal Pra, Associate Professor and Director of Clinical Research in the Department of Radiation Oncology at the University of Miami, who first authored the ESTRO ACROP 2023 guideline and with colleagues at UCLA has worked on patterns of prostate bed recurrence on PSMA-PET in relation to the RTOG guidelines, as well as Dr. Floor Staal, PhD candidate at the University of Groningen, who is focused on the study of salvage radiotherapy treatment and is coordinator of the PSMA-PET Guided Hypofractionated Salvage Prostate Bed Radiotherapy (or PERYTON) trial. She first authored an article publishing this month, PSMA PET/CT based clinical target volume delineation guideline for postprostatectomy salvage radiation therapy: the PERYTON-Guideline.
The AUA Expert Exchange Podcast: Discussions in Managing GU Cancer: Novel Imaging for Genitourinary Cancers - Diagnostics and Theranostics CME Available: https://auau.auanet.org/node/39411 Release Date: December, 2023 Expiration Date: December, 2024 LEARNING OBJECTIVES At the conclusion of this activity, participants will be able to: 1. Review the latest clinical trials investigating the use of PET imaging agents in prostate, kidney, and urothelial cancer, including their diagnostic accuracy and impact on patient management. 2. Discuss the available PET imaging agents for prostate cancer, with a specific focus on PSMA (Prostate-Specific Membrane Antigen) PET imaging, including its mechanism of action and its potential for detection of primary tumors, lymph node metastases, and distant metastases. 3. Discuss the benefits of incorporating PET imaging, including PSMA PET, in guiding treatment decisions for GU cancers, such as its impact on treatment selection, treatment response assessment, and the potential for theranostic approaches. ACKNOWLEDGEMENTS: Support provided by independent educational grants from: Astellas and Pfizer, Inc AstraZeneca Janssen Biotech, Inc., administered by Janssen Scientific Affairs, LLC Lantheus Medical Imaging Merck & Co., Inc.
In our next episode, we are joined by Dr. Sanjay Patel, a urologic oncologist from the Stephenson Cancer Center at the University of Oklahoma, who also happens to be Vivek's older brother! We discuss the management of prostate cancer from the perspective of our urology colleagues. As medical oncologists, these are conversations and decisions that we are almost never a part of, as they are being had often before patients ever see us. It was so helpful to get to hear how Dr. Patel thinks about his patients! Content: - What considerations go into determining if a patient is a good candidate for a prostate biopsy? -What is the role of an MRI in the workup?-What are the steps involved in a biopsy?-When is additional imaging (such as PSMA PET) needed? -How does he decide surgery vs. radiation referral in unfavorable intermediate risk patients? -When is pelvic lymph node dissection recommended? -What does active surveillance entail? -What about management of high risk and very high risk localized prostate cancer? ** Want to review the show notes for this episode and others? Check out our website: https://www.thefellowoncall.com/our-episodesLove what you hear? Tell a friend and leave a review on our podcast streaming platforms!Twitter: @TheFellowOnCallInstagram: @TheFellowOnCallListen in on: Apple Podcast, Spotify, and Google Podcast
From the use of prostate-specific membrane antigen (PSMA) positron-emission tomography (PET) to advancements in targeted treatments, prostate cancer care is quickly evolving. Edwin M. Posadas, MD, director of the Experimental Therapeutics Program and director of the Center for Urologic Oncology Research Excellence at Cedars-Sinai in Los Angeles, speaks with Robert A. Figlin, MD, the Steven Spielberg Family Chair in Hematology-Oncology at Cedars-Sinai, about how he is already implementing promising new data into practice. Although Dr. Posadas notes that although immunotherapy approaches in prostate cancer have been “a bit of a disappointment” so far, he sees “a lot of exciting research going on.” He explains why he doesn't “like to wait” when expanding his therapeutic armamentarium and why he prefers to be “proactive rather than reactive” when it comes to molecular profiling and other approaches.
Drs Sandhya Srinivas and Tanya B. Dorff discuss metastatic hormone-sensitive prostate cancer, which patients are the best candidates for doublets vs triplets, and how we pick these patients. Relevant disclosures can be found with the episode show notes on Medscape (https://www.medscape.com/viewarticle/988737). The topics and discussions are planned, produced, and reviewed independently of advertisers. This podcast is intended only for US healthcare professionals. Resources Prostate Cancer https://emedicine.medscape.com/article/1967731-overview Metastatic Hormone-Sensitive Prostate Cancer: Toward an Era of Adaptive and Personalized Treatment https://pubmed.ncbi.nlm.nih.gov/37220335/ Triplet or Doublet Therapy in Metastatic Hormone-Sensitive Prostate Cancer: Updated Network Meta-Analysis Stratified by Disease Volume https://pubmed.ncbi.nlm.nih.gov/37055323/ PSMA PET in Imaging Prostate Cancer https://pubmed.ncbi.nlm.nih.gov/35155262/ Risks and Cancer Associations of Metachronous and Synchronous Multiple Primary Cancers: a 25-Year Retrospective Study https://pubmed.ncbi.nlm.nih.gov/34556087/ The Promise of Metastasis-Directed Therapy for Oligometastatic Prostate Cancer: Going Beneath the Surface With Molecular Imaging https://pubmed.ncbi.nlm.nih.gov/35058322/ Gleason Score https://www.ncbi.nlm.nih.gov/books/NBK553178/ Luteinizing Hormone-Releasing Hormone (LHRH) Receptor Agonists Vs Antagonists: a Matter of the Receptors? https://pubmed.ncbi.nlm.nih.gov/23418666/ The Role of CYP17A1 in Prostate Cancer Development: Structure, Function, Mechanism of Action, Genetic Variations and Its Inhibition https://pubmed.ncbi.nlm.nih.gov/29372682/ Chemohormonal Therapy in Metastatic Hormone-Sensitive Prostate Cancer: Long-Term Survival Analysis of the Randomized Phase III E3805 CHAARTED Trial https://pubmed.ncbi.nlm.nih.gov/29384722/ Abiraterone for Prostate Cancer Not Previously Treated With Hormone Therapy https://pubmed.ncbi.nlm.nih.gov/28578639/ Abiraterone Plus Prednisone in Metastatic, Castration-Sensitive Prostate Cancer https://pubmed.ncbi.nlm.nih.gov/28578607/ Health-Related Quality of Life in Metastatic, Hormone-Sensitive Prostate Cancer: ENZAMET (ANZUP 1304), an International, Randomized Phase III Trial Led by ANZUP https://pubmed.ncbi.nlm.nih.gov/34928708/ Darolutamide and Survival in Metastatic, Hormone-Sensitive Prostate Cancer https://pubmed.ncbi.nlm.nih.gov/35179323/ Abiraterone Plus Prednisone Added to Androgen Deprivation Therapy and Docetaxel in De Novo Metastatic Castration-Sensitive Prostate Cancer (PEACE-1): a Multicentre, Open-Label, Randomised, Phase 3 Study With a 2 × 2 Factorial Design https://pubmed.ncbi.nlm.nih.gov/35405085/
This week on the BackTable Urology Podcast, Dr. Bagrodia talks with Dr. Daniel Spratt, professor and chairman of radiation oncology at Case Western University in Cleveland, about the workup and treatment of high risk prostate cancer. --- CHECK OUT OUR SPONSOR Veracyte https://www.veracyte.com/decipher --- SHOW NOTES First, Dr. Spratt defines high risk prostate cancer and discusses how to evaluate non-specific PSMA PET findings. He notes the importance of standardized systems to avoid over-calling such findings and discusses the role of CT scans and MRI scans when necessary. Finally, the doctors emphasize the importance of synthesizing PSMA PET findings into their decision-making. Next, the doctors discuss the use of germline and genomic testing, specifically Decipher testing, to characterize the tumor. Germline testing can determine eligibility for neoadjuvant PARP inhibitor trials, and biomarkers have the potential to improve radiation therapy outcomes. Although they quickly summarize the NCCN guidelines, they also emphasize the importance of patient counseling to determine the right treatment plan. Then, the doctors move on to discuss the different radiation treatments available for treating high-risk prostate cancer, such as conventional fractionation, brachytherapy, and ultrahypofractionated radiotherapy. They also explain the use of protons in treating high-risk prostate cancer, which is difficult because of the lack of high-level evidence and financial benefit when using protons compared to conventional radiation treatments. Finally, they wrap up the episode by explaining the correlation between early PSA responses and the success of radiation therapy. Surgery and radiation are often used together in treating most cancers, and how combining both can cut down the chances of PSA recurrence. --- RESOURCES Veracyte Decipher: https://decipherbio.com/
AUA2023: How to use PSMA-PET/CT in the Management of Relapsing Prostate Cancer Patients following Local Therapy with Curative Intent CME Available: https://auau.auanet.org/node/38312 CME Expiration Date: May, 2024 ACKNOWLEDGEMENTS Independent educational grant support provided by: Astellas AstraZeneca Janssen Biotech, Inc., administered by Janssen Scientific Affairs, LLC Lantheus Medical Imaging Merck & Co., Inc. Pfizer, Inc.
In this episode of ASCO Educational podcasts, we'll explore how we interpret and integrate recently reported clinical research into practice. Part One involved a 72-year old man with high-risk, localized prostate cancer progressing to hormone-sensitive metastatic disease. Today's scenario focuses on de novo metastatic prostate cancer. Our guests are Dr. Kriti Mittal (UMass Chan Medical School) and Dr. Jorge Garcia (Case Western Reserve University School of Medicine). Together they present the patient scenario (1:13), going beyond the one-size-fits-all approach (4:54), and thinking about the patient as a whole (13:39). Speaker Disclosures Dr. Kriti Mittal: Honoraria – IntrinsiQ; Targeted Oncology; Medpage; Aptitude Health; Cardinal Health Consulting or Advisory Role – Bayer; Aveo; Dendreon; Myovant; Fletcher; Curio Science; AVEO; Janssen; Dedham Group Research Funding - Pfizer Dr. Jorge Garcia: Honoraria - MJH Associates: Aptitude Health; Janssen Consulting or Advisor – Eisai; Targeted Oncology Research Funding – Merck; Pfizer; Orion Pharma GmbH; Janssen Oncology; Genentech/Roche; Lilly Other Relationship - FDA Resources ASCO Article: Implementation of Germline Testing for Prostate Cancer: Philadelphia Prostate Cancer Consensus Conference 2019 ASCO Course: How Do I Integrate Metastasis-directed Therapy in Patients with Oligometastatic Prostate Cancer? (Free to Full and Allied ASCO Members) If you liked this episode, please follow the show. To explore other educational content, including courses, visit education.asco.org. Contact us at education@asco.org. TRANSCRIPT Disclosures for this podcast are listed on the podcast page. Dr. Kriti Mittal: Hello and welcome to this episode of the ASCO Education Podcast. Today, we'll explore how we interpret and integrate recently reported clinical research into practice. In a previous episode, we explored the clinical scenario of localized prostate cancer progressing to metastatic hormone-sensitive disease. Today, our focus will be on de novo metastatic prostate cancer. My name is Kriti Mittal and I am the Medical Director of GU Oncology at the University of Massachusetts. I am delighted to co-host today's discussion with my colleague, Dr. Jorge Garcia. Dr. Garcia is a Professor of Medicine and Urology at Case Western Reserve University School of Medicine. He is also the George and Edith Richmond Distinguished Scientist Chair and the current Chair of the Solid Tumor Oncology Division at University Hospitals Seidman Cancer Center. Here are the details of the patient case we will be exploring: The patient also notes intermittent difficulty in emptying his bladder with poor stream for the last six months. A CT scan of the abdomen and pelvis demonstrates enlarged prostate gland with bladder distension, pathologically enlarged internal and external iliac lymph nodes, and multiple osteolytic lesions in the lumbar sacral, spine, and pelvic bones. A CT chest also reveals supraclavicular lymphadenopathy and sclerotic foci in three ribs. So this patient meets the criteria for high-volume disease and also has axial and appendicular lesions. The patient was admitted for further evaluation. A bone scan confirmed uptake in multiple areas identified on the CT, and a PSA was found to be greater than 1500. Biopsy of a pelvic lymph node confirmed the diagnosis of prostate cancer. This patient is somewhat different from the first case we presented in terms of timing of presentation; this patient presents with de novo metastatic high-volume disease, in contrast to the first patient who then became metastatic after undergoing treatment for high-risk localized disease. Would you consider these two cases different for the purposes of dosing docetaxel therapy when you offer upfront triplet therapy combinations? Dr. Jorge Garcia: That's a great question. I actually do not. The natural history of someone with localized disease receiving local definitive therapy progressing over time is different than someone walking in with de novo metastatic disease. But now, with the challenges that we have seen with prostate cancer screening, maybe even COVID, to be honest with you, in North America, with the late care and access to testing, we do see quite a bit of patients actually walking in the office with de novo metastatic disease. So, to me, what defines the need for this patient to get chemotherapy is the volume of his disease, the symptoms of his disease – to be honest with you – and the fact that, number one, he is clinically impaired. He has symptomatic disease, and he does have a fair amount of disease, even though he may not have visceral metastasis. Then his diseases give him significant pain. Oral agents are very good for pain control. I'm not disputing the fact that that is something that actually these agents can do. But I also believe I'm senior enough and old enough to remember that chemotherapy, when it works, can actually really alleviate pain quite drastically. So for me, I think that the way that I would probably counsel this patient is to say, "Listen, we can give you ADT plus an oral agent, but I really believe your symptomatic progression really talks about the importance of rapid control of your disease.” And based upon the charted data from the United States, and equally important, PEACE-1, which is the French version of ADT, followed by abiraterone, if you will, and certainly ARASENS is the standard of care for me for a patient like this will be triple therapy with ADT and docetaxel. What I think is important for us to remember is that, in ARASENS, it was triple therapy together. I am worried sometimes about the fatigue that patients can have during the first six cycles of docetaxel. So oftentimes, I tell them if they're super fit, I may just do triple therapy up front, but if they I think they're going to struggle, what I tell them is, "Hey, we're going to put you on ADT chemotherapy. Right after you're about to complete chemo, we'll actually add on the darolutamide." So I do it in a sequence, and I think that's part of the data; we just still don't know if it should be given three at front or ADT chemo, followed by immediately, followed by an ARI. So I love to hear if that's how you practice or you perhaps have a different thought process. Dr. Kriti Mittal: So I usually start the process of prior authorization for darolutamide the day I meet them for the first time. I think getting access to giving docetaxel at the infusion center is usually much faster than the few weeks it takes for the prior authorization team to get copay assistance for darolutamide. So, in general, most of my patients start that darolutamide either with cycle two or, depending on their frailty, I do tend to start a few cycles in like you suggested. I've had a few patients that I've used the layered-in approach, completing six cycles of chemotherapy first and then layering in with darolutamide. I think conceptually the role of intensifying treatment with an androgen receptor inhibitor is not just to get a response. We know ADT will get us a PSA response. I think the role of an androgen receptor inhibitor is to prevent the development of resistance. So, delaying the development of resistance will be pertinent to whether we started with cycle one, cycle six, or after. So, we really have to make decisions looking at the patient in front of us, looking at their ECOG performance status, their comorbidities, and frailty, and we cannot use a one-size-fits-all approach. Dr. Jorge Garcia: Yeah, I like that and I concur with that. Thank you for that discussion. I think that you may recall some of our discussions in different venues. When I counsel patients, I tell the patients that really the goal of their care is on the concept of the three Ps, P as in Peter. The first P is we want to prolong your life. That's the hallmark of this regimen, the hallmark of the data that we have. That's the goal, the primary goal of these three indications is survival improvement. So we want to prolong your life so you don't die anytime soon from prostate cancer. The second P, as in Peter, is to prevent, and the question is preventing what? We want to prevent your cancer from growing, from growing clinically, from growing radiographically, and from growing serologically, which is PSA and blood work. Now, you and I know and the audience probably realize that the natural history of prostate cancer is such that traditionally your PSA will rise first. There is a lead time bias between the rise and the scan changes and another gap in time between scans and symptoms. So it's often not the case when we see symptomatic disease preceding scans or PSAs, but sometimes in this case, it's at the same time. So that is the number one. And as you indicated, it's prevention of resistance as well, which obviously we can delay rPFS, which is a composite endpoint of radiographic progression, symptomatic progression, and death of any cause. But the third P is I called it the P and M, which is protecting and maintaining, and that is we want to protect your quality of life while we treat you. And we want to maintain your quality of life while we treat you. So to me, it's critically important that in addition of aiming for an efficacy endpoint, we don't lose sight of the importance of quality of life and the protection of that patient in front of us. Because, undoubtedly, where you get chemo or where you get an oral agent, anything that we offer our patients has the potential of causing harm. And I think it is a balance between that benefit and side effect profile that is so critically important for us to elucidate and review with the patient. And as you know, with the charted data, Dr. Alicia Morgans now at Dana-Farber, published a very elegant paper in JCO looking at the impact of docetaxel-based chemotherapy as part of the charted data in the North American trial and into quality of life. And we clearly define that your quality of life may go down a bit in the first few months of therapy, predictably because you're getting chemotherapy. But at the end of the six months, nine months, and certainly at the end of a year mark, the quality of life data for those who receive ADT and chemotherapy was far better than those who actually got ADT alone. Now, if you look at the quality of data for RSNs, a similar pattern will appear that although chemotherapy is tied to misconceptions of significant toxicity, in our hands, in good hands, and I think our community of oncology in North America are pretty familiar with the side effects and how to manage and minimize side effects on chemotherapy, I think it still requires a balance and a thoughtful discussion to make sure that we're not moving forward chasing a PSA reduction at the expense of the quality of life of the patient. So I think orchestrating that together with the patient as a team is critically important as well. Dr. Kriti Mittal: Thank you, Dr. Garcia. Moving on to the next concept we'd like to discuss in today's podcast the role of PARP inhibitors. Case Two was treated with androgen deprivation docetaxel and darolutamide. Consistent with current guidelines, the patient was also referred to germline testing and was found to be BRCA 2-positive. The patient's disease remained stable for 24 months, at which time he demonstrated disease progression, radiographically and clinically, and his disease was termed castration-resistant. There has been a lot published in the last few years regarding the role of PARP inhibitors in metastatic castration-resistant prostate cancer, or mCRPC. The PROfound trial led to the approval of olaparib in patients with deleterious mutations in HRR genes for those who had been treated previously with AR-directed therapy. The TRITON2 trial led to the approval of rucaparib in the same month for mCRPC patients with BRCA mutation for those patients who had previously been treated with AR inhibitors and taxine-based chemotherapy. More recently, we saw data from the TRITON3 trial exploring the role of rucaparib versus physicians' choice of docetaxel versus AR-inhibitor therapy in the mCRPC space for patients harboring BRCA 1, BRCA 2, or ATM mutation. Based on these data, it would be very tempting to offer a PARP inhibitor to the patient in case two. While regulatory authorities are still reviewing those data for approval, how would you consider treating this newly castrate-resistant patient in the frontline setting? Would you consider a PARP inhibitor in the frontline treatment of mCRPC in this patient with a BRCA 2 mutation? Dr. Jorge Garcia: So that's a loaded question, to be honest with you. We have compelling data, but controversial data, as you know as well. So I think that since we have a genomic profile on this patient and we know he had high volume disease, then the first thought to me is not a genetic or a genomic question or a sequence. It's actually a clinical question, to be honest with you. And that is: How are you progressing? Because I think that if you're progressing serologically, you and I may think of that patient differently. If you're progressing radiographically with alone plus minus PSA production but no symptoms, you may also tilt your scale into this life-prolonging agents in a different way. Whereas if you have true symptomatic disease, knowing what you know, prior therapy, CrPC with a BRCA 2 alteration, then you may actually go for something different. So if it's a rising PSA, if it is radiographic, but the patient is stable clinically, is not basically compromised by symptomatic disease, I do feel that a PARP inhibitor as a single agent would be a very reasonable choice. In this case, you can use, obviously, rucaparib. You can use olaparib. I don't have a vested interest in either/or. I think either/or is fine. The subtleties and side effects, as you know, the olaparib data was probably the data that you and I probably are more accustomed to, used to the most just by virtue of how the agents got registered in the United States. But either/or, I think a PARP inhibitor would be a reasonable approach. I think the question perhaps, and I pitch that back to you, is what are you looking for with a PARP inhibitor? Because, as you know, all DNA repair deficiencies are not biologically the same. They do not respond the same way to PARP inhibitors. And even BRCA 2, where we think it's monoallelic or biallelic, may have subtleties in how those patients respond to PARP therapy. But the answer is yes, obviously, you have a biomarker, the patient has it, you can use it. I think the question is, how are you going to follow the patient? And what is going to be the endpoint that you're going to pay attention to in this case to find that the patient has a benefit or not granted, that could be PSA driven, but I think that perhaps I'm pushing you to think beyond PSA. Dr. Kriti Mittal: I agree, Dr. Garcia. I think we need to think about the patient as a whole. PSA-based changes in treatment are not generally part of our practice. I think evaluating the patient for symptoms and also thinking about the sites of progression, sites of disease they've had in the past, preventing development of cord compression, because some of these patients progress very rapidly and present with cord compression at the time of progression. Those are the things we are trying to predict and prevent. I think in a patient with BRCA 2 mutation, in this situation, I would feel compelled to offer rucaparib, given that even in the intention-to-treat analysis, the hazard ratio was 0.6 in terms of median progression-free survival. I think what was quite impressive was the subset analysis comparing rucaparib versus docetaxel. And that was something surprising. And I think we'll have to wait for long-term outcomes. But certainly, for a BRACA 2-mutated patient, this could be a reasonable consideration provided the drug is available and approved. Dr. Jorge Garcia: As you know, the three most common DNA repair deficiencies that we see are BRCA1, BRCA2, and ATM. BRCA2 is probably the one that we see the most. But we also recognize that with the limited data we have for ATMs, that patients with an ATM abnormality do not tend to benefit the most. And then yet we have also another series of DNA repair deficiencies, deficiencies, PALB2, CHEK2, CDK12 and so forth. And yet we have some exquisite responses to some of those patients. So I can tell you that I have a patient of mine who had an ATM mutation, a germline ATM mutation, and I predicted that initially that the likelihood of benefit to a PARP inhibitor would be low. He was placed on a PARP inhibitor and surprise, surprise, he was on a PARP inhibitor for almost a couple of years. What I want to convey to the audience is that if you have the appropriate biomarker, you certainly should consider a PARP inhibitor in this scenario. I think the bigger question is also understanding that not every DNA repair would benefit the same way. So being very thoughtful and very structured as to how you're going to manage the patient, it cannot be PSA only, the patient has to be followed radiographically and clinically because I would argue that if this patient had just a serologic progression, I would put the patient on a PARP inhibitor and the PSA kinetics change north, but slowly, what is the urgency of you switching the patient to something else? And also the misconception that if you look at PROfound, that olaparib for that matter has to always be given after docetaxel. That's not the case. The makeup of PROfound is different than this patient, obviously, because this patient got triple therapy upfront, whereas most patients on the PROfound were CRPC who receive chemotherapy in the CRPC space. But yet undoubtedly, I think that your case illustrates the importance of next-generation sequencing and the importance of understanding the access to two oral PARP inhibitors that are super solid. I think that perhaps the bigger question is going to be should you do a PARP inhibitor alone or should we use a combination of a PARP inhibitor plus an oral agent, such as in this case, maybe abiraterone acetate plus olaparib. Or maybe even thinking of TALAPRO, maybe enza plus a PARP inhibitor. So I don't know where you sit on those thoughts, Doctor-. Dr. Kriti Mittal: I change toxicity considerations, temper my enthusiasm for offering PARP inhibitors in combination with AR inhibitors or abiraterone at this time. I think I would certainly consider monotherapy with rucaparib for a patient in this situation. I am not entirely convinced that putting a patient through dual treatment in the mCRPC setting in the frontline, I don't think we are there yet. Dr. Jorge Garcia: There are two very important trials that are looking at the combination of an adrenal biosynthesis inhibitor plus olaparib in this context, and one is PROpel and the other one is MAGNITUDE. And both trials have very different results in many ways because they look at patients with a biomarker, meaning DNA repair, and patients without the biomarker. And I think the bigger question is, should this patient who was an abiraterone– Let's say this patient hypothetically was on a PEACE-1-like style. So the patient got ADT or triple therapy but was an abiraterone or an adrenal biosynthesis inhibitor instead of chemotherapy. And the patient was progressing slowly on abiraterone, you knew that the patient had a DNA repair deficiency. How comfortable with the PROpel and MAGNITUDE data would you and I feel to add on or layer, if you allow me to express it like that, a PARP inhibitor into this regime? Dr. Kriti Mittal: My personal interpretation of the currently available data is that at this point, combination therapy is not something I would use in my clinical practice. I think there are two camps in the GU oncology community of how people interpret the PROpel, MAGNITUDE, TRITON, and TALAPRO data in full. I think each of these trials had very different patient populations. I think in a biomarker unselected population, I would certainly not advocate for combination therapy. But even in the biomarker-selected population, I think how the biomarkers were tested and how the populations were defined may not always match what we are doing in clinical practice. And so I would, at this time, advocate for monotherapy over combination therapy. Dr. Jorge Garcia: I'm sure the audience will have probably read or heard about PROpel and MAGNITUDE and the data in patients without a biomarker positivity disease. So I'd love to hear your thoughts as to if you had no biomarker. By that I mean if you had a patient with CRPC, with metastatic CRPC without a DNA repair deficiency, would you consider using an adrenal biosynthesis inhibitor and a PARP inhibitor together based upon the potential synergistic of additive benefits and some of the data to suggest that you can delay rPFS when you combine therapy, but in the absence of biomarker positivity. Dr. Kriti Mittal: In the absence of biomarker positivity, I think the preclinical data are stronger than the clinical results we are seeing in trials. So while I think we should continue researching further into this because there certainly is preclinical rationale, looking at the clinical outcomes from these several trials, I would not offer PARP inhibitor to an unselected patient. Dr. Jorge Garcia: Great. Dr. Kriti Mittal: Moving on to second-line treatment for castration-resistant prostate cancer. I think talking of access issues and talking about the current treatment paradigms in the United States, there is still not widespread availability of lutetium. The listeners would love to hear your thoughts, Dr. Garcia, on practical management tips, safety issues, and the multidisciplinary nature of the management of lutetium therapy. Dr. Kriti Mittal: So I think the challenges with lutetium are multiple. Number one is the correct identification of the patient, the ideal patient for lutetium. Secondly is who manages the patient and as you indicated, the importance of a team approach in that. Thirdly is how do we follow that patient during therapy? So it's beyond the technical aspects of who infuses the patient. Fourthly is what are the true goals of lutetium for that patient population and the side effects that those patients may embark on that some people may not be fully aware of and creates complexity. And lastly, perhaps, is how the movement, how we develop lutetium in CRPC and how we're going to move lutetium or have started to move lutetium and alike, meaning radiopharmaceuticals, radioligand-based therapies outside lutetium opinion and others as you know, earlier into the natural history of prostate cancer, maybe even in the locally advanced disease in combination with radiation or for patients with N1 positive disease. So it's a lot of movement in that space. I think that this is just the beginning of radiopharmaceutical entering diagnostics. But let me just address this succinctly, if I may. Number one, you do need a PET PSMA in order for you to select the patient because we're talking about a potential biomarker. But this is what I call an imaging biomarker. If you see it, you treat it. So the standard of care right now for lutetium is very simple: you need to have men with metastatic castration-resistant prostate cancer. Two, you need to have failed a prior oral agent, in this case, a novel hormonal agent, independent of which agent you have seen, independent of the timing when you have seen an oral agent at the front, the middle, the end. And lastly, you have to have progress through chemotherapy. Yet again, it depends on when you see chemo. So if you have someone who has high volume metastatic disease from the beginning, de novo disease, and you got ADT, daro, and docetaxel, and the patient progresses, that patient can go on. If that patient has a positive PSMA PET, that patient can go on to get lutetium. Similarly, if you have someone who got ADT alone in the adjuvant space for radiation therapy, progress, got an oral agent, progress, got a PARP or not, or got docetaxel, that patient could also be a candidate for lutetium. It's dependent on how you run the patient through therapy. Secondly is who gives lutetium? So I do believe, and I may be biased, I certainly believe in the importance of a team approach with radiation oncology and nuclear medicine. But the reality of it is, I believe these patients are so advanced in their stage of their disease, then the idea of quarterback, in my personal opinion, resides in medical oncology. And I think the bigger question is going to be if nuclear medicine at your given institution is going to be delivering lutetium, or is it going to be radiation oncology? And I think, as you know, in places in America, it's RadOnC, in other places is NucMed, in our institution right now it is NucMed. Having said that, I do predict that for those places where nuclear medicine is heavily involved in delivering lutetium or partnering with MedOnc to deliver lutetium, radiation oncology in the future will have a bigger role as well because we are moving lutetium earlier in settings where radiation oncology is commonly used, such as high-risk prostate cancer patients, or even in the salvage setting, or even in patients with metastatic disease, where we want to combine radiation and lutetium, which are part of clinical trials as we think through for the future. But either/or, I think the quarterback should be really MedOnc in this case. Thirdly is how do we do it? So clearly, at least in my practice, and I think it's probably standard across the United States, MedOnc will see the patient, determine viability and feasibility of therapy, determine who's the ideal candidate, discusses the pros and the cons, and then works along with RadOnc or NucMed to start the process. As you know, it is once every six weeks. So here in my practice, we will see the patient every time before treatment. Sometimes we see them the day off, sometimes we see them a few days before. Patients will get blood work. Specifically, we're interested in seeing everything CMPs, but certainly blood counts, red cell counts, platelets, and white cell counts, just to make sure that patients do not start with impaired bone marrow that can increase the risk for myelosuppression and therefore significant challenges with side effects, hematologic side effects, specifically. And we do that. Sometimes we see them, sometimes our nurse practitioners would do so. And then the patient will basically follow through and complete up to six cycles of treatments. Six times six, that's actually 36 weeks or so. That's a long time on therapy for those who can get six cycles. I think the question becomes how do you follow those patients? And if we pay attention to the VISION data, as you know, those patients were actually followed serially quite closely on trial every eight weeks for the first 24 weeks, and then they stretch the scans out. But the scans that we're using in the trial are conventional imaging. And I think the bigger question that you and I will have is if we get a PET PSMA to use to make that decision to get on lutetium PSMA, should I go back and use a CT or so to stage the patient? I think we're moving more toward PET follow-up, but we also don't know fully the impact of lutetium PSMA on PSMA metabolically during treatment. I think that we all recognize anecdotally and at least with some of the emerging data and we have the SUV may change, that PSA reductions also appear to be important as to define who is likely to benefit or not. But those are questions that remain to be seen, to be honest with you. We follow the patients serologically, clinically, and radiographically. And at least in my group, we tend to do PSMA PETs in between therapy to ascertain the impact of therapy in radiographic and also metabolic changes. And lastly is how we manage side effects. So I think that I'm pretty OCD about these patients because I have seen in my practice patients having outstanding responses to therapy but unfortunately become transfusion dependent, either transiently or permanently, just by virtue of side effects. And I think the importance of understanding the most common side effects of lutetium, in this case fatigue, myelosuppression, xerostomia, are really, really important. And that is the importance of having a multi-team effort approach so everybody is fully aware of the baseline characteristics of that patient or how the patient is enduring therapy and how the therapy is impacting the quality of life and impacting bone marrow production for those patients. I think I remind the audience that the vast majority of our patients do have bone metastases. In fact, in the VISION trial it was around what, over 85, 90% of patients are so with bone metastases. So their marrow has already been impacted not only by disease but equally importantly by the prior chemotherapy that they may have seen. And some of the patients that we have in the first bubble effect is they have seen probably docetaxel, some may even have seen dual therapy with cabazitaxel as a second-line chemotherapy. So I think the understanding as to how you manage the side effects is critically important for our patients as well. Dr. Kriti Mittal: Those are very relevant, practical life issues. Thank you Dr. Garcia for a terrific discussion on the application of recent advances in prostate cancer to clinical practice. [28:54] The ASCO Education podcast is where we explore topics ranging from implementing new cancer treatments and improving patient care to oncologists' well-being and professional development. If you have an idea for a topic or a guest you'd like to see on the ASCO Education Podcast, please email us at education@asco.org. To stay up to date with the latest episodes and explore other educational content, please visit education.asco.org. Dr. Jorge Garcia: Thank you, Kriti. It's great to see you and thanks again to ASCO for the amazing opportunity to be here with you guys today. I hope the audience can see the benefit of understanding how the many changes we have seen have impacted our patients in a positive way. So thank you again for the opportunity. Dr. Kriti Mittal: Thank you, Dr. Garcia, and thank you so much to the ASCO team for inviting me. This was a great experience. Thank you Dr. Garcia for sharing your perspective on incorporating recent research advances into the management of patients with de novo metastatic prostate cancer. The ASCO Education Podcast is where we explore topics ranging from implementing new cancer treatments and improving patient care to oncologists' well-being and professional development. If you have an idea for a topic or a guest you'd like to see on the ASCO Education Podcast, please email us at education@asco.org. To stay up to date with the latest episodes and explore other educational content, please visit education.asco.org. The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experiences, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.
Featuring perspectives from Dr Emmanuel S Antonarakis, Prof Karim Fizazi, Dr Rana R McKay, Dr Alicia K Morgans and Dr A Oliver Sartor, including the following topics: Current Management of Nonmetastatic Prostate Cancer Introduction (0:00) Case: A man in his early 70s diagnosed with localized prostate cancer who underwent a radical prostatectomy in 2010 experiences rising prostate-specific antigen (PSA) from 0.18 to 0.4; PSA doubling time 7 months; PSMA PET-negative for other sites of disease — David S Morris, MD (1:26) Case: A man in his early 70s with M0 hormone-sensitive prostate cancer (HSPC) with PSA persistence after radical prostatectomy received androgen deprivation therapy (ADT) intensification with abiraterone/prednisone and went to the ER with hypertension, palpitations, headache and abnormal liver function tests — Sandy Srinivas, MD (15:58) Faculty presentation: Dr Morgans (19:29) New Considerations in Treatment Intensification for Metastatic Hormone-Sensitive Prostate Cancer (mHSPC) Case: A man in his mid 60s with localized prostate cancer and biochemical recurrence 5 years after neoadjuvant and adjuvant leuprolide and intensity-modulated radiotherapy to the whole pelvis — Neeraj Agarwal, MD, FASCO (28:59) Case: A man in his early 80s who underwent radical prostatectomy 15 years ago and received radiotherapy and ADT for biochemical recurrences is now diagnosed with M0 castration-resistant prostate cancer with quickly rising PSA levels — Dr Morris (33:02) Faculty presentation: Prof Fizazi (41:54) Available and Emerging Strategies for Newly Diagnosed Metastatic Castration-Resistant Prostate Cancer (mCRPC) Discussion (53:41) Case: A man in his mid 60s diagnosed with metastatic HSPC and PSMA positivity in the pubic ramus, bilateral external iliac nodes and lungs — Dr Srinivas (57:03) Faculty presentation: Dr McKay (1:03:01) Identification and Management of mCRPC with a Homologous Recombination Repair (HRR) Gene Abnormality Case: A man in his early 50s with mCRPC after enzalutamide receives olaparib; somatic BRCA2 mutation; TP53 mutation on liquid biopsy — Dr Agarwal (1:18:21) Case: A man in his early 70s with high-grade localized prostate cancer treated with proton beam therapy and ADT for 2 years now has rising PSA and CT scan positive for retroperitoneal node; somatic BRCA2, TP53, FOXA1 and MEN1 mutations; microsatellite stable — Dr Morris (1:21:59) Faculty presentation: Dr Antonarakis (1:30:22) Management of Progressive mCRPC Case: A man in his late 70s with multiregimen-refractory mCRPC and a gBRCA2 mutation receives olaparib with a sustained response for several years — Dr Srinivas (1:43:10) Faculty presentation: Dr Sartor (1:48:35) CME information and select publications
Dr. Neeraj Agarwal and Dr. Jeanny Aragon-Ching discuss the CLEAR study in renal cell carcinoma, a new exploratory analysis combining the TheraP and VISION trials in metastatic urothelial cancer, and compelling advances in prostate cancer and across GU oncology in advance of the 2023 ASCO Annual Meeting. TRANSCRIPT Dr. Neeraj Agarwal: Hello and welcome to the ASCO Daily News Podcast. I'm Dr. Neeraj Agarwal, your guest host for the ASCO Daily News Podcast today. I'm the director of the Genitourinary Oncology Program and a professor of medicine at the University of Utah Huntsman Cancer Institute, and editor-in-chief of the ASCO Daily News. I'm delighted to welcome Dr. Jeanny Aragon-Ching, a GU medical oncologist and the clinical director of the Genitourinary Cancers Program at the Inova Schar Cancer Institute in Virginia. Today, we'll be discussing some key abstracts in GU oncology that will be featured at the 2023 ASCO Annual Meeting. Our full disclosures are available in the show notes and disclosures of all guests on the podcast can be found on our transcript at asco.orgDNpod. Jeanny, it's great to have you on the podcast today. Dr. Jeanny Aragon-Ching: Thank you so much, Dr. Agarwal, for having me. Dr. Neeraj Agarwal: Jeanny, let's begin with Abstract 4502 regarding long-term updated results on the CLEAR study. The abstract reports the final, prespecified overall survival analysis of the CLEAR trial, a four-year follow-up of lenvatinib plus pembrolizumab versus sunitinib in patients with advanced renal cell carcinoma. Dr. Jeanny Aragon-Ching: Yes, I would be happy to. So, just as a reminder, the combination of lenvatinib and pembrolizumab was initially approved by the FDA in August 2021 for first-line treatment of adult patients with advanced renal cell carcinoma. So, this was based on significant benefits that were seen in progression-free survival, which was a primary endpoint, but also showed improvement in the overall response rates compared with sunitinib in first-line advanced renal cell carcinoma. So this abstract reports on longer-term follow-up now at a median of 49.8 months, and PFS favored the combination lenvatinib and pembrolizumab compared to sunitinib across all MSKCC risk groups, and PFS benefit versus lenvatinib and pembro compared to sunitinib was maintained with a hazard ratio of 0.47. And even overall survival was also maintained with the combination with a hazard ratio of 0.79, and the overall survival favored the combination across all risk groups. If we look at the CR rate, it was 18.3% for the combination compared to 4.8% with sunitinib, unless patients in the combination arm received subsequent anticancer therapies, and that's intuitive. And the PFS2 was also longer with the combination at 43 months compared to 26 months. Now, it is important to note that grade III or more treatment-related adverse events did occur in about 74% of the patients in the combination of lenvatinib and pembro, compared to 60.3% in patients with sunitinib. Dr. Neeraj Agarwal: Jeanny, this is good news. So the main message from the abstract is that sustained results from this combination of lenvatinib plus pembrolizumab are being seen even after a longer follow-up of more than four years. Dr. Jeanny Aragon-Ching: Yes, I agree. So now, moving on, Neeraj, to a different setting in the RCC space, let's look at Abstract 4519, which is titled “Efficacy of First-line Immunotherapy-based Regimens in Patients with Sarcomatoid and/or Rhabdoid Metastatic Non-Clear Cell RCC: Results from the IMDC,” which will be discussed by Dr. Chris Labaki. So, Neeraj, based on this abstract, can you tell us a little bit more about the impact of these adverse pathologic risk features in non-clear cell RCC? Dr. Neeraj Agarwal: Of course. So, using real-world patient data, the IMDC investigators compared the outcomes of patients with metastatic non-clear cell RCC who were treated with immunotherapy-based combination regimens versus those who were treated with VEGF-TKIs alone. They also assessed the impact of sarcomatoid and rhabdoid features on response to IO-based combinations versus VEGF-TKIs. Of 103 patients with metastatic non-clear cell RCC who had rhabdoid or sarcomatoid features, 32% of patients were treated with immunotherapy-based combinations. After adjusting for confounding factors, the authors show that those treated with a combination of two immune checkpoint inhibitors or an immune checkpoint inhibitor with a VEGF-TKI combination had significantly improved overall survival, which was not reached in the immunotherapy combination group versus seven months within the VEGF-TKI group. Time to treatment failure and objective responses were also prolonged, significantly higher, and better in the immunotherapy groups compared with patients who were treated with VEGF-TKIs alone. Interestingly, if you look at those 430 patients with metastatic non-clear cell RCC who did not have sarcomatoid or rhabdoid features, they didn't seem to benefit with immunotherapy-based combinations. Dr. Jeanny Aragon-Ching: This is an exciting update, Neeraj. What are the key takeaways from this abstract? Dr. Neeraj Agarwal: So the main takeaway is if you see a patient with advanced non-clear cell RCC who has sarcomatoid and rhabdoid features, there appears to be a rather substantial and selective benefit with IO-based combinations. And in this context, I would like to highlight the ongoing SWOG 2200 trial also known as PAPMET2 trial, which is comparing the combination of cabozantinib plus atezolizumab. So immuno-therapy-based combinations versus cabozantinib alone in advanced papillary renal cell carcinoma setting. So this trial is being led by Dr. Benjamin Maughan and Dr. Monty Pal. And I like to encourage our listeners to consider referring their patients for involvement in this federally funded trial so that we can validate the data from this retrospective study in a prospective way. So, Jeanny, let's now move on to another important disease type which is urothelial carcinoma. There is a very recent accelerated FDA approval of the drug combination of enfortumab vedotin and pembrolizumab for cisplatin-ineligible metastatic urothelial carcinoma patients. This is Abstract 4505, which is being presented by Dr. Shilpa Gupta and colleagues. Can you please tell us more about this update? Dr. Jeanny Aragon-Ching: Yeah, absolutely. So, as you mentioned, Neeraj, the FDA just granted accelerated approval in April 2023 for this combination of enfortumab vedotin or EV, which is and ADC, antibody drug conjugate against nectin-4 and the PD-1 inhibitor pembroluzimab. So it's a combination for patients with locally advanced or metastatic urothelial carcinoma who are considered cisplatin ineligible. So this is nearly a four-year follow-up. So as a reminder, this was a phase 1b/2 trial that included 45 patients and it had a primary endpoint of safety and tolerability although the key secondary endpoints included confirmed overall responses, duration of response, progression-free survival, and the resist criteria was investigated via investigator and BICRs which is in a blinded independent central review. Even overall survival was a key secondary endpoint. So, the bottom line was the confirmed overall response by BICR was 73.3%, the disease control rate was about 84%, and the CR rate was 15.6% with a PFS of close to 13 months, and a 12-month overall survival rate of 83%. However, it is important to cite that there were treatment-related adverse events including skin reactions in 66%, neuropathy occurred in 62%, and ocular disorders in 40%. And there was a little bit of pneumonitis in close to 9%, colitis, and hypothyroidism, so there are side effects to watch out for. Dr. Neeraj Agarwal: So, Jeanny this is great. What is the key takeaway from this trial? Dr. Jeanny Aragon-Ching: So I think the most important thing is we now have a new combination of EV and pembro which shows very promising responses and survival in part which led to the FDA accelerated approval in the cisplatin-ineligible population of patients. However, we must note that the phase 3 trial of EV302 will ultimately establish which approach is really beneficial for all of our cisplatin-ineligible patients, either a carboplatin-based chemotherapy regimen or a non-platinum-based regimen such as EV and pembro. Dr. Neeraj Agarwal: Thanks Jeanny, would you like to discuss any other study in the bladder cancer space? Dr. Jeanny Aragon-Ching: Absolutely. I think Abstract 4508 from Dr. Seth Lerner and colleagues will be very relevant to our colleagues. This abstract is SWOG S1011, which is a phase 3 surgical trial to evaluate the benefit of a standard versus an extended lymphadenectomy performed at the time of radical cystectomy for muscle-invasive bladder cancer. Dr. Neeraj Agarwal: Yes. So this trial, as you said, is an important trial which randomized in a one-on-one fashion 618 patients with muscle-invasive bladder cancer undergoing radical cystectomy, and these patients were randomized to either standard lymph node dissection or an extended lymph node dissection. And standard lymph node dissection included, as we know, external and internal iliac and operative lymph node. The extended lymph node dissection included lymph nodes up to aortic bifurcation which included common iliac, presciatic, and presacral lymph nodes. At a median follow-up of approximately 6 years, there was no disease-free survival or overall survival benefit in patients undergoing an extended lymph node dissection compared to standard lymph node dissection. And extended lymph node dissection was also associated with greater morbidity and preoperative mortality. Dr. Jeanny Aragon-Ching: Very interesting data, Neeraj. So these results, I think, will be very useful for a lot of our surgical colleagues in both academia and the community who may still be inclined to perform extended lymphadenectomy during cystectomy. This study shows that it's actually not necessary. Dr. Neeraj Agarwal: Absolutely. So now let's move on to another disease type, which is very important - prostate cancer. There are several practice-informing abstracts that are worthwhile discussing. The first of these involves Abstract 5002, which looks at the impact of the PSA nadir as a prognostic factor after radiation therapy for localized prostate cancer, which will be presented by Dr. Praful Ravi and colleagues. Jeannie, can you please tell us more about this abstract? Dr. Jeanny Aragon-Ching: Yeah, definitely. So this abstract, as you mentioned, Neeraj, is a prognostic impact of PSA nadir of more than or equal to 0.1 nanogram per ml within six months after completion of radiotherapy for localized prostate cancer - an individual patient data analysis of randomized trials from the ICECaP Collaborative. Basically, it refers to an attempt to evaluate early surrogate measures to predict for long term outcomes such as prostate cancer-specific survival, metastases-free survival, and overall survival. So they looked at a big registry from the ICECaP collaboration that included 10,415 patients across 16 randomized controlled trials. And those men underwent treatment for intermediate risk and high risk prostate cancer treated with either radiation therapy alone in about a quarter of patients, or they got RT with short-term ADT in about 58% of patients, and 17% of them got RT with long-term ADT. So, after a median follow-up of ten years, what they found was, if you had a PSA nadir that is over or equal to 0.1 nanogram per ml within six months after completion of radiation therapy, it was associated with worse prostate cancer-specific survival, metastases-free survival, and overall survival. For instance, the five-year metastases-free survival for those who achieved a PSA nadir of less than 0.1 was 91% compared to those who did not, which was 79%. Therefore, they concluded that if you achieve a bad PSA of 0.1 or above within six months after you completed radiation, you had worse outcomes. Dr. Neeraj Agarwal: Jeanny, what is the key takeaway message from this study? Dr. Jeanny Aragon-Ching: The key takeaway from this ICECaP analysis is that this information would be very important to augment a signal-seeking endpoint, especially for clinical trial development, so that we can develop further strategies to de-escalate for those who don't need systemic intensification or therapy intensification versus escalation for those who really do. Dr. Neeraj Agarwal: So, my radiation oncology colleagues need to watch out for those patients who do not achieve a PSA of less than 0.1 nanogram per ml within the first six months of finishing radiation therapy. Very interesting data. Dr. Jeanny Aragon-Ching: Yes, absolutely. So. Neeraj another important abstract for our fellow clinicians, switching gears a little bit now, is Abstract 5011, which is titled “Do Bone Scans Overstage Disease Compared to PSMA PET?” This was an international, multicenter retrospective study with blinded, independent readers. Can you tell us more about this abstract? Dr. Neeraj Agarwal: Yes, a relatively small retrospective study, but still pertinent to our practice. So I'll summarize it. This study by Dr. Wolfgang Fendler and colleagues evaluated the ability of bone scans to detect osseous metastasis using PSMA PET scan as a reference standard. So in this multicenter retrospective study, 167 patients were included, of which 77 patients were at the initial staging of prostate cancer, 60 had biochemical recurrence after definitive therapy, and 30 patients had CRPC or castor-resistant disease. These patients had been imaged with a bone scan and a PSMA PET scan within 100 days. And in all patients, the positive predictive value, negative predictive value and specificity for bone scan were evaluated at different time points. They had bone scan and PSMA PET scan and both were compared. And what they found was interesting. All these three values - positive predictive value, negative predictive value, and specificity for bone scan were 0.73, 0.82 and 0.82 in all patients, and in initial staging, it was even lower at 0.43 and 0.94 and 0.80. So, without getting into too much detail regarding these numbers, I want to highlight the most important part of the study, that at the initial staging, 57% patients who had a positive bone scan had false positive bone scans. The interreader agreement for bone disease was actually moderate for bone scans and quite substantial for the PSMA PET scan. Dr. Jeanny Aragon-Ching: So, Neeraj, what do you think is the key takeaway message here for our audience? Dr. Neeraj Agarwal: The key takeaway message is that positive predictive value of bone scan was low in prostate cancer patients at initial staging, with the majority of positive bone scans being false positive. This suggests that a large proportion of patients which we consider to have low-volume metastatic disease by bone scan actually have localized disease. So in the newly diagnosed patients with prostate cancer, patients should ideally have a PSMA PET scan to rule out metastatic disease. So, let's move on to another abstract I would like to discuss, which has important implications in treatment, especially now that lutetium 177 is approved, but frankly not available widely. Dr. Jeanny Aragon-Ching: Yeah, that's actually very timely. So the abstract you're referring to is 5045, which is being presented by Dr. Yu Yang Sun and colleagues entitled “Effects of Lutetium PSMA 617 on Overall Survival in TheraP Versus VISION Randomized Trials: An Exploratory Analysis.” So, Neeraj, can you tell us more about the relevance of this exploratory analysis? Dr. Neeraj Agarwal: Definitely. In this abstract, Dr. Yang Sun and colleagues assess the effect of lutetium PSMA on overall survival in two different trials, TheraP and VISION trials. So, just for our listeners' recollection, the phase 2 TheraP trial compared lutetium PSMA and cabazitaxel in patients with mCRPC who had progression on docetaxel and had significant PSMA avidity on gallium PSMA pet scan, which was defined as a minimum uptake of SUV max of 20 at least one site of disease and SUV max of more than 10 at all sites of measurable disease. In this trial, 20 of 101 patients in the cabazitaxel arm crossed over to lutetium PSMA, and 32 of 99 patients in the lutetium PSMA arm crossed over to cabazitaxel. In the VISION trial, patients with mCRPC who previously progressed on at least one ARPI and one taxane-based therapy and had a positive gallium PSMA scan, and here, positivity was not stringently pre-specified as it was done in the context of TheraP trial. So, positive gallium pet scans were randomly assigned in two to one fashion to receive either lutetium PSMA plus best supportive care or standard of care versus standard of care. And I'd like to highlight that the standard of care comprised ARPIs and bone protecting agents and these patients were not allowed to have cytotoxic chemotherapy such as cabazitaxel in the standard of care arm. Now, overall survival was similar in the lutetium PSMA group regardless of whether they got lutetium PSMA in the VISION trial or TheraP trial. There was no difference in overall survival with lutetium in the lutetium arms of VISION and TheraP trial with a hazard ratio of 0.92. And there was no difference in the overall survival between the lutetium PSMA and the cabazitaxel group in the TheraP trial if you use counterfactual analysis, assuming crossover had not occurred. So, quite interesting in my view. Dr. Jeanny Aragon-Ching: Yeah, thanks Neeraj for that wonderful synopsis and discussion. So, what is the key take home message then? Dr. Neeraj Agarwal: The main message in this new exploratory analysis, which combined both the TheraP and VISION trials, is that lutetium PSMA and cabazitaxel seem to be associated with similar overall survival benefit in these highly selected patients with PSMA positivity. Additionally, the difference in the observed effect of lutetium PSMA and overall survival in the TheraP and VISION trials may be actually better explained by the use of different treatments in the respective control arms of these trials. And these results, in my view, are quite pertinent for those patients and providers who do not have access to lutetium-177 therapy. Let's go to another abstract that is currently relevant to our practice, given many patients with advanced prostate cancer who have concurrent diabetes; I'm talking about Abstract 5066. Jeanny, can you please tell us more about this abstract? Dr. Jeanny Aragon-Ching: Certainly, Neeraj. So this abstract will be presented by Dr. Amy Shaver and colleagues. So it's also very relevant, since many men who are diagnosed with prostate cancer frequently also have a concomitant diagnosis of type 2 diabetes mellitus. So, this was a SEER-Medicare population database analysis that looked at men who were treated with either abiraterone or enzalutamide and also had concomitant diagnosis of type 2 diabetes mellitus (DM). And they were identified using ICD-9 and ICD-10 codes and they were all tied in to acute care utilization. So they looked at CMS research data codes and ER hospitalization visits six months after treatment initiation was recorded. So all in all, they took a sample of 11,163 men, of whom close to 62% were treated with abiraterone and about 38% were treated with enzalutamide. So, of these, about 27% of them had type 2 DM, of whom 59% received abiraterone and about 41% had enzalutamide. So, the bottom line is, compared to those without diabetes mellitus, those who had type 2 diabetes had worse acute care utilization, which was 43% higher than those who got abiraterone compared to enzalutamide, and also had higher overall mortality. Therefore, the bottom line is, having type 2 diabetes mellitus, unfortunately, portends worse outcomes in men with prostate cancer, so careful attention needs to be paid to those who are starting out already with such comorbidities. So Neeraj, any final thoughts you have regarding this abstract and overall before we wrap up on the podcast today? Dr. Neeraj Agarwal: Absolutely. So it looks like, based on this very important pertinent Abstract 5066, which talks about the impact of diabetes on our patients, I think we need to be very watchful regarding the impact of diabetes on our patients who are being treated with abiraterone or enzalutamide, especially drugs which are known to make the metabolic syndrome and diabetes worse. I think close monitoring and close attention to control of diabetes is very important. So with that, I would urge the listeners to come and join us at the Annual Meeting, not only to celebrate these successes but also to help disseminate this cutting-edge data to practitioners and maximize the benefit to our patients across the globe. And thank you to our listeners for joining us today. You will find links to the abstracts we discussed today on the transcript of this episode. Finally, if you value the insights that you hear on our ASCO Daily News Podcast, please take a moment to rate, review and subscribe wherever you get your podcast. Disclaimer: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Find out more about today's speakers: Dr. Neeraj Agarwal @neerajaiims Dr. Jeanny Aragon-Ching Follow ASCO on social media: @ASCO on Twitter ASCO on Facebook ASCO on LinkedIn Disclosures: Dr. Neeraj Agarwal: Consulting or Advisory Role: Pfizer, Bristol-Myers Squibb, AstraZeneca, Nektar, Lilly, Bayer, Pharmacyclics, Foundation Medicine, Astellas Pharma, Lilly, Exelixis, AstraZeneca, Pfizer, Merck, Novartis, Eisai, Seattle Genetics, EMD Serono, Janssen Oncology, AVEO, Calithera Biosciences, MEI Pharma, Genentech, Astellas Pharma, Foundation Medicine, and Gilead Sciences Research Funding (Institution): Bayer, Bristol-Myers Squibb, Takeda, Pfizer, Exelixis, Amgen, AstraZeneca, Calithera Biosciences, Celldex, Eisai, Genentech, Immunomedics, Janssen, Merck, Lilly, Nektar, ORIC Pharmaceuticals, Crispr Therapeutics, Arvinas Dr. Jeanny Aragon-Ching: Honoraria: Bristol-Myers Squibb, EMD Serono, Astellas Scientific and Medical Affairs Inc., Pfizer/EMD Serono Consulting or Advisory Role: Algeta/Bayer, Dendreon, AstraZeneca, Janssen Biotech, Sanofi, EMD Serono, MedImmune, Bayer, Merck, Seattle Genetics, Pfizer, Immunomedics, Amgen, AVEO, Pfizer/Myovant, Exelixis, Speakers' Bureau: Astellas Pharma, Janssen-Ortho, Bristol-Myers Squibb, Astellas/Seattle Genetics.
In this episode of ASCO Educational podcasts, we'll explore how we interpret and integrate recently reported clinical research into practice. The first scenario involves a 72-year old man with high-risk, localized prostate cancer progressing to hormone-sensitive metastatic disease. Our guests are Dr. Kriti Mittal (UMass Chan Medical School) and Dr. Jorge Garcia (Case Western Reserve University School of Medicine). Together they present the patient scenario (1:12), review research evidence regarding systemic and radiation therapy for high-risk localized disease (5:45), and reflect on the importance of genetic testing and (10:57) and considerations for treatment approaches at progression to metastatic disease (16:13). Speaker Disclosures Dr. Kriti Mittal: Honoraria – IntrinsiQ; Targeted Oncology; Medpage; Aptitude Health; Cardinal Health Consulting or Advisory Role – Bayer; Aveo; Dendreon; Myovant; Fletcher; Curio Science; AVEO; Janssen; Dedham Group Research Funding - Pfizer Dr. Jorge Garcia: Honoraria - MJH Associates: Aptitude Health; Janssen Consulting or Advisor – Eisai; Targeted Oncology Research Funding – Merck; Pfizer; Orion Pharma GmbH; Janssen Oncology; Genentech/Roche; Lilly Other Relationship - FDA Resources ASCO Article: Implementation of Germline Testing for Prostate Cancer: Philadelphia Prostate Cancer Consensus Conference 2019 ASCO Course: How Do I Integrate Metastasis-directed Therapy in Patients with Oligometastatic Prostate Cancer? (Free to Full and Allied ASCO Members) If you liked this episode, please follow the show. To explore other educational content, including courses, visit education.asco.org. Contact us at education@asco.org. TRANSCRIPT Dr. Kriti Mittal: Hello and welcome to this episode of the ASCO Education Podcast. Today we'll explore how we interpret and integrate recently reported clinical research into practice, focusing on two clinical scenarios: localized prostate cancer progressing to hormone-sensitive metastatic disease; and a case of de novo metastatic hormone-sensitive prostate cancer progressing to castration-resistant disease. My name is Kriti Mittal and I am the Medical Director of GU Oncology at the University of Massachusetts. I am delighted to co-host today's discussion with my colleague, Dr. Jorge Garcia. Dr. Garcia is a Professor of Medicine and Urology at Case Western Reserve University School of Medicine. He is also the George and Edith Richmond Distinguished Scientist chair and the current chair of the Solid Tumor Oncology Division at University Hospital's Seidman Cancer Center. Let me begin by presenting the first patient scenario. Case 1: A 72-year-old male was referred to urology for evaluation of hematuria. A rectal exam revealed an enlarged prostate without any nodules. A CT urogram was performed that revealed an enlarged prostate with bladder trabeculations. A cystoscopy revealed no stones or tumors in the bladder, but the prostatic urethra appeared to be abnormal looking. Transurethral resection of the prostate was performed. The pathology revealed Gleason score 4+5=9 prostate cancer, involving 90% of the submitted tissue. PSA was performed one week later and was elevated at 50. Patient declined the option of radical prostatectomy and was referred to radiation and medical oncology. So I guess the question at this point is, Dr. Garcia, in 2023, how do you stage patients with high-risk localized prostate cancer and how would you approach this case? Dr. Jorge Garcia: That's a great question and a great case, by the way, sort of what you and I in our practice will call ‘bread and butter'. Patients like this type of case that you just presented come from different places to our practice. So either they come through urology or oftentimes they may come through radiation oncology. And certainly, it depends where you practice in the United States, at ‘X', US, they may come through medical oncology. So I think that the first question that I have is in whatever role I'm playing in this case, where the patient has seen a urologist or a rad onc or me first, I think it's important for us in medical oncology, at least in the prostate cancer space, to talk about how do we think of their case and put those comments into context for the patient. It's very simple for you to tell a patient you can probably have surgery, radiation therapy, but at the end of the day, how do you counsel that patient as to the implications of the features of his disease is going to be really important. I use very simple examples that I relate to my patients, but really this patient is a patient that has very high-risk prostate cancer based upon the NCCN guidelines and how we actually stratify patients into what we call low-risk, intermediate-, and high-risk, and between those very low and very high risk. So his PSA is high, very high, I would argue. His Gleason score, now, what we call group grading is high. He has high-volume disease. So the first question that I would have is, what are the choices for treatment for a patient like this? But even before you and I may talk about treatment options, we really want to understand the volume of their disease and whether or not they have localized prostate cancer with high-risk features or whether or not they have locally advanced or hopefully not metastatic disease. So back in the days prior to the FDA approval for PSMA PET imaging, we probably will have a Technetium-99 whole-body bone scan, and/or we probably will actually use CT scanning. Most people in the past, we used to do just a CT of the abdomen and pelvic region. As you know, with the movement of oral agents in the advanced setting, I think most of us will do a chest CT, abdomen and pelvic region, and certainly we also probably will have a Technetium-99 bone scan. Now, with the utility and the use of PET imaging, I think most people like him will probably undergo PET PSMA, where you use F-18 PSMA or Gallium-68 PSMA. I think the importance depends on how you look at the approval of these two technologies. I think that PET PSMA imaging is here to stay. It's probably what most of us will use. And based upon that, we will define yet the truest stage of this patient. So right now, what we know is he has high-risk features. Hopefully, their disease is localized. We'll probably put the patient through an imaging technology. If you don't have access to a PET, then obviously CT and a bone scan will do. But if you do, the PET will actually help us define if the patient has disease outside of the prostate region, in the pelvic area, or even if they have distant metastases. Dr. Kriti Mittal: I would agree with that approach, Dr. Garcia. I think in the United States, we've been late adopters of PSMA scans. I think this patient with high-risk localized disease, if insurance allows at our institution, would get a PSMA for staging. There are still some patients where insurance companies, despite peer-to-peer evaluations, are not approving PSMAs. And in those situations, the patient would benefit from conventional CTs and a bone scan. So let's say this patient had a PSMA and was found not to have any regional or distant metastases. He decided against surgery, and he is seeing you as his medical oncologist together with radiation. What would your recommendations be? Dr. Jorge Garcia: I think the bigger question is, do we have any data to suggest or to demonstrate that if in the absence of metastatic disease with conventional imaging or with emerging technologies such as PSMA PET, there is no evidence of distant disease, which I think you probably agree with me, that would be sort of unlikely with a patient with these features not to have some form of PSMA uptake somewhere in their body. But let's assume that indeed then the PSMA PET was negative, so we're really talking about high-risk localized prostate cancer. So I don't think we can tell a patient that radical prostatectomy would not be a standard of care. We never had a randomized trial comparing surgery against radiation therapy. This patient has already made that decision and surgery is not an option for him. If he, indeed, had elected radiotherapy, the three bigger questions that I ask myself are where are you going to aim the beam of that radiation therapy? What technology, dose, and fractionation are you going to use? And lastly, what sort of systemic therapy do you need, if any, for that matter? Where we do have some data maybe less controversial today in 2023 compared to the past? But I think the question is, do we do radiation to the prostate only or do we expand the field of that radiation to include the pelvic nodes? Secondly, do we use IMRT? Do you use proton beam or not? Again, that's a big question that I think that opens up significant discussions. But more important, in my opinion, is the term of hypofractionation. I think the field of radiation oncology has shifted away from the old standard, five, seven weeks of radiation therapy to more hypofractionation, which in simple terms means a higher dose over a short period of time. And there was a concern in the past that when you give more radiation on a short period of time, toxicities or side effects would increase. And I think that there is plenty of data right now, very elegant data, demonstrated that hypofractionation is not worse with regards to side effects. I think most of us will be doing or supporting hypofractionation. And perhaps even to stretch that, the question now is of SBRT. Can we offer SBRT to a selected group of patients with high-risk prostate cancer? And again, those are discussions that we will naturally, I assume, in your practice, in your group, you probably also have along with radiation oncology. Now, the bigger question, which in my mind is really not debatable today in the United States, is the need for systemic therapy. And I think we all will go back to the old data from the European EORTC data looking at the duration of androgen deprivation therapy. And I think most of us would suggest that at the very least, 24 months of androgen deprivation therapy is the standard of care for men with high-risk prostate cancer who elect to have local definitive radiation therapy as their modality of treatment. I think that whether or not it's 24 or 36, I think that the Canadian data looking at 18 months didn't hit the mark. But I think the radiation oncology community in the prostate cancer space probably has agreed that 24 months clinically is the right sort of the sweetest spot. What I think is a bit different right now is whether or not these patients need treatment intensification. And we have now very elegant data from the British group and also from the French group, suggesting, in fact, that patients with very high-risk prostate cancer who don't have evidence of objective metastasis may, in fact, benefit from ADT plus one of the novel hormonal agents, in this case, the use of an adrenal biosynthesis inhibitor such as abiraterone acetate. So I think in my practice, what I would counsel this patient is to probably embark on radiotherapy as local definitive therapy and also to consider 24 months of androgen deprivation therapy. But I would, based upon his Gleason score of group grading, his high-volume disease in the prostate gland, and his PSA, to probably consider the use of the addition of abiraterone in that context. Dr. Kriti Mittal: That is in fact how this patient was offered treatment. The patient decided to proceed with radiation therapy with two years of androgen deprivation. And based on data from the multi-arm STAMPEDE platform, the patient met two of the following three high-risk features Gleason score >8, PSA >40, and clinical >T3 disease. He was offered two years of abiraterone therapy. Unfortunately, the patient chose to decline upfront intensification of therapy. In addition, given the diagnosis of high-risk localized prostate cancer, the patient was also referred to genetic counseling based on the current Philadelphia Consensus Conference guidelines. Germline testing should be considered in patients with high-risk localized node-positive or metastatic prostate cancer, regardless of their family history. In addition, patients with intermediate-risk prostate cancer who have cribriform histology should also consider germline genetic testing. Access to genetic counseling remains a challenge at several sites across the US, including ours. There is a growing need to educate urologists and medical oncologists to make them feel comfortable administering pretest counseling themselves and potentially ordering the test while waiting for the results and then referring patients who are found to have abnormalities for a formal genetics evaluation. In fact, the Philadelphia Consensus Conference Guideline offers a very elegant framework to help implement this workflow paradigm in clinical practice. And at our site, one of our fellows is actually using this as a research project so that patients don't have to wait months to be seen by genetics. This will have implications, as we will see later in this podcast, not only for this individual patient as we talk about the role of PARP inhibitors but also has implications for cascade testing and preventative cancer screening in the next of kin. Dr. Jorge Garcia: Dr. Mittal, I think that we cannot stress enough the importance of genetic testing for these patients. Oftentimes I think one of the challenges that our patients are facing is how they come into the system. If you come through urology, especially in the community side, what I have heard is that there are challenges trying to get to that genetic counsel. Not so much because you cannot do the test, but rather the interpretation of the testing and the downstream effect as you're describing the consequences of having a positive test and how you're going to counsel that patient. If you disregard the potential of you having an active agent based upon your genomic alteration, is the downstream of how your family may be impacted by a finding such as the DNA repair deficiency or something of that nature. So for us at major academic institutions because the flow how those patients come through us, and certainly the bigger utilization of multi-disciplinary clinics where we actually have more proximity with radiation oncology urology, and we actually maybe finesse those cases through the three teams more often than not, at least discuss them, then I think that's less likely to occur. But I think the bigger question is the timing of when we do testing and how we do it. So there are two ways -- and I'd love to hear how you do it at your institution -- because there are two ways that I can think one can do that. The low-hanging fruit is you have tissue material from the biopsy specimen. So what you do, you actually use any of the commercial platforms to do genomic or next-generation sequencing or you can do in-house sequencing if your facility has an in-house lab that can do testing. And that only gets you to what we call ‘somatic testing', which is really epigenetic changes over time that are only found in abnormal cells. It may not tell you the entire story of that patient because you may be missing the potential of identifying a germline finding. So when you do that, did you do germline testing at the same time that you do somatic testing or did you start with one and then you send to genetic counseling and then they define who gets germline testing? Dr. Kriti Mittal: So at our site, we start with germline genetic testing. We use either blood testing or a cheek swab assay and we send the full 84-gene multigene panel. Dr. Jorge Garcia: Yeah, and I think for our audience, Dr. Mittal, that's great. I don't think you and I will be too draconian deciding which platform one uses. It's just that we want to make sure that at least you test those patients. And I think the importance of this is if you look at the New England Journal paper from many years ago, from the Pritchard data looking at the incidence of DNA repair deficiency in men with prostate cancer in North America, that was about what, around 10% or so, take it or leave it. So if you were to look only for germline testing, you only will, in theory, capture around 10% of patients. But if you add somatic changes that are also impacting the DNA pathway, then you may add around 23%, 25% of patients. So we really are talking that if we only do one type of testing, we may be missing a significant proportion of patients who still may be candidates, maybe not for family counseling if you had a somatic change, rather than germline testing, the positivity, but if you do have somatic, then you can add into that equation the potential for that patient to embark on PARP inhibitors down the road as you stated earlier. It may not change how we think of the patient today, or the treatment for that matter. But you may allow to counsel that patient differently and may allow to sequence your treatments in a different way based upon the findings that you have. So I could not stress the importance of the NCCN guidelines and the importance of doing genetic testing for pretty much the vast majority of our patients with prostate cancer. Dr. Kriti Mittal: Going back to our patient, three years after completion of his therapy, the patient was noted to have a rising PSA. On surveillance testing, his PSA rose from 0.05 a few months prior to 12.2 at the time of his medical oncology appointment. He was also noted to have worsening low back pain. A PSMA scan was performed that was noteworthy for innumerable intensely PSMA avid osseous lesions throughout his axial and appendicular skeleton. The largest lesion involved the right acetabulum and the right ischium. Multiple additional sizable lesions were seen throughout the pelvis and spine without any evidence of pathologic fractures. So the question is, what do we do next? Dr. Jorge Garcia: The first question that I would have is, the patient completed ADT, right? So the patient did not have treatment intensification, but at the very least he got at least systemic therapy based upon the EORTC data. And therefore, one would predict that his outcome will have been improved compared to those patients who receive either no ADT or less time on ADT. But what I'm interested in understanding is his nadir PSA matters to me while he was on radiation and ADT. I would like to know if his nadir PSA was undetectable, that's one thing. If he was unable to achieve an undetectable PSA nadir, that would be a different thought process for me. And secondly, before I can comment, I would like to know if you have access to his testosterone level. Because notably, what happens to patients like this maybe is that you will drive down testosterone while you get ADT, PSAs become undetectable. Any of us could assume that the undetectability is the result of the radiation therapy. But the true benefit of the combination of radiation and ADT in that context really comes to be seen when the patient has got off the ADT, has recovered testosterone, and only when your testosterone has normalized or is not castrated, then we'll know what happens with your serologic changes. If you rise your PSA while you recover testosterone, that is one makeup of patient. But if you rise your PSA while you have a testosterone at the castrated level, that would be a different makeup of a patient. So do we have a sense as to when the patient recovered testosterone and whether or not if his PSA rose after recovery? Dr. Kriti Mittal: At the time his PSA rose to 12, his testosterone was 275. Dr. Jorge Garcia: Okay, perfect. You and I would call this patient castration-naive or castration-sensitive. I know that it's semantics. A lot of people struggle with the castration-naive and castration-sensitive state. What that means really to me, castration-naive is not necessarily that you have not seen ADT before. It's just that your cancer progression is dependent on the primary fuel that is feeding prostate cancer, in this case, testosterone or dihydrotestosterone, which is the active metabolite of testosterone. So in this case, recognizing the patient had a testosterone recovery and his biochemical recurrence, which is the rising of his PSA occur when you have recovery of testosterone, makes this patient castration-sensitive. Now the PET scan demonstrates now progression of his disease. So clearly he has a serologic progression, he has radiographic progression. I assume that the patient may have no symptoms, right, from his disease? Dr. Kriti Mittal: This patient had some low back pain at the time of this visit. So I think we can conclude he has clinical progression as well. Dr. Jorge Garcia: Okay, so he had the triple progression, serologic, clinical, and radiographic progression. The first order of business for me would be to understand the volume of his disease and whether we use the US CHAARTED definition of high volume or low volume, or whether we use the French definition for high volume from Latitude, or whether we use STAMPEDE variation for definition, it does appear to me that this patient does have high-volume disease. Why? If you follow the French, it's a Gleason score of >8, more than three bone metastases, and the presence of visceral disease, and you need to have two out of the three. If you follow CHAARTED definition, we did not use Gleason scoring, the US definition. We only use either the presence of visceral metastases or the presence of more than four bone lesions, two of which had to be outside the appendicular skeleton. So if we were to follow either/or, this patient would be high-volume in nature. So the standard of care for someone with metastatic disease, regardless of volume, is treatment intensification, is you suppress testosterone with androgen deprivation therapy. And in this case, I'd love to hear how you do it in Massachusetts, but here, for the most part, I would actually use a GnRH agonist-based approach, any of the agents that we have. Having said that, I think there is a role to do GnRH antagonist-based therapy. In this case, degarelix, or the oral GnRH antagonist, relugolix, is easier to get patients on a three-month injection or six-month injection with GnRH agonist than what it is on a monthly basis. But I think it's also fair for our audience to realize that there is data suggesting that perhaps degarelix can render testosterone at a lower level, meaning that you can castrate even further or have very low levels of testosterone contrary to GnRH agonist-based approaches. And also for patients maybe like this patient that you're describing, you can minimize the flare that possibly you could get with a GnRH agonist by transiently raising the DHT before the hypothalamic-pituitary axis would shut it down. So either/or would be fine with me. Relugolix, as you know, the attraction of relugolix for us right now, based upon the HERO data, is that you may have possibly less cardiovascular side effects. My rationale not to use a lot of relugolix when I need treatment intensification is quite simple. I'm not aware, I don't know if you can mitigate or minimize that potential cardiovascular benefit by adding abiraterone or adding one of the ARIs, because ARIs and abiraterone by themselves also have cardiovascular side effects. But either/or would be fine with me. The goal of the game is to suppress your male hormone. But very important is that regardless of volume, high or low, every patient with metastatic disease requires treatment intensification. You can do an adrenal biosynthesis inhibitor such as abiraterone acetate. You can pick an androgen receptor inhibitor such as apalutamide or enzalutamide if that's the case. The subtleties in how people feel comfortable using these agents, I think, none of us – as you know, Dr. Mittal - can comment that one oral agent is better than the other one. Independently, each of these three oral agents have randomized level 1, phase III data demonstrating survival improvement when you do treatment intensification with each respective agent. But we don't have, obviously, head-to-head data looking at this. What I think is different right now, as you know, is the data with the ARASENS data, which was a randomized phase III trial, an international effort looking at triple therapy, and that is male hormone suppression plus docetaxel-based chemotherapy against testosterone suppression plus docetaxel-based chemotherapy plus the novel androgen receptor inhibitor known as darolutamide. This trial demonstrated an outcome survival improvement when you do triple therapy for those high-volume patients. And therefore, what I can tell you in my personal opinion and when I define a patient of mine who is in need of chemotherapy, then the standard of care in my practice will be triple therapy. So if I know you are a candidate for chemotherapy, however, I make that decision that I want you to get on docetaxel upfront. If you have high-volume features, then the standard of care would not be ADT and chemo alone, it would be ADT, chemo, and darolutamide. What I don't know, and what we don't know, as you know, is whether or not triple therapy for a high-volume patient is better, the same, equivalent, or less than giving someone ADT plus a novel hormonal agent. That is the data that we don't have. There are some meta-analyses looking at the data, but I can tell you that at the very least, if you prefer chemo, it should be triple therapy. If you prefer an oral agent, it certainly should be either apalutamide, abiraterone acetate, and/or enzalutamide. But either/or, patients do need treatment intensification, and what is perplexing to me, and I know for you as well, is that a significant proportion of our patients in North America are still not getting treatment intensification, which is really sub-optimal and sub-standard for our practice. Dr. Kriti Mittal: Thank you, Dr. Garcia, for a terrific discussion on the application of recent advances in prostate cancer to clinical practice. In an upcoming podcast, we will continue that discussion exploring management of de novo metastatic prostate cancer. The ASCO Education Podcast is where we explore topics ranging from implementing new cancer treatments and improving patient care to oncologists' well-being and professional development. If you have an idea for a topic or a guest you'd like to see on the ASCO Education Podcast, please email us at education@asco.org. To stay up to date with the latest episodes and explore other educational content, please visit education.asco.org. The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.
Guest host Dr. Neeraj Agarwal and Dr. Christian Kollmannsberger discuss practice-changing abstracts that were presented at the 2023 ASCO Genitourinary Cancers Symposium, including results from the TALAPRO-2, PROpel, TRITON3, ARASENS, KEYNOTE-057, CheckMate 274, and CheckMate 9ER studies. TRANSCRIPT Dr. Neeraj Agarwal: Hello and welcome to the ASCO Daily News Podcast. I'm Dr. Neeraj Agarwal, the director of the Genitourinary Oncology Program, and professor of Medicine at the Huntsman Cancer Institute at the University of Utah, and editor-in-chief of the ASCO Daily News. Today, we will be discussing practice-changing abstracts and other key advances in GU Oncology featured at the 2023 ASCO Genitourinary Cancers Symposium. Joining me for this discussion is Dr. Christian Kollmannsberger, the chair of this year's ASCO GU. Dr. Kollmannsberger is a GU medical oncologist at the BC Cancer Vancouver Cancer Center and a clinical professor at the University of British Columbia. Our full disclosures are available in the transcript of this episode, and the disclosures of all guests on the podcast can be found on our transcripts at asco.org/DNpod. Christian, thank you for joining us on the podcast today. Dr. Christian Kollmannsberger: Thank you very much, Neeraj. It's a real pleasure to be here and have this discussion. Dr. Neeraj Agarwal: Thank you. So, Christian, the GU meeting featured remarkable progress in various GU malignancies. Could you please share some of the prominent topics that made the headlines this year and give us an overall feel of ASCO GU this year? Dr. Christian Kollmannsberger: Absolutely. I think it was a great meeting with over 5,800 attendees from more than 70 countries. And most of the attendees were in person, so it was a great event. ASCO GU is truly the premier global event to feature the very best of GU cancer research and treatment. The theme of this year's meeting was "Today's Science, Tomorrow's Treatment," and that was reflected in the novel scientific and clinical findings that were presented and will potentially lead to changes in our daily clinical practice. It also reminds us how quickly the development today is and how quickly novel scientific progress is immediately translated into clinical practice, particularly oncology. I was very impressed by the meeting's emphasis on diversity, interactivity, networking, multidisciplinary collaboration, and evidence-based care. We introduced several new features such as a “Meet the Professor session, a women's networking event, etc. And the first day really kicked off with a very rich focus on prostate cancer and much attention given to PARP inhibitors in our first session. As an example, LBA 17 was the first late-breaking abstract presented. And congratulations to you, Neeraj, on delivering this exciting data on the TALAPRO-2 trial, which were eagerly awaited. Let's start with that. Can you tell us about this trial? Dr. Neeraj Agarwal: Yes, of course. So the TALAPRO-2 trial was a phase 3 randomized trial where patients in newly diagnosed metastatic CRPC settings were randomized to standard of care enzalutamide plus placebo versus enzalutamide plus talazoparib PARP inhibitor. And as we know, Christian, the rationale has been that dual inhibition of PARP and AR may enhance the efficacy of each. And there's a laboratory preclinical rationale and based on which other studies have been done in the past. So, without getting into too much detail into the rationale for the trial, I'll come right to the results of the trial. So, this was the first-line mCRPC setting where rPFS was the primary endpoint as assessed by the independent radiology assessment. And in this trial, patients were recruited regardless of the homologous recombination repair gene alterations. So, patients were recruited and they were prospectively tested for whether they had these HRR gene alterations or not, but all comer population was included in this trial. And after a median follow-up of approximately 23 months, the trial read out, and we found that trial made the primary endpoint was improved radiographic progression-free survival with the rPFS being about 22 months in the enzalutamide arm and not reached in the combination arm with a 37% reduction in risk of progression or death. If you look at the subgroup analysis of patients who were HRR+, there was a 54% reduction risk of progression or death. If you look at patients who were stratified in HRR- or unknown group, there was a 30% reduction risk of progression or death. If you specifically look at an exploratory analysis we did to look for patients who were HRR- by prospective tumor tissue testing; there was a 34% reduction in risk of death with a hazard ratio of 0.66 favoring the combination arm. So overall, the rPFS primary endpoint was met in all groups. We also see significant delay in PSA progression in the combination arm by more than nine months. We also see delays in the time to cytotoxic chemotherapy. We saw delay in progression or death on subsequent neoplastic therapy after the protocol treatment. We saw delays in deterioration of quality of life and global health status. All these were significant and happened on the talazoparib plus enzalutamide arm. So overall, if you look at the totality of the data, these all favored the combination of talazoparib plus enzalutamide compared to enzalutamide alone. I want to highlight that overall survival is immature at 31% maturity with a hazard issue of 0.89, currently favoring enzalutamide plus talazoparib. But we'll have to look at more mature data as time passes. Dr. Christian Kollmannsberger: Wow. Thank you, Neeraj. So, it sounds like that was a very positive trial, and it's potentially practice-changing. One of the concerns is always safety and toxicity. So can you tell us whether there were any new safety signals, and can you tell us more about the common adverse events that were noticed in TALAPRO-2? Dr. Neeraj Agarwal: No discussion is complete without talking about safety results, so I'm glad you asked me, Christian. The most common dose-affecting toxicity, if you will - so toxicities which led to dose modification and dose discontinuation of talazoparib were cytopenias, as we expect from this class of agents. So anemia, neutropenia, thrombocytopenia, these were the common toxicities. In fact, rate with anemia was 46.5%. Neutropenia and cytopenia were much less common. I would like to highlight one fact which also came up during the discussion section after our oral presentation. The qualifying criteria for entry in this trial was a hemoglobin of 9-gram percent. And 49% of patients had grade 1 to 2 anemia at baseline, that is before starting treatment with talazoparib. So, we knew that if you mandate dose reduction, a lot of patients will not get adequate dosing of talazoparib. So, we waited for grade 3 anemia and then instituted dose reduction. And that I thought personally was a good strategy because the grade 3 anemia happened after a median duration of three months, 3.3 months to be more precise. And then, these patients underwent protocol-mandated dose reduction, following which the dose discontinuations were quite low actually. Only 8.3% patients discontinued talazoparib because of anemia, and the median dose intensity or median relative dose intensity of talazoparib in the talazoparib arm remained quite high at more than 80%, which translates to a talazoparib dose of 0.4 milligram daily when the starting dose was 0.5 milligram. So those were the hallmark of toxicities. I do like to mention that those grade 3, 4 toxicities which are more known to affect the quality of life of our patients, such as grade 3, 4 anorexia, fatigue, nausea and vomiting, they were quite rare, happening in 1 to 4% patients who were on talazoparib. So overall, regarding the side effects, they were manageable, there were no new safety signals, and we could maintain adequate talazoparib dosing with dose reduction, which happened quite early during the protocol treatment. Dr. Christian Kollmannsberger: Thank you, Neeraj. Very impressive results indeed. The patient population included in TALAPRO-2 was very similar to those included in the PROpel phase 3 trial, which tested the combination of abiraterone and olaparib in the first-line mCRPC setting. So, I'd like to just mention that we also saw LBA16 on the PROpel study, which was the final overall survival in PROpel, which was presented by Noel Clarke. So PROpel, as you know, was a randomized phase 3 trial evaluating efficacy and safety of olaparib plus abiraterone versus placebo plus abiraterone as first-line therapy for mCRPC in the first-line metastatic castration resistance setting. The enrollment in that study was independent of known defects in the homologous recombination repair gene pathway in contrast to other studies, such as MAGNITUDE, which tested the biomarker upfront. A total of 796 patients were randomly assigned to either olaparib plus abiraterone or placebo plus abiraterone. And we saw similar results, significant radiographic progression-free survival with olaparib plus abiraterone in PROpel, which was the primary endpoint similar to TALAPRO-2, and that was published last year in the New England Journal of Medicine Evidence. Now, this abstract presented here at ASCO GU reported on overall survival with an overall survival majority of 47.9% and showed that with the addition of the PARP inhibitor olaparib to abiraterone, a statistically non-significant but clinically meaningful improvement in overall survival of about seven months were achieved compared to standard of care in abiraterone alone. The numbers were 42.1 versus 34.7 months in the all-comers population of patients in the first-line mCRPC setting. Importantly, I think the median overall survival of more than 42 months really represents the longest reported median overall survival thus far in a phase III trial for first-line metastatic castration-resistant prostate cancer. Although the median overall survival for the non-HRR group remains not statistically significant, with a hazard ratio of 0.89. Dr. Neeraj Agarwal: Such a great synopsis of the PROpel result data. Thank you, Christian, for highlighting these results. As we know, the combination is already approved by the EMA, the European Medical Agency, for patients in the first-line mCRPC setting who are not candidates for docetaxel chemotherapy. If this combination is approved by the FDA, we may have one more therapeutic option for our patients in first-line mCRPC. So, just continuing on the PARP inhibitors, there was one more oral presentation with PARP inhibitor rucaparib by Dr. Alan Bryce from the Mayo Clinic, Arizona. This was Abstract 18 on the primary result of the TRITON3 trial. So to complete our PARP inhibitor section, I would like to summarize the result of the TRITON3 trial, which was a randomized phase III trial evaluating rucaparib versus physician choice, which notably included docetaxel in addition to abiraterone or enzalutamide in patients with chemotherapy-naive mCRPC with BRCA1, BRCA2 or ATM alterations. These patients had disease progression after having one novel hormonal therapy, or we call them second-generation androgen pathway inhibitors in any setting. So these patients had to have disease progression on a novel hormonal therapy. In the BRCA subgroup and the subsequent intention to treat the population, the primary endpoint tested first was radiographic progression-free survival, and overall survival was the key secondary endpoint. The subgroup of patients with BRCA-altered disease had a median rPFS of 11.2 months with rucaparib compared to 6.4 months with physician choice of treatment - looks like almost doubling of the rPFS with the rucaparib. In the overall ITT population, median rPFS was 10.2 months with rucaparib and 6.4 months with the physician's choice of treatment. Although the overall survival data are immature, we still see a trend for improved overall survival with rucaparib. Regardless, the study clearly demonstrates the value of rucaparib for treating BRCA1 and BRCA2-altered mCRPC after disease progression on an androgen receptor pathway inhibitor. So these were the impressive results from the TRITON3 trial. But before we switch to non-prostate abstract, I would like to complete the prostate cancer discussion by talking about the Abstract 15, which was based on the results of the ARASENS trial presented by Dr. Maha Hussain. As we know, ARASENS is a randomized phase 3 trial evaluating the efficacy and safety of darolutamide plus androgen deprivation therapy plus docetaxel versus androgen deprivation therapy or ADT plus docetaxel. So the triplet of ADT plus darolutamide plus docetaxel being compared to ADT plus docetaxel chemotherapy in patients with newly diagnosed metastatic castration-sensitive prostate cancer. A total of 1,300 patients were randomly assigned to the doublet versus triplet. As presented in the last ASCO GU meeting exactly one year ago, the primary endpoint of the study was met with a significant improvement in overall survival and a 32% reduction in risk of death for patients on the triplet therapy with ADT plus docetaxel plus darolutamide versus ADT plus docetaxel chemotherapy. So triplet therapy was already approved based on these data. The abstract presented by Dr. Hussain this year is a post-talk analysis where Dr. Hussain and colleagues investigated the impact of triplet therapy across patients with high volume versus low volume per chartered criteria and higher risk versus low risk using latitude trial criteria. And investigators knew that these results would be highly attractive to practicing oncologists who are now choosing treatment based on volume of disease or risk of disease, more commonly, volume of disease. So, let's come to what was presented this ASCO GU. So, after 1,305 patients in ARASENS, the majority had high-volume disease and high-risk disease. Among patients with high-volume disease, the addition of darolutamide reduced the risk of death by 30% compared with ADT and docetaxel, with a hazard ratio of 0.69. In the risk groups, the addition of darolutamide seems to favor both high-risk and low-risk groups. Among patients with low-volume disease, there was a trend towards improvement in overall survival with the addition of darolutamide, but it did not reach statistical significance. The great news was that there was no new safety signal. So, to summarize these data, the triplet of darolutamide plus ADT plus docetaxel showed superior overall survival compared to doublet of ADT plus docetaxel, with an important caveat that triplet was not compared with any of the modern doublets of ADT plus a second generation androgen receptor pathways inhibitor such as abiraterone, apalutamide, or enzalutamide, or even darolutamide. So, I wish there was a third arm of ADT plus darolutamide. Having said that, triplet can be considered a standard of care now based on these data for patients with metastatic hormone sensory prostate cancer, where we would be using ADT plus docetaxel chemotherapy. And from this meeting data, this efficacy of triplet can be applied to high-volume disease and all risk disease. And we just need more time to see how the data pans out in low-volume patients with metastatic hormone-sensitive prostate cancer. Dr. Christian Kollmannsberger: Yes, I completely agree, Neeraj. I think all the data presented in these abstracts are really impressive and will impact our daily clinical practice and our patients more or less immediately. I think the use of PARP inhibitors, whether as a monotherapy or in combination with androgen receptor pathway inhibitors, as well as now the option of triplet therapy in the metastatic castration sensitive setting really offer patients with metastatic prostate cancer new treatment strategies and most importantly, improved survival outcomes. And it is impressive to see how we have pushed the prognosis and the outcomes for our patients with prostate cancer, I would say, in the last five to ten years. And similar to last year, I think the entire Prostate Cancer Day at ASCO GU 2023 was full with impressive data and featured dynamic content throughout the day. Dr. Neeraj Agarwal: Indeed. So, let's move on to bladder cancer. Christian, what are your key takeaways from the bladder cancer studies presented at the meeting? Dr. Christian Kollmannsberger: I think there were interesting abstracts in both the non-muscle-invasive and the muscle-invasive setting and the metastatic setting. So, for example, Abstract 442 was presented by Dr. Andrea Necchi on the cohort B of the phase 2 KEYNOTE-057 trial. As a background here, the standard treatment for high-risk non-muscle-invasive bladder cancer involves transurethral resection of the bladder tumor, a TURBT, followed by intravesical BCG therapy to eradicate any residual disease. And patients who fail to adequately respond to BCG are usually recommended to undergo radical cystectomy. So in the cohort B of the phase 2 KEYNOTE-057 trial that investigated the safety and efficacy of pembrolizumab as a single agent for patients with BCG-unresponsive, high-risk non-muscle-invasive bladder cancer who were ineligible or declined to undergo radical cystectomy, enrolled patients received standard-dose pembrolizumab of 200 milligrams every three weeks for up to 35 cycles. So very common as we do it with other disease sites. And at a median follow-up of 45.4 months, the primary endpoints of disease-free survival at twelve months was 43.5%. The median disease-free survival duration was 7.7 months. These are encouraging results, and we should keep in mind that a radical cystectomy has immense impact on our patients' quality of life. So I think it is important that we do these trials. Now in order to address potential biases in this phase II trial, such as the underlying heterogeneity of transurethral resection of bladder tumor quality, and to obtain a more comprehensive understanding of pembrolizumab's efficacy relative to a particular control group, we need further evaluation of pembrolizumab in a randomized trial before we can really go for regulatory approval. But overall, I think for the first time in a long time that we seem to be able to move the needle in non-muscle-invasive bladder cancer. Dr. Neeraj Agarwal: Thank you, Christian, for this great overview. Could you please also share the findings presented by Dr. Matt Galsky on Abstract 443? Dr. Christian Kollmannsberger: Of course, Neeraj. Abstract 443, presented by Matt Galsky, reported the extended follow-up results from the CheckMate 274 trial, which looked at another very important field where we haven't made that much progress, which is the adjuvant setting. And CheckMate 274 examined adjuvant nivolumab compared to placebo for patients with high-risk resected muscle-invasive urothelial carcinoma. In this trial, nivolumab was given at 240 milligrams every two weeks or placebo every two weeks for up to one year of treatment. After following up with patients for a median of 36.1 months, the study found that those who received nivolumab had a median DFS of 22 months compared to only 10.9 months for those who received placebo among the ITT patients. So basically, a doubling of the DFS with the addition of adjuvant nivolumab. The results were particularly notable for patients with high PD-L1 expressions or PD-L1 expression of 1% or more, as those who are treated with nivolumab had a median DFS of 52.6 months, which was six times higher than the DFS in the control group where patients received placebo, which was only 8.4 months. And I think that is truly impressive. One year of adjuvant therapy with nivolumab continues to show a sustained disease-free survival benefit over a period of three years in both the ITT and the PD-L1-high patient population. In my view, these results reinforce the utility of nivolumab in the adjuvant urothelial carcinoma setting after surgery. And it will be interesting to see how the overall survival pans out in this study. So, Neeraj, moving on to kidney cancer, what were your key takeaways from these studies on kidney cancer presented in this meeting? Dr. Neeraj Agarwal: So, there were exciting results presented from multiple studies in this area as well. For example, Abstract 603 presented by Dr. Mauricio Burotto, senior author was, Dr. Toni Choueiri on the three-year follow-up from the phase 2 CheckMate-9ER trial. So, in this trial, patients were randomized one-to-one to nivolumab 240 milligrams every two weeks, plus cabozantinib 40 milligrams daily versus sunitinib 50 milligrams daily for four weeks, and it was a six-week cycle for sunitinib until disease progression or unacceptable toxicity. So this was the design of the phase 3 CheckMate-9ER trial. And after a median follow-up of three years, the benefit of nivolumab plus cabozantinib remained consistent with previous follow-ups. So, as we know, these data have been presented in the past, also published in the New England Journal of Medicine. But this meeting was a clear follow-up of these data. Notably, the median overall survival of patients treated with cabozantinib plus nivolumab in the ITT population, which included all favorable intermediate and poor IMDC score patients, was significantly improved at 49.5 months compared to 35.5 months in the sunitinib arm. It is so heartening to see that median overall survival breaching the four-year mark in our patients with metastatic RCC in a consistent fashion. We saw similar data with the combination of ipilimumab plus nivolumab recently. And as these trials are maturing, we are probably going to see more combinations breaching this four-year mark. So importantly, no new safety signals emerged with the additional follow-up in either arm. And I think these results provide further support for the use of cabozantinib plus nivolumab as a first-line treatment option for patients with metastatic or advanced renal cell carcinoma. Dr. Christian Kollmannsberger: Indeed, I think it is extremely impressive what we've seen over the last 15 years in metastatic kidney cancer, going from a median overall survival of about a year to now more than four years. I think that is a great achievement, and we can see it on a daily basis in our clinical practice. Now, before we wrap up, I would like to highlight another potentially practice-changing trial, LBA602, which titled, “Results from Phase 3 Study of 89Zr-DFO-Girentuximab for PET/CT Imaging of Clear Cell Renal Cell Carcinoma: The ZIRCON Trial” presented by Dr. Brian Shuch. The background of this is that the detection of renal masses poses a challenge due to the limitations of diagnostic options such as imaging and biopsy. And we often, in clinical practice, are confronted with "What exactly is this?" And what's even more importantly, “What's the histology of this?” And a non-invasive, accurate method is needed for pre-treatment risk stratification. Girentuximab, a monoclonal antibody that targets carbonic anhydrase IX expressed on clear cell renal cell carcinoma, can obviously now aid in the differentiation between clear cell renal cell carcinomas and other renal lesions when radiolabeled with this new agent. The ZIRCON trial was open-label and designed to include patients with renal masses up to 7 cm in size or clear tumor stage cT1 who were scheduled for partial nephrectomy within 90 days of planned TLX250-CDx administration. The enrolled patients received a single intravenous dose of girentuximab on day 0 and underwent FDG PET/CT imaging on day 5 before their scheduled surgery. And the co-primary endpoints were to assess the sensitivity and specificity of girentuximab PET/CT imaging for detecting clear cell renal cell carcinoma in patients with indeterminate renal masses, with histology as the reference standard, which I think is a great way to test these agents because you get 100% validation. In the primary analysis of 284 patients, the average sensitivity and specificity across all three central readers were 86% and 87%, respectively, exceeding the prespecified thresholds. The positive and negative predictive values were 93.4% and 78%, respectively. And with very few related adverse events reported, the study affirms that girentuximab PET/CT is safe and effective in identifying clear cell renal cell carcinoma in patients with indeterminate renal masses. And the findings hold potential for developing optimal management strategies for patients with indeterminate renal masses. I think this is important that we add a non-invasive method to this because we are confronted on a regular basis with patients who either cannot tolerate a biopsy or where the biopsy is indeterminate. And this could potentially be a great tool to help us with our pre-treatment planning of our treatment strategy. Dr. Neeraj Agarwal: Wow. So, it looks like a new PET scan using a unique tracer and antibody to detect the clear cell renal cell carcinoma with high specificity and sensitivity. It reminds me of drawing a crude analogy from the PSMA PET scan in prostate cancer. And hopefully, we will be able to use these newer scans that we call TLX250-CDx PET/CT scan. I hope they have a simpler name for this very soon. Or maybe follow up for patients who had kidney cancer, localized kidney cancer taken out by radical surgery, and then we are following them. And sometimes, we don't know if a small lung nodule is metastatic or not. And these kinds of imaging studies may help us down the line in monitoring those patients as well. So indeed, very exciting progress not only in the therapeutic area now but also in diagnostic fields at this GU ASCO. So with that, we have seen multiple abstracts on prostate, bladder, and kidney cancer with real impact on how we practice medicine. Thank you, Christian, for sharing your insight with us today. It is an exciting time in GU Oncology, and we appreciate you taking the time to contribute to the discussion. Thank you so much. Dr. Christian Kollmannsberger: Thank you, Neeraj, thank you for having me. And I completely agree it remains an exciting time in GU oncology. Dr. Neeraj Agarwal: And thank you to our listeners for joining us today. You will find links to the abstracts discussed today on the transcripts of this episode. Finally, if you value the insights that you hear on the ASCO Daily News Podcast, please take a moment to rate, review, and subscribe wherever you get your podcasts. Disclaimer: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Find out more about today's speakers: Dr. Neeraj Agarwal @neerajaiims Dr. Christian Kollmannsberger Follow ASCO on social media: @ASCO on Twitter ASCO on Facebook ASCO on LinkedIn Disclosures: Dr. Neeraj Agarwal: Consulting or Advisory Role: Pfizer, Bristol-Myers Squibb, AstraZeneca, Nektar, Lilly, Bayer, Pharmacyclics, Foundation Medicine, Astellas Pharma, Lilly, Exelixis, AstraZeneca, Pfizer, Merck, Novartis, Eisai, Seattle Genetics, EMD Serono, Janssen Oncology, AVEO, Calithera Biosciences, MEI Pharma, Genentech, Astellas Pharma, Foundation Medicine, and Gilead Sciences Research Funding (Institution): Bayer, Bristol-Myers Squibb, Takeda, Pfizer, Exelixis, Amgen, AstraZeneca, Calithera Biosciences, Celldex, Eisai, Genentech, Immunomedics, Janssen, Merck, Lilly, Nektar, ORIC Pharmaceuticals, crispr therapeutics, Arvinas Dr. Christian Kollmannsberger: None disclosed
As part of the 2022 Prostate Cancer Patient Conference, Dr. Thomas Hope discusses PSMA PET and functional imaging for prostate cancer. Series: "Prostate Cancer Patient Conference" [Health and Medicine] [Education] [Show ID: 38569]
As part of the 2022 Prostate Cancer Patient Conference, Dr. Thomas Hope discusses PSMA PET and functional imaging for prostate cancer. Series: "Prostate Cancer Patient Conference" [Health and Medicine] [Education] [Show ID: 38569]
As part of the 2022 Prostate Cancer Patient Conference, Dr. Thomas Hope discusses PSMA PET and functional imaging for prostate cancer. Series: "Prostate Cancer Patient Conference" [Health and Medicine] [Education] [Show ID: 38569]
As part of the 2022 Prostate Cancer Patient Conference, Dr. Thomas Hope discusses PSMA PET and functional imaging for prostate cancer. Series: "Prostate Cancer Patient Conference" [Health and Medicine] [Education] [Show ID: 38569]
As part of the 2022 Prostate Cancer Patient Conference, Dr. Thomas Hope discusses PSMA PET and functional imaging for prostate cancer. Series: "Prostate Cancer Patient Conference" [Health and Medicine] [Education] [Show ID: 38569]
As part of the 2022 Prostate Cancer Patient Conference, Dr. Thomas Hope discusses PSMA PET and functional imaging for prostate cancer. Series: "Prostate Cancer Patient Conference" [Health and Medicine] [Education] [Show ID: 38569]
As part of the 2022 Prostate Cancer Patient Conference, Dr. Thomas Hope discusses PSMA PET and functional imaging for prostate cancer. Series: "Prostate Cancer Patient Conference" [Health and Medicine] [Education] [Show ID: 38569]
In this episode of BackTable Urology, Dr. Aditya Bagrodia interviews Dr. David Penson, professor and chair of urologic oncology at Vanderbilt University, about the indications and benefits of surgery for high risk prostate cancer. --- SHOW NOTES First, Dr. David Penson gives the traditional definition of high-risk prostate cancer, which is a PSA level over 20 ng/mL, a Gleason grade greater than 10, and a cancer staged at T2 or higher. However, he notes that in recent years, a more heterogeneous criteria has developed, so some patients with a Gleason grade greater than 8 and a T3 stage can also be considered high risk. Dr. Penson believes that pathological analysis is the best criteria to use when assessing risk and also uses MRI to distinguish between T2 and T3 patients and look for the median lobe before surgery. In his personal experience, he has noted that some patients will find online information about prostate cancer as a relatively benign chronic disease. For patients with high risk cancer, it is important to emphasize that the conventional active surveillance approach for low risk prostate cancer will not be beneficial. Both doctors agree that sending their patients curated, quality information is important and recommend using the WellPrept app. The doctors also discuss different imaging modalities involved in staging, such as PSMA PET scan, a bone scan, and prostate MRI. Before surgery, patients may receive neoadjuvant treatment. In the past, GnRH agonists were used, but long term data showed that patients receiving this type of therapy in addition to surgery had the same recurrence rate as patients who underwent surgery alone. Recently, newer neoadjuvant treatments, like PARP inhibitors, have been developed. Next, Dr. Penson speaks about choosing surgery versus radiation therapy (RT) as a primary treatment. The main risk of prostatectomy is its impact on continence and sexual dysfunction. The downside of radiation therapy is that the possibility of surgery as a therapeutic option is eliminated and its side effects, such as irritating urinary symptoms. Dr. Penson also notes that nerve sparing prostatectomies may be cancer sparing. In his opinion, if patients have impotence at baseline, nerve sparing surgery is not beneficial because of the risk of leaving positive margins. Contraindications to surgery include rectal involvement, a history of multiple abdominal surgeries, severe heart disease, bladder neck involvement, and a high volume nodal disease. Ideal prostatectomy patients are ones who have high grade disease contained in the prostate (T2) and patients with preexisting lower urinary tract symptoms (LUTS). Finally, the doctors discuss the use of nomograms to determine the extent of cancer control and the need for additional therapy. Dr. Penson has limited use for nomograms. He believes that they can generally be used to predict mortality, but not cure rates. He prefers to base prognosis on postoperative results. If the postoperative pathology report comes back with widely positive margins or bladder neck involvement, he discusses RT as an adjuvant treatment with his patients. For this reason, he emphasizes the need for collaboration with radiation oncologists and multidisciplinary tumor boards. --- RESOURCES WellPrept App: https://wellprept.com/
Featuring perspectives from Dr Matthew Smith, including the following topics: Introduction: Abemaciclib for Prostate Cancer? (0:00) Case: A man in his early 70s with a PSA of 150 ng/mL, Gleason 4 + 4 and upper abdominal adenopathy — Jennifer L Dallas, MD (9:30) Case: A man in his late 60s with Gleason 4 + 4, PSA of 147 ng/mL and a negative CT — David S Morris, MD (34:30) Case: A man in his late 60s with coronary artery disease and Gleason 4 + 4 who underwent external beam radiation therapy (EBRT) in 2013 and now has increasing PSA of 3.8 with a 6-month doubling time — Gurveen Kaur, MD (37:56) Case: A man in his mid 60s who experiences M0 progression after EBRT followed by androgen deprivation therapy (ADT) but refuses to continue ADT — Henna Malik, MD (41:44) Case: A man in his early 50s with a slowly rising PSA (now 1.31) after radical prostatectomy and salvage radiation therapy; PSMA PET scan denied by insurance, now appealed — Kapisthalam (KS) Kumar, MD (50:23) Case: A man in his late 70s with Gleason 5 + 4 and a PSA of 23 ng/mL increasing after EBRT followed by ADT, cryoablation and enzalutamide; after a response, 18F-fluciclovine PET shows subtle focus of uptake in left prostate — Susmitha Apuri, MD (57:06) CME information and select publications
How do we move forward with prostate imaging? In today's episode of Theragnostic Talks, live from the EANM'22 Congress in Barcelona, we focus on PSMA-PET. How has PSMA-PET developed? Where are we regarding the diagnosis of prostate cancer? And how can we use PSMA-PET as a diagnostic tool for other forms of malignant tumours? Our thanks to Prof. Helle Damgaard Zacho, Dr. Daniela Oprea-Lager, and Simona Malaspina for sharing your expertise with us. Guests: Prof. Helle Damgaard Zacho, Dr. Daniela Oprea-Lager and Simona Malaspina. By: Gustav Widar, Medical Affairs Manager at SAM Nordic Contact us: podcast@samnordic.se For more information: www.samnordic.se
In this podcast, Dr. Jeff Twidwell, a urologist (retired) and Dr. Jim Lehmann, an internist (retired) join the podcast to discuss various aspects of prostate cancer from a unique personal and professional viewpoint. Enjoy the podcast. Objectives:Upon completion of this podcast, participants should be able to: Describe prostate specific antigen and what levels are considered normal. Identify when to include PSA testing and to what specific patient populations. Determine when a referral to a urologist is needed for further patient evaluation. CME credit is only offered to Ridgeview Providers & Allied Health Staff for this podcast activity. Complete and submit the online evaluation form, after viewing the activity. Upon successful completion of the evaluation, you will be e-mailed a certificate of completion within approximately 2 weeks. You may contact the accredited provider with questions regarding this program at Education@ridgeviewmedical.org. To receive continuing education credit for this activity - click the link below, to complete the activity's evaluation. CME Evaluation (**If you are listening to the podcasts through iTunes on your laptop or desktop, it is not possible to link directly with the CME Evaluation for unclear reasons. We are trying to remedy this. You can, however, link to the survey through the Podcasts app on your Apple and other smart devices, as well as through Spotify, Stitcher and other podcast directory apps and on your computer browser at these websites. We apologize for the inconvenience.) DISCLOSURE ANNOUNCEMENT The information provided through this and all Ridgeview podcasts as well as any and all accompanying files, images, videos and documents is/are for CME/CE and other institutional learning and communication purposes only and is/are not meant to substitute for the independent medical judgment of a physician, healthcare provider or other healthcare personnel relative to diagnostic and treatment options of a specific patient's medical condition; and are property/rights of Ridgeview Medical Center & Clinics. Any re-reproduction of any of the materials presented would be infringement of copyright laws. It is Ridgeview's intent that any potential conflict should be identified openly so that the listeners may form their own judgments about the presentation with the full disclosure of the facts. It is not assumed any potential conflicts will have an adverse impact on these presentations. It remains for the audience to determine whether the speaker's outside interest may reflect a possible bias, either the exposition or the conclusions presented. Ridgeview's CME planning committee members and presenter(s) have disclosed they have no significant financial relationship with a pharmaceutical company and have disclosed that no conflict of interest exists with the presentation/educational event. Thank-you for listening to the podcast. SHOW NOTES: *See the attachment for additional information. Diagnosis - Call to action - "I will not miss a case of cancer of the prostate." (Dr. Jim Lehmann) - Main risk factors: age, black/hispanic ethicity, genetics - Evidence based moment (see show note attachment for link to referenced article)Screening- PSA (prostate specific antigen) - level greater than 4.0 ng/ml is "abnormal" - Age adjustment - PSA levels reduced with 5-alpha reductase inhibitor - PSA increases 0.75 ng/ml per year - Stop screening when life expectancy is less than 10 years - Shared decision making Next Steps in Diagnosis- Biopsy (template and MRI) - MRI - 4K score blood test - Ultrasound - Gleason score and grade - Decipher testing - PSMA-PET scan Prostate Cancer Care Team - Urologists - Primary Care - Radiation oncology - Oncology Treatment- Observation - Surgery (open, DaVinci, Laparoscopy) - Radiation - Hormonal (androgen deprivation) - Cryosurgery - Brachytherapy (prostate radioactive seeds) - Chemotherapy - Immunotherapy (advanced prostate cancer) - Proton therapy (up and coming) Thanks for listening.Please check out the additonal show notes for additional resources.
On this episode host Jonathan Chance talks with Dr. Peter Rossi, who is a radiation oncologist at the Calaway Young Cancer Center in Glenwood Springs, Colorado. He is also the current President of the American Brachytherapy Society - ABS. Dr. Rossi talks about the mission of the ABS and their roll in providing prostate cancer patients with information about Brachytherapy. Dr. Rossi also provides important information about the, PSMA, PET imaging scan that many doctors are now using to detect the presence of prostate cancer cells. For more information about prostate cancer, men's health and Jonathan's new book Unaware, which is about his battle with prostate cancer visit: https://www.iknowmypsa.org
Rahul Tendulkar, MD, radiation oncologist at Cleveland Clinic Cancer Center, joins the Cancer Advances podcast to talk about the PSMA PET scan for patients with prostate cancer. Listen as Dr. Tendulkar explains the benefits and how the scan is changing the way we think about and treat prostate cancer.
LuTectomy – LuPSMA in the very early stage of prostate cancer – what were the initial results? What difference does it make, choosing the right PSMA tracer? And how should PSMA-PET be used, according to the radiation oncologist? Listen to our eminent guests Declan Murphy, Stefano Fanti, Louise Emmett, Gert de Meerleer and Ken Herrmann talking about the future of theragnostics in urology, from the EAU 22 Congress in Amsterdam. Guests: Ken Herrmann, Gert de Meerleer, Louise Emmett, Stefano Fanti and Declan Murphy. By: Lisa Gruschy and Gustav Widar Contact us: podcast@samnordic.se For more info, visit www.samnordic.se
Phillip Kuo discusses the biomarker to select patients for therapy.
Guest host Dr. Neeraj Agarwal, of the University of Utah Huntsman Cancer Institute and the ASCO Daily News editor-in-chief, discusses key therapeutic advances in mRCC and mUC, as well as new research that proposes periodic scans to monitor patients with mCSPC for disease progression, with Dr. Jeanny-Aragon-Ching of the Inova Schar Cancer Institute. Transcript: Dr. Neeraj Agarwal: Hello and welcome to the ASCO Daily News podcast. I'm Dr. Neeraj Agarwal, the director of the Genitourinary Oncology Program, a professor of medicine at the University of Utah Huntsman Cancer Institute, and editor-in-chief of the ASCO Daily News. My guest today is Dr. Jeanny Aragon-Ching, who is a medical oncologist and the Clinical Program Director of Genitourinary Cancers at the Inova Schar Cancer Institute in Virginia. Today, we will be discussing key posters in genitourinary (GU) oncology that will be featured at the 2022 ASCO Annual Meeting. Our full disclosures are available in the show notes and disclosures of all guests on the podcast can be found on our transcripts at asco.org/podcast. Jeanny, it is great to have you on the podcast today. Dr. Jeanny Aragon-Ching: Thanks, Neeraj. It's a pleasure for me to be here as well. Dr. Neeraj Agarwal: Jeanny, let's begin with Abstract 4510. This is a trial that represents a growing interest among researchers worldwide in the microbiome and how it is impacted by antibiotics and how it modulates immune checkpoint inhibitor response. Can you tell us about this study? Dr. Jeanny Aragon-Ching: Thanks, Neeraj, I would be happy to. So, the title of the abstract is, “Characterization of the Microbial Resistome in a Prospective Trial of CBM 588 in Metastatic Renal Cell Carcinoma Offers Mechanism for Interplay Between Antibiotic Use and Immune Checkpoint Inhibitor Activity.” So, this is an interesting abstract that originated likely from the observation that getting antibiotics while on checkpoint inhibitors typically results in worse outcomes, perhaps because antibiotics can clear the normal gut flora and thereby increase these pathogenic antibiotic-resistant bacteria. Now, on the other hand, there were some retrospective studies using a live microbial product called CBM 588, which seems to improve outcomes in patients on checkpoint inhibitors and getting antibiotics. So, the idea, therefore, is that shifting the genes encoding antimicrobial resistance could result in a better checkpoint inhibitor response. So, this Abstract 4510 is a small study conducted by Dr. Nazli Dizman and Dr. Sumanta (Monty) Kumar Pal, and colleagues, and enrolled 29 metastatic clear cell RCC patients with intermediate or poorest disease. And they were stratified into receiving either nivolumab or ipilimumab compared to nivo/IPI with CBM 588. Now stool samples were collected at baseline in week 12. And they did this whole metagenome sequencing to analyze a stool microbiome composition, and they also looked at the antibiotic resistance genes for the most common classes of antibiotics. The results showed an astounding improvement in objective responses. So, 58%, for instance, in nivo/IPI and the CBM 588 arm compared to only 20% in the nivo/IPI arm. And it seems like also the antibiotics resistance genes were also decreased in those getting the CBM 588 alongside nivo/IPI. Therefore, responses were improved by shifting the gut microbiome alone. So, these findings were published actually recently by these authors in Nature Medicine. So, in case anyone wants to take a deep dive, it would be a good interesting read for this dataset. Dr. Neeraj Agarwal: Very interesting, indeed. Jeanny, what is the main message here for our colleagues? Dr. Jeanny Aragon-Ching: I think, Neeraj, the key takeaway message is that this is a very provocative proof of concept trial that suggests shifting the gut microbiome has the potential to improve responses to checkpoint inhibitors and outcomes. So, this is a very up-and-coming trial and is seen also across the board in other cancers. Dr. Neeraj Agarwal: Thanks, Jeanny. Moving on to urothelial cancer, there is a poster that I think is a must-see for our colleagues. This is Abstract 4577 titled, “Defining Platinum Ineligible Patients with Metastatic Urothelial Carcinoma.” Dr. Jeanny Aragon-Ching: So, Neeraj, what can you tell us about this abstract? Dr. Neeraj Agarwal: So, over the past few years, there has been a tremendous evolution in the treatment landscape for patients with metastatic urothelial carcinoma. For over 40 years the standard of care for these patients has been cisplatin-based chemotherapy. However, approximately 50% of patients are cisplatin-ineligible, due to underlying comorbidities, and are offered carboplatin as an alternative. So, although the checkpoint inhibitors pembrolizumab and atezolizumab were approved as first-line therapy for these patients in 2017, the U.S. Food and Drug Administration (FDA) has now restricted the use of first-line pembrolizumab to platinum ineligible patients with metastatic urothelial carcinoma. The challenge we face as oncologists since the FDA restriction is the absence of a formal definition of platinum ineligibility and the inclusion of this definition in the guidelines. So, in Abstract 4577, Drs. Shilpa Gupta and Jonathan Rosenberg, along with the team present an updated consensus definition for platinum ineligibility based on an online survey of 60 genitourinary oncologists in the United States. Based on the results from this survey, any patient with metastatic urothelial carcinoma, meeting 1 of the following 5 clinical and or laboratory parameters should be considered platinum ineligible, and these are 1 of the following: an ECOG performance status of 3 or more, creatinine clearance of fewer than 30 mils per minute, or peripheral neuropathy of grade 2 or more, or heart failure class of 3 or more—so, this is NYHA heart failure class of 3 or more—and lastly, the combination of performance status of 2 or more, plus a creatinine clearance of less than 30 mils per minute. Dr. Jeanny Aragon-Ching: Well, this is a timely update, Neeraj. So, what do you think is a key takeaway from this abstract? Dr. Neeraj Agarwal: These criteria based on simple and easily available clinical and or laboratory parameters will now allow us to readily define platinum ineligibility in our patients with metastatic urothelial carcinoma, which is a need in busy clinics, both in academic and community settings. So, I think once published and obviously once endorsed by guidelines, we really would like to be able to use this criterion to quickly define platinum ineligibility in our clinics. Dr. Jeanny Aragon-Ching: Agree. Yeah. Dr. Neeraj Agarwal: So, Jeanny, let me switch the gears. PSMA testing is a hot topic this year. And there is an abstract that could potentially have an impact on future guidelines, and how we will practice further down the road. So, I'm referring to the Abstract 5088 titled, “Predictive Value of Extra Prostatic Disease Detection by Preoperative PSMAPET for Biochemical Recurrence-free Survival in Patients with Otherwise Localized Prostate Cancer and Who are Treated with Radical Prostatectomy.” So, this is a follow-up analysis of a multicenter prospective phase 3 imaging trial. So, could you please tell us more about this abstract where they are using PSMA PET scan in the preoperative localized prostate cancer setting? Dr. Jeanny Aragon-Ching: Absolutely, Neeraj. So, you may recall that the multicenter prospective phase 3 imaging trial that garnered gallium PSMA approval by the FDA was actually based on this study that looked at the intermediate and high-risk patients with prostate cancer undergoing radical prostatectomy and lymph node dissection, and they underwent prior gallium PSMA PET scanning for pelvic nodal metastases prior to surgery. So, this was actually previously reported by Dr. Calais and group. Now they are reporting on Abstract 5088 as a post hoc analysis of the same population and group of patients looking for extraprostatic disease. And the final pathology was also correlated to look at nodal disease in these patients in order to predict biochemical recurrence, so they follow these patients for biochemical recurrence occurrence. So, of the 36% of patients who did undergo radical prostatectomy after they underwent PSMA PET scan, about 41% of them recurred with biochemical recurrence, and 40% of them underwent some kind of salvage therapy or some treatment. What was very interesting was when they looked at the biochemical recurrence-free survival. It was better in those who were PSMA negative, and that recurrence-free survival was easily about 33 months, compared to only about 7.3 months in those who were PSMA-positive scans. Furthermore, the ones who had the longest and the highest biochemical recurrence-free survival, intuitively, were those who were node-negative and PSMA PET-negative, so probably not surprisingly. And that rate was about 46 months—close to 4 years. Whereas those who are node-positive on final pathology and their PSMA PET was also positive, they only had about 3 months of biochemical recurrence-free survival. Dr. Neeraj Agarwal: Very interesting. So, it looks like the PSMA PET scan is predicting biochemical recurrence-free survival in localized prostate cancer settings. So, Jeanny, what is the key takeaway from this trial? Dr. Jeanny Aragon-Ching: I think, Neeraj, the bottom line is that patients with extraprostatic disease that is detected by their preoperative PSMA PET scan does predict strongly a high risk of biochemical relapse, and this can really be an additional tool that clinicians can use to help inform and guide future therapy. Dr. Neeraj Agarwal: Thanks, Jeanny. The research on preoperative PSMA testing and its implications on future treatment strategies in the setting is going to be really interesting to watch in the very near future. Dr. Jeanny Aragon-Ching: Yes, absolutely. I really think we should also discuss Abstract 5072, along those lines, the importance really of radiographic monitoring for disease progression in patients with metastatic hormone-sensitive prostate cancer. Dr. Neeraj Agarwal: Yes, thanks for reminding and this is Abstract 5072. This is a post hoc analysis of the ARCHES trial, titled, “Radiographic Progression in the Absence of PSA Progression in Patients with Metastatic Hormone-sensitive Prostate Cancer.” During the last several years, we have seen many of these agents typically given for gastric resistant prostate cancer moving upfront to the castration-sensitive prostate cancer setting. This is especially true for androgen receptor access targeting agents such as abiraterone, enzalutamide, and apalutamide, all being now approved for patients with metastatic castration-sensitive prostate cancer. What is noteworthy from all these trials, and is reported in Abstract 5072, is the use of imaging studies to evaluate disease progression. So, in Abstract 5072, Dr. Andrew Armstrong and Dr. Arun Azad performed a post hoc analysis of the ARCHES trial to investigate the concordance between radiographic progression and the PSA Progression as defined by PCWG2 criteria, or between radiographic progression and any rise in the PSA above nadir, in patients who were being treated with this novel hormonal therapies, in this case, enzalutamide for metastatic castration sensitive prostate cancer. And as a quick reminder, ARCHES was a phase 3 trial that showed a significant reduction and radiographic progression-free survival and improved overall survival for patients with metastatic castration sensitive prostate cancer treated with enzalutamide plus androgen deprivation therapy (ADT) versus those treated with placebo plus androgen deprivation therapy. So, very interestingly, the findings from this study indicate that 67% of patients on the enzalutamide plus ADT arm did not have [Prostate Cancer Clinical Trials Working Group 2 criteria] PCWG2-defined prostate-specific antigen (PSA) progression at the time of radiographic progression. And discordance was present in the ADT-only arm as well, where they found 42% of patients on the ADT-only arm had radiographic progression but did not have PCWG2-defined PSA progression. Interestingly, this discordance of radiographic disease progression was also seen with any rise in the PSA above nadir. And I personally found this information to be very clinically relevant when we are seeing the majority of patients actually experiencing radiographic disease progression, not experiencing PSA progression at the same time. Dr. Jeanny Aragon-Ching: Yeah, absolutely. I agree with that, Neeraj. So, very interesting data. So, what do you think is the key takeaway message for the clinicians listening to us? Dr. Neeraj Agarwal: I'll make the message very simple. I think the message is that patients with metastatic castration-sensitive prostate cancer need to be monitored for disease progression with periodic scans, and PSA monitoring alone is not sufficient in the majority of these patients. Again, we cannot undervalue the role of periodic imaging studies in these patients so that we can timely diagnose them to have disease progression. Dr. Jeanny Aragon-Ching: I agree with that. Dr. Neeraj Agarwal: Jeanny, the last abstract I would like to mention before we wrap up the podcast is Abstract 4509, the results from the phase1 live SPARC 001 study. So, can you please tell us more about this study titled, “Phase-1 Live SPARC 001: The Study of Belzutifan in Advanced Solid Tumors,” which is an update of the renal cell carcinoma cohort with more than 3 years of total follow up? Dr. Jeanny Aragon-Ching: Thanks, Neeraj. So, while the current therapeutic landscape for patients with metastatic clear cell renal cell carcinoma (RCC) has changed dramatically over the past several years, with significant improvement in patient outcomes. Most patients unfortunately still experience disease progression on current treatments. So, in-depth molecular profiling of clear cell RCC has revealed recurrent loss of function mutations in VHL in actually greater than 90% of patients. So, the VHL protein, as you will recall, is part of the oxygen-sensing pathway, regulating levels of HIF which is hypoxia-inducible factor protein, it's a transcriptional activator that mediates the response to hypoxic conditions. So, HIF-2α is a key oncogenic driver in RCC. So, previous data you may recall from the phase-1 Live SPARC 001 trial was designed to evaluate belzutifan so, this was a novel HIF-2α inhibitor which showed durable anti-tumor activity and acceptable safety profile in patients with metastatic clear cell RCC. So, in Abstract 4509, Drs. Jonasch and Toni Choueiri presented updated results from this trial after more than 3 years of follow-up. Of the 55 patients enrolled 16% of patients remained in treatment. And 62% of patients had discontinued treatment because of, unfortunately, disease progression. The median progression-free survival (PFS) for the total cohort was 14.5 months. And the overall disease control rate was 80%. Forty percent of patients experienced grade 3 treatment-related adverse events with the most frequent ones being anemia and hypoxia. There were no great 4 or 5 treatment-related adverse events. And these results, therefore, show that belzutifan monotherapy continues to show a high rate of disease control and a safety profile in a heavily treated population of patients with metastatic RCC. So, it is great to see that there were no new safety signals. Dr. Neeraj Agarwal: Very nice data indeed. So, Jeanny, what is the key takeaway message here for our listeners? Dr. Jeanny Aragon-Ching: Yeah, I think the message here is that the use of belzutifan monotherapy continues to show efficacy and safety in patients with metastatic clear cell RCC, which have progressed on multiple prior contemporary therapies, and there are phase 3 trials currently underway. Dr. Neeraj Agarwal: Jeanny, any final thoughts before we wrap up the podcast today? Dr. Jeanny Aragon-Ching: Thanks, Neeraj. I think it's a really exciting time to be in genitourinary (GU) oncology, and I'm truly looking forward to seeing some great sessions at the 2022 ASCO Annual Meeting. Dr. Neeraj Agarwal: Thank you, Jeanny, for sharing your insight with us today. It was a great conversation. And thank you to our listeners for joining us today. You will find links to the abstracts discussed today on the transcript of this episode. Finally, if you value the insights that you hear on the ASCO Daily News podcast, please take a moment to rate, review, and subscribe wherever you get your podcast. Disclosures: Dr. Neeraj Agarwal: Consulting or Advisory Role: Pfizer, Bristol-Myers Squibb, AstraZeneca, Nektar, Lilly, Bayer, Pharmacyclics, Foundation Medicine, Astellas Pharma, Lilly, Exelixis, AstraZeneca, Pfizer, Merck, Novartis, Eisai, Seattle Genetics, EMD Serono, Janssen Oncology, AVEO, Calithera Biosciences, MEI Pharma, Genentech, Astellas Pharma, Foundation Medicine, and Gilead Sciences Research Funding (Institution): Bayer, Bristol-Myers Squibb, Takeda, Pfizer, Exelixis, Amgen, AstraZeneca, Calithera Biosciences, Celldex, Eisai, Genentech, Immunomedics, Janssen, Merck, Lilly, Nektar, ORIC Pharmaceuticals, crispr therapeutics, Arvinas Dr. Jeanny Aragon-Ching: Honoraria: Bristol-Myers Squibb, EMD Serono, Astellas Scientific and Medical Affairs Inc Consulting or Advisory Role: Algeta/Bayer, Dendreon, AstraZeneca, Janssen Biotech, Sanofi, EMD Serono, AstraZeneca/MedImmune, Bayer, Merck, Seattle Genetics, Pfizer, Immunomedics, Amgen, AVEO, Pfizer/Myovant, Exelixis Speakers' Bureau: Astellas Pharma, Janssen-Ortho, Bristol-Myers Squibb , Astellas/Seattle Genetics Travel, Accommodations, Expenses: Dendreon, Algeta/Bayer, Bristol Myers Squibb, EMD Serono, Astellas Pharma Disclaimer: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast expressed their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.
Not to be confused with “carcinoma of unknown primary,” in this episode of metastatic disease of “origin TBD”, we discuss the workup of a mass noted incidentally on imaging. This is a very high yield topic often faced on solid oncology consults! Major Points Covered:Mass found incidentally on imaging → we need to stage alwaysInitial Workup:Reasonable to get CBC, CMP, UA, PSA (if male)Low blood counts, maybe marrow involvementCr elevated concern for obstruction possiblyLFTs elevated concern for mass in the biliary/pancreas regionUA w/ hematuria → maybe bladderBut bottom line you're gonna get a scan, which scan to get though?Recommend referencing NCCN guidelines to determine additional staging scansCreate an account on nccn.org and look at guidelines by tumor typeNot all cancers require a PET/CT scanThere are newer modalities for imaging other than FDG PET including PSMA PET (prostate), Auxumin PET (prostate), and DOTATE PET (neuroendocrine)Certain cancers can be diagnosed on imaging alone (RCC and HCC)Some cancers require Brain MRI for stagingWhat to biopsy?FNA often adequate for solid tumors but may need core if non diagnostic Need core or ideally excisional if highly concerned for lymphomaAlways try to biopsy the site that will upstageDistant lymph nodes or other metastatic sitesWhat about tumor markers?We use this for treatment monitoring, not for diagnostic purposesImportant to establish a baseline to follow, special circumstances for diagnostic purposes to consider below:PSA in male if concerned about prostate cancerAFP helpful if concerned for HCC → liver masses in a cirrhoticAFP and b-HCG if concerned for testicular → young or middle aged male with mediastinal massMolecular testing not necessarily needed at the time of biopsy Please visit our website (TheFellowOnCall.com) for more information Twitter: @TheFellowOnCallInstagram: @TheFellowOnCallListen in on: Apple Podcast, Spotify, and Google Podcast
Guest host, Dr. Neeraj Agarwal, editor-in-chief of ASCO Daily News and director of the Genitourinary Cancers Program at the University of Utah's Huntsman Cancer Institute, and Dr. Jason Efstathiou, chair of the 2022 ASCO Genitourinary Cancers Symposium, discuss key abstracts and innovations in GU oncology featured at #GU22. Dr. Efstathiou is professor at Harvard Medical School and director of the Genitourinary Division in Radiation Oncology at Massachusetts General Hospital. Transcript Dr. Neeraj Agarwal: Hello, and welcome to the ASCO Daily News Podcast. I am Dr. Neeraj Agarwal, the director of the Genitourinary Program and professor of medicine at the University of Utah Huntsman Cancer Institute and editor in chief of the ASCO Daily News. Today we'll be discussing key advances in GU oncology featured at the 2022 ASCO Genitourinary (GU) Cancers Symposium. I'm delighted to welcome Dr. Jason Efstathiou, who was the chair of this year's GU ASCO meeting. Dr. Efstathiou is the professor at Harvard Medical School and the director of Genitourinary Division in Radiation Oncology and clinical co-director of The Claire and John Bertucci Center for GU Cancers at the Massachusetts General Hospital. Our full disclosures are available in the show notes and the disclosure of all guests on the podcast can be found on our transcript at asco.org/podcast. Jason, thank you for coming on the podcast today. Dr. Jason Efstathiou: Thank you very much, Neeraj. It's a real pleasure to be with you. Dr. Neeraj Agarwal: So, Jason, the GU meeting showcased some fantastic advances across the spectrum of GU malignancies, can you please tell us about some of the hot topics that made the headlines this year? Dr. Jason Efstathiou: Absolutely. This certainly was a dynamic and interactive hybrid ASCO GU meeting for all those attending in person, live streaming, or accessing the content on demand. With over 5,200 registrants this year, that's an actual record for this meeting and over 70 countries represented. This meeting truly serves as the premier global event for all those who diagnose, treat and study GU cancers. The meeting highlighted novel scientific and clinical findings that were high impacted. [And] in many cases will lead to practice changing care. The meeting had a real focus on diversity, global perspectives, enhanced interactivity, networking, multidisciplinary, collaborative, and evidence-based care. As you know, this year's theme was “World Class Science, Patient-Centered Care,” and this theme was highlighted throughout the program. The meeting kicked off with a rich day focusing on prostate cancer, lots on PSMA imaging, such as Abstract 9 and a very, very excellent session on PSMA targeting and beyond which explored opportunities and challenges with PSMA novel therapeutics, including biomarkers of response and mechanisms of resistance. Then Abstract 10 looked at PSMA PET and FDG PET as predictors of response and prognosis in a randomized phase 2 trial of Lutetium PSMA (177Lu-PSMA-617) vs cabazitaxel and metastatic castration-resistant prostate cancer (CRPC) progressing after docetaxel. And it suggested that Lutetium PSMA be prioritized in men with high PSMA expression. And this could actually be predictive. We had some awesome abstracts. Abstracts 222 and 223 suggested that a nozzle digital pathology-based biomarker developed using artificial intelligence is more effective than clinical prognostic markers for predicting long term outcomes in patients with prostate cancer. And that this AI tool can actually successfully guide the use of androgen deprivation therapy in men with intermediate risk localized prostate cancer. And then of course, there were some very exciting results in discussion with the primary results of 3 potentially practice-changing phase 3 trials in the setting of metastatic prostate cancer that were presented in the oral prostate session. These were: PROpel (Abstract 11), MAGNITUDE (Abstract 12), and the ARASENS trials (Abstract 13). Neeraj, as a practicing medical oncologist, what did you think of these 3 abstracts? Dr. Neeraj Agarwal: I agree with you, Jason. These are indeed practice-impacting, practice-changing abstracts, which was a record for a prostate oral session, all 3 abstracts. In fact, the results of the phase 3 trials are [likely] going to influence or impact our practice in coming months. I would like to start with Abstract 11 on the results of the PROpel trial. So, PROpel is a randomized phase 3 trial evaluating the efficacy and safety of olaparib plus abiraterone vs placebo plus abiraterone. In the first-line metastatic cast of resistant cluster cancer, docetaxel therapy was allowed for these patients if given in the metastatic castration sensitive prostate cancer setting. Enrollment in the study was independent of the defects in the homologous recombination repair gene pathway. The primary endpoint was investigator assessed radiographic progression-free survival with multiple secondary endpoints, including overall survival and safety. A total of 796 patients were randomly assigned to olaparib plus abiraterone or placebo plus abiraterone at the pre-plant interim analysis. Results show that with a significant improvement in the radiographic progression-fee survival for all patients receiving the combination therapy, regardless of the presence of homologous recombination repair gene mutations. Overall survival analysis is still immature with only 29% event having occurred thus far. It is interesting that even patients deemed a negative for homologous recombination repair gene mutations showed significant improvement in video graphic progression-free survival when treated with the combination of olaparib plus abiraterone versus placebo plus abiraterone. I would like to mention the MAGNITUDE trial, which is Abstract 12, in the same context, as these have very similar populations and combination regimens. So, MAGNITUDE is a randomized phase 3 trial evaluating the efficacy and safety of niraparib plus abiraterone vs placebo plus abiraterone in the first-line metastatic castrate resistant prostate cancer setting. The eligible patient population was slightly different from that in the PROpel trial—prior attacks in therapy or novel hormonal therapy in the metastatic castration sensitive prostate cancer or non-metastatic castrate resistant prostate cancer were allowed. Also, patients were eligible if they had received up to 4 months of abiraterone in the first-line metastatic CRPC setting. Prospective selection of the patients with, and without homologous recombination repair gene mutations was required. So, the primary endpoint was radiographic progression-free survival by central with multiple secondary endpoints, including overall survival and safety. A pre-specified early fragility analysis was planned after enrolling 200 patients who are [homologous recombination repair] (HRR) negative and who were randomly assigned to receive either niraparib plus abiraterone or placebo plus abiraterone. The pre-planned fertility analysis showed no benefit in the biomarker negative cohort. Four hundred and twenty-three patients who were HRR positive were randomly assigned to receive either the combination of niraparib plus abiraterone or placebo plus niraparib at the pre-planned interim analysis. The results show that trial method—primary endpoint with a significant improvement in the radiographic progression-free survival for BRCA1 and 2 patients—and all patients who are homologous recombination repair mutation positive [were] receiving the combination of niraparib plus abiraterone versus placebo plus niraparib. Overall survival reserve is still immature. My combined take on the PROpel and the MAGNITUDE trial, based on the data presented so far or available in the public domain so far, is that both trials establish that combination of a PARP inhibitor plus abiraterone on in the first-line settings for me, for [patients with] HRR mutation positive metastatic castration resistant prostate cancer [will] improve radiographic progression-free survival. Even though overall survival data immature for both trials, I expect both combinations will be approved by the U.S. Food and Drug Administration in the near future and will be available to our patients. The HRR negative in the PROpel trial also seemed to benefit with the combination of abiraterone plus olaparib. I'm looking forward to data on confirmation of HRR negative status by tissue-based genomic profiling results in the full-length publication, which we expect to be published soon. If indeed confirmed, I see the combination of abiraterone plus olaparib to be reasonable option for patients who are HRR negative in the first metastatic castration prostate cancer set. The last practice changing abstract in the oral prostate session was Abstract 13 on the results of the ARASENS trial. ARASENS is a randomized phase 3 trial evaluating the efficacy and safety of darolutamide plus ADT or androgen deprivation therapy plus docetaxel versus placebo plus ADT plus docetaxel in patients with metastatic castration sensitive prostate cancer or mCSPC. It is important to note that this study only included patients that were eligible for ADT plus docetaxel chemotherapy. The primary endpoint was overall survival with multiple secondary endpoints, including time to casted resistance, time to pain progression, time to first symptomatic skeletal event, and time to start of next antineoplastic therapy and of course, safety. A total of 1,300 patients were randomly assigned to the darolutamide plus ADT plus docetaxel vs placebo plus ADT plus docetaxel. Results show the primary endpoint of the study was met with a significant improvement in overall survival and a 32% reduction in risk of death for patients on the triplet therapy with thalidomide plus ADT plus docetaxel. While this study offers an additional excellent option for our patients with metastatic castration sensitive prostate cancer, in an older patient population [the] use of docetaxel may be a significant limitation to this combination. In addition, this study did not answer the question [of] if adding docetaxel to ADT plus a novel hormonal therapy backbone will also improve survival with the advent of multiple doublets and triplet combinations. In the recent years, it is very important to find biomarkers which may predict response to these treatments and personalized therapy. Dr. Jason Efstathiou: Well, Neeraj, it certainly is a mic drop moment. Isn't it? When you can announce that the New England Journal of Medicine has just released the publication of your ARASENS trial, as you're presenting it at ASCO GU don't you think (DOI: 10.1056/NEJMoa2119115)? Dr. Neeraj Agarwal: Indeed, I think this is one of the most exciting ASCO GU meetings I've seen ever from GU ASCO. This is not an exaggeration. Dr. Jason Efstathiou: I totally agree. It was a phenomenal meeting and a very dynamic rich prostate day. Dr. Neeraj Agarwal: So, let's move on to the bladder cancer. Jason, what are your key takeaways from the studies of bladder cancer presented in this meet? Dr. Jason Efstathiou: Thanks, Neeraj. Yeah, the sessions on urothelial cancer were phenomenal and there were great sessions on novel therapies, such as antibody drug conjugates in advanced urothelial cancer and management of toxicities. There were abstracts such as [Abstract] 440 suggesting that neoadjuvant gemcitabine and cisplatin produced a favorable pathologic response rate and was well tolerated in patients with high grade upper tract urothelial carcinoma, and thus should be potentially deemed a new standard. Abstract 442 was a phase 2 trial that suggested that maintenance treatment with niraparib plus best supportive care did not improve outcomes compared to best supportive care alone, in patients with advanced urothelial carcinoma that did not progress after first-line chemotherapy. There was Abstract 435, which was an earlier face study suggesting that neoadjuvant treatment with enfortumab demonstrated promising activity among patients who are cisplatin ineligible with muscle invasive bladder cancer. And then there was a lot of focus in the meeting on trimodality therapy and optimizing bladder preservation. Dr. Alexandre R. Zlotta presented Abstract 433, which was a large multi-institutional match comparison of radical cystectomy to trimodality therapy for patients with muscle-invasive bladder cancer. And it suggested equivalent oncologic outcomes for select patients, and that trimodality therapy should be offered as an effective alternative for these patients. So Neeraj, moving on to kidney cancer, what were your key takeaways from these studies on kidney cancer presented in this meeting? Dr. Neeraj Agarwal: Yes, Jason, thank you. There were exciting results presented from multiple studies in kidney cancer as well. For example, Abstract 290 presented by Dr. Toni K. Choueiri from the Dana-Farber Cancer Institute on the 30-month follow-up of the KEYNOTE-564, which showed continued and strong disease-free survival benefit with adjuvant pembrolizumab in the context of localized or completely dissected renal cell carcinoma. I would like to highlight that highest benefit was seen in those patients who had oligometastatic disease, who on different surgery to remove those metastatic foresight and then were randomly assigned to receive pembrolizumab vs placebo in this trial. Abstract 291, presented by Dr. Matthew Zibelman from Fox Chase Cancer Center, showed the combination of axitinib with nivolumab was associated with close to 70% objective responses. Abstract 300 on kidney cancer on more than 1,000 patients—and on the International Metastatic Renal Cell Carcinoma Consortium, or IMDC Consortium—show that in the context of first-line immunotherapy regimens, presence of lung metastasis, CT nephrectomy and better MDC risk scores correlated with improved objective responses on this novel immunotherapy regimens. Abstract 350 on the update of the cabozantinib nivolumab was a sunitinib trial in metastatic renal cell carcinoma in the first-line setting. And it showed that the combination of cabozantinib nivolumab continues to be associated with an improved survival with the 30% reduction risk of death, even after this longer follow up—approximately 3 years. So, indeed, multiple abstracts on kidney cancer with real impact on how we practice medicine. So, Jason, let me switch gears here and talk about the education session. For example, there was a compelling keynote addressed by Dr. Karen Knudsen, the CEO of the American Cancer Society, about disparities in GU cancers in the United States. Are there any key messages that you would like to highlight briefly before we wrap up the podcast today? Dr. Jason Efstathiou: Thanks, Neeraj. Absolutely. The educational sessions were phenomenal. There was a must-see session, by the way, on management of rare variants in GU cancers. They made management of nuanced, rare variants and rare situations, very practical. And then there was an exciting prostate focus session called “Regulating the Wild West: PET-Based Imaging in Trials and the Clinic.” This session was planned with representatives from the U.S. Food and Drug Administration as we have done for the past 3 years. But this year it looked at how often PET based imaging affects clinical decision making and prostate cancer and how the integration of novel molecular based imaging like PET informs clinical trial design and endpoints, including regulatory considerations. And yes, of course, as you noted this year's program also focused on identifying and addressing disparities in cancer care and research with sessions each day, focused on this topic (Abstract 225, 446, 472, and 26). There were great oral presentations and there was a phenomenal Virtual Poster Walk with Dr. Ahmedin Jemal from the American Cancer Society. He, by the way, is an author that we have all quoted. So, please check that out. But we were thrilled, absolutely thrilled to have Dr. Karen Knudsen, the CEO of the American Cancer Society (ACS) as our keynote speaker to address this important topic in her phenomenal and frankly, inspiring talk called “A Path Forward: Addressing Disparities in Genitourinary Cancers.” This talk was especially poignant because as you know, there is a new and robust collaboration between ASCO and the ACS that was announced earlier this month on February 1, regarding equity, diversity, and inclusion in cancer care. ASCO's work aims to address all of the important differences that can impact access to cancer care and outcomes, including age, gender, race, sexual orientation, and geography, both in the U.S. and internationally. ASCO has clearly aligned its equity, diversity, and inclusion (EDI) goals within the mission pillars of research, education, and quality. Dr. Neeraj Agarwal: Thank you, Jason, for sharing your insights with us today. It is really an exciting time in GU oncology. Thank you. Dr. Jason Efstathiou: Thank You, Neeraj. I totally agree. Dr. Neeraj Agarwal: And thank you to our listeners for joining us today. You will find links to the abstracts discussed today on the transcript of this episode. Finally, if you like what you're hearing on the ASCO Daily News podcast, please take a moment to rate, review and subscribe wherever you get your podcast. Thank you so much. Disclosures: Dr. Neeraj Agarwal: Consulting or Advisory Role: Pfizer, Medivation/Astellas, Bristol-Myers Squibb, AstraZeneca, Nektar, Lilly, Bayer, Pharmacyclics, Foundation Medicine, Astellas Pharma, Lilly, Exelixis, AstraZeneca, Merck, Novartis, lily, Eisai, Seattle Genetics, EMD Serono, Janssen Oncology, AVEO, Calithera Biosciences, MEI Pharma, Genentech, Astellas Pharma, Foundation Medicine, and Gilead Sciences Research Funding (Institution): Bayer, Bristol-Myers Squibb, Takeda, Pfizer, Exelixis, Amgen, AstraZeneca, Calithera Biosciences, Celldex, Eisai, Genentech, Immunomedics, Janssen, Merck, Lilly, Nektar, ORIC Pharmaceuticals, ORIC Pharmaceuticals, crispr therapeutics, and Arvinas Dr. Jason Efstathiou: Consulting or Advisory Role: Blue Earth Diagnostics, AstraZeneca, Boston Scientific, Roivant Pharma, Merck, and Myovant Sciences Disclaimer: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guests' statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.
This week saw the opening of another multi-centre randomised trial of PSMA PET/CT in Australia. And it's a cracker! PRIMARY 2 follows on from the success of the PRIMARY trial published in European Urology recently (see links below). It is aimed at men with some clinical suspicion of prostate cancer, but no definite lesion on MRI (PIRADS 2/3). Is it ok to just to monitor these men (a la PRECISION)? Many will still undergo prostate biopsy if there is a high clinical suspicion (such as high PSA density, palpable lesion, strong family history), but could PSMA play a role in reducing the number of men undergoing biopsy, and provide a target in some cases? We are joined by trial co-PIs Professor Louise Emmett and Professor Michael Hofman, Nuclear Medicine Fellow Dr James Buteau and Urology lead A/Professor Daniel Moon, to discuss the innovative trial design. It will recruit 600 men from multiple sites across Australia. We're excited about this one! Plus a new segment! Urology Registrar Dr Aoife McVey is dropping in to tell us "what caught my eye on twitter" this week. Welcome Aoife!And PROStic nurse consultant Liz Medhurst gives a plug for the upcoming ProsTIC Preceptorship. Regular co-host Dr Renu Eapen is at ASCO GU so Daniel Moon kindly stepped in to help Declan Murphy todayAlso posted on YouTube Links:PRIMARY trial European Urology 2021 PRIMARY 1 podcastProsTIC PreceptorshipAoife's favourite tweet this week
Guest host Dr. Neeraj Agarwal, editor-in-chief of ASCO Daily News and director of the Genitourinary Cancers Program at the University of Utah Huntsman Cancer Institute, interviews Dr. Oliver Sartor, medical director of the Tulane Cancer Center in New Orleans, on the practice-changing VISION trial and its impact on the current treatment paradigm for mCRPC. Transcript ASCO Daily News: Welcome to the ASCO Daily News Podcast. Our topic today is the practice-changing VISION trial, a phase III trial of radioligand therapy in patients with metastatic castration-resistant prostate cancer. Our guest host, Dr. Neeraj Agarwal, the editor-in-chief of the ASCO Daily News and director of the Genitourinary Cancers Program at the University of Utah's Huntsman Cancer Institute, will speak with one of the trial's investigators, Dr. Oliver Sartor, the medical director of the Tulane Cancer Center and Laborde Professor for Cancer Research. Their full disclosures are available on the transcript of this episode, and disclosures relating to all episodes of the Daily News Podcast are available on our transcripts at asco.org/podcasts. Dr. Neeraj Agarwal: Hi, my name is Dr. Neeraj Agarwal. I am with Dr. Oliver Sartor. Today, we are going to discuss one of the practice-changing trials in the context of metastatic castration-resistant prostate cancer. Welcome to the ASCO Daily News Podcast, Dr. Sartor. Thanks for taking the time to be with us today. Dr. Oliver Sartor: Thank you, Neeraj. A pleasure to be here. Dr. Neeraj Agarwal: You recently published the primary results of the phase III VISION trial, which tested the efficacy of a novel radioligand therapy, Lutetium-177-PSMA-617, in men with metastatic castrate-resistant prostate cancer. Could you please tell us more about this compound and why you did this study? Dr. Oliver Sartor: So I'll start off with the compound itself. Radioligand therapy is a therapy that has a little warhead, and that warhead in this case is Lutetium-177. But it's guided by binding to PSMA. Now, PSMA is prostate-specific membrane antigen, and many of us are familiar with it, but some may not be. So PSMA is a protein expressed on the surface of most prostate cancer cells. Not all patients have it, but most do. And the ability of the PSMA Lutetium-177 to target the cancer was indicated in some preliminary studies, but they have not been to phase III. So the purpose of the phase III VISION trial was really to design a definitive study to look at overall survival, in particular, to determine whether or not this agent was truly active. And the good news is, it is truly active. And in the VISION trial, we were able to not only extend life with an overall survival benefit, haz ratio 0.62, but there was also a time-to-progression image-based radiographic progression-free survival. It was also much in favor of the PSMA Lutetium with a haz ratio of 0.4. So whether or not you look at time to cancer progression or whether or not you look at overall survival, this is an effective therapy. It, of course, does have some adverse side effects. We can talk more about that, but it's reasonably well tolerated. And I do anticipate that there'll be an FDA approval as a consequence of these pivotal findings. Dr. Neeraj Agarwal: These are wonderful results and news for our patients. Please tell me how it will affect the current treatment paradigm of our patients with mCRPC. As we know, you selected patients who had disease progression on chemotherapy with taxanes and novel hormonal therapy. But real-world studies, many of which were published by you, have shown that docetaxel is received by a minority of patients with metastatic prostate cancer. So how do you envision treating your patients who do not want to be treated with chemotherapy as many of my patients do? How will you apply Lutetium-177 in their treatment? Dr. Oliver Sartor: Well, Neeraj, I think that we're going to be restricted in accordance with the label that the FDA provides. And I fully expect that the label will include a progression after treatment with docetaxel or at least one taxane-based therapy because that's the way the VISION trial was constructed. Now, you're raising a very critical point, and that is, what about the individuals that do not want to receive or are ineligible to receive a chemotherapy such as docetaxel? And for those individuals, we now have a new trial called PSMA4, and that trial is going to be testing the Lutetium-177-PSMA-617 in the context of chemotherapy-naive patients. So I think we're going to have to wait until we have more results, more clinical trials completed, prior to the application of PSMA-617 into the more general population of chemotherapy-naive patients. But those clinical trials are now underway. Dr. Neeraj Agarwal: That's great. So, Oliver, in the VISION trial, you did mandate a diagnostic PSMA PET scan, and patients who were positive on the diagnostic PSMA PET scan were deemed to be eligible for enrollment on the VISION trial. Do you expect FDA to include diagnostic PSMA scan for eligibility for treatment with the Lutetium-177 in the real-world setting? If it doesn't or if it does, how it is going to affect the treatment of our patients, that availability of treatment for our patients? Dr. Oliver Sartor: That's really a great question. And I do expect that PSMA PET imaging will be a criteria given that it was used for patient selection. Now, as it turned out, about 87% of the patients actually did qualify after getting a PSMA PET scan. And given that that was part of the inclusion criteria, I anticipate that the FDA will also incorporate such imaging. Now, it does get to be a bit of an issue because it turns out that PSMA PET is just now coming into more widespread use. We did have, in May of this year, the approval by the FDA for the PSMA PET imaging agent and-- I shouldn't say "the"-- a PSMA PET imaging agent. Prior to that, in December of last year, there was both UCLA and UCSF approval by the FDA for yet another PSMA PET imaging agent. As we move forward, I anticipate that PET imaging is going to be more widely available. And of course, we don't have the approval as of yet today for the PSMA-617-Lutetium-177. And when we do get the anticipated approval, which likely will be in 2022, then I also anticipate that PSMA PET will be more widely available. Now, there are still issues with reimbursement for PSMA PET, and we've encountered those in our own practice. But that's a rapidly changing area, and we're working with the insurance companies in an effort to ensure that patients will get the imaging that they need. Dr. Neeraj Agarwal: Got it. And obviously, I asked this question because many of my community friends and colleagues have asked me this question. Before we talk about the side effects of Lutetium-177, would you have any message for our friends and colleagues in the community who are bracing themselves for treating their patients with the Lutetium-177, whether they should be proactive in establishing contacts and relationships with the nuclear medicine facilities and so on? Dr. Oliver Sartor: That's a great question, Neeraj, because I think you're raising a very important point. This is going to be the type of therapy that involves multidisciplinary care. We can see that there'll be diagnostic PET imaging as being a component of the study. There'll be the necessity of licensed physicians, typically either nuclear medicine or radiation oncology, to actually administer the drug. And then, quite frankly, the medical oncologists or those urologists who are trained in advanced prostate cancer are going to need to manage the patient. This is a lot more than just getting an injection. Many of these patients are ill. They need to have symptom management. They need to manage their bone health. They need to manage their hormonal manipulations. They need management with regard to pain. So this is not just about giving an injection. And I encourage those people who are interested to involve multidisciplinary teams starting now. And I realize that the therapy is not available now, but you have to anticipate that it will be. And I think it will be a game changer of a therapy, and many patients are going to want it. So that means it's incumbent upon the physicians to be prepared, and that means multidisciplinary care. Dr. Neearj Agarwal: Excellent point. So basically, we should be ready. We should start establishing relationships with nuclear medicine facilities or radiation oncologists who are going to deliver Lutetium-177. Overall, when I was reading the New England Journal paper, the side effect profile seemed very reasonable. I did not see any red flags. To me, it sounded like a pretty well-tolerated drug. So what is your take on the side effects of Lutetium-177? Dr. Oliver Sartor: I think the side effects are quite manageable. One of the unique side effects is that of dry mouth and that's because the PSMA can actually be expressed in the salivary glands and that there is some potential for salivary gland binding in the PSMA-617-Lutetium. And that means that you can have damage to the salivary glands, and that means dry mouth. It turns out that a little over 40% of the patients actually did complain of a dry mouth, and that needs to be managed typically with fluid intake or various ways of mouth moisturizers. Fatigue is a potential issue. It was raised, as well as some bone marrow suppression. And if you look at the grade 3/4 toxicities, anemia was present a little more than 10% of the time. And that, of course, needs to be monitored. There is some potential collateral damage to the bone marrow. So these patients need to have their counts monitored. They need to have their symptoms assessed. And they need to be managed as they go through the process. It's not just about giving an injection, but clearly, the licensed individuals, including nuclear medicine and radiation oncology, need to be engaged, because without them, there is no injection. So this is a complex multidisciplinary care paradigm. And emphasizing the point, symptom management, yes; adverse event management, yes. But you have to deliver the drug, and that means multidisciplinary care. Dr. Neeraj Agarwal: Those are fantastic points. Thank you very much, Dr. Sartor, for taking time to be with us. And I'm really hoping that this podcast will be very enriching to our listeners. Thank you very much. Dr. Oliver Sartor: Thank you, Neeraj. Glad to be here. ASCO Daily News: You've been listening to Dr. Neeraj Agarwal of the Huntsman Cancer Institute and Dr. Oliver Sartor of the Tulane Cancer Center. Our listeners will find a link to the VISION study in the transcript of this episode. Thank you to our listeners for joining us today. If you enjoyed this episode, please take a moment to rate, review, and subscribe wherever you get your podcasts. Disclosures: Dr. Neeraj Agarwal Consulting or Advisory Role: Pfizer, Medivation/Astellas, Bristol-Myers Squibb, AstraZeneca, Nektar, Lilly, Bayer, Pharmacyclics, Foundation Medicine, Astellas Pharma, Exelixis, Merck, Novartis, Eisai, Seattle Genetics, EMD Serono, Janssen Oncology, AVEO, Calithera Biosciences, MEI Pharma, Genentech, Astellas Pharma, Foundation Medicine, and Gilead Sciences Research Funding (Inst.): Bayer Your Institution, Bristol-Myers Squibb, Takeda, Pfizer, Exelixis, Amgen, AstraZeneca, Calithera Biosciences, Celldex, Eisai, Genentech, Immunomedics, Janssen, Merck, Lilly, Nektar, ORIC Pharmaceuticals, crispr therapeutics, and Arvinas Disclosures: Dr. Oliver Sartor Stocks & Other Ownership Interests: Lilly, GlaxoSmithKline, Abbvie, Cardinal Health, United Health Group, PSMA Therapeutics, Clarity Pharmaceuticals, Noria Therapeutics, Inc., Clovis Consulting or Advisory Role: Bayer, Sanofi, AstraZeneca, Dendreon, Constellation Pharmaceuticals, Advanced Accelerator Applications, Pfizer, Bristol-Myers Squibb, Bavarian Nordic, EMD Serono, Astellas Pharma, Progenics, Blue Earth Diagnostics, Myovant, Myriad Genetics, Novartis, Clarify Pharmaceuticals, Fusion, Istopen Technologien Meunchen, Janssen, Noxopharm, Clovis, Noria Therapeutics, Point Biopharma, TeneoBio, Telix, Theragnostics Research Funding (Inst): Sotio, Janssen, Progenics, Bayer, Sanofi, Endocyte, Merck, Invitae, Constellation Pharmaceuticals, Advanced Accelerator Applications, Dendreon, AstraZeneca Expert Testimony: Sanofi Travel, Accommodations, Expenses: Bayer, Johnson & Johnson, Sanofi, AstraZeneca, Progenics Disclaimer: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Dr. Oliver Sartor on the VISION Trial and Improving Care for Patients With mCRPC ASCO Daily News: Welcome to the ASCO Daily News Podcast. Our topic today is the practice-changing VISION trial, a phase III trial of radioligand therapy in patients with metastatic castration-resistant prostate cancer. Our guest host, Dr. Neeraj Agarwal, the editor-in-chief of the ASCO Daily News and director of the Genitourinary Cancers Program at the University of Utah's Huntsman Cancer Institute, will speak with one of the trial's investigators, Dr. Oliver Sartor, the medical director of the Tulane Cancer Center and Laborde Professor for Cancer Research. Their full disclosures are available on the transcript of this episode, and disclosures relating to all episodes of the Daily News Podcast are available on our transcripts at asco.org/podcasts. Dr. Neeraj Agarwal: Hi, my name is Dr. Neeraj Agarwal. I am with Dr. Oliver Sartor. Today, we are going to discuss one of the practice-changing trials in the context of metastatic castration-resistant prostate cancer. Welcome to the ASCO Daily News Podcast, Dr. Sartor. Thanks for taking the time to be with us today. Dr. Oliver Sartor: Thank you, Neeraj. A pleasure to be here. Dr. Neeraj Agarwal: You recently published the primary results of the phase III VISION trial, which tested the efficacy of a novel radioligand therapy, Lutetium-177-PSMA-617, in men with metastatic castrate-resistant prostate cancer. Could you please tell us more about this compound and why you did this study? Dr. Oliver Sartor: So I'll start off with the compound itself. Radioligand therapy is a therapy that has a little warhead, and that warhead in this case is Lutetium-177. But it's guided by binding to PSMA. Now, PSMA is prostate-specific membrane antigen, and many of us are familiar with it, but some may not be. So PSMA is a protein expressed on the surface of most prostate cancer cells. Not all patients have it, but most do. And the ability of the PSMA Lutetium-177 to target the cancer was indicated in some preliminary studies, but they have not been to phase III. So the purpose of the phase III VISION trial was really to design a definitive study to look at overall survival, in particular, to determine whether or not this agent was truly active. And the good news is, it is truly active. And in the VISION trial, we were able to not only extend life with an overall survival benefit, haz ratio 0.62, but there was also a time-to-progression image-based radiographic progression-free survival. It was also much in favor of the PSMA Lutetium with a haz ratio of 0.4. So whether or not you look at time to cancer progression or whether or not you look at overall survival, this is an effective therapy. It, of course, does have some adverse side effects. We can talk more about that, but it's reasonably well tolerated. And I do anticipate that there'll be an FDA approval as a consequence of these pivotal findings. Dr. Neeraj Agarwal: These are wonderful results and news for our patients. Please tell me how it will affect the current treatment paradigm of our patients with mCRPC. As we know, you selected patients who had disease progression on chemotherapy with taxanes and novel hormonal therapy. But real-world studies, many of which were published by you, have shown that docetaxel is received by a minority of patients with metastatic prostate cancer. So how do you envision treating your patients who do not want to be treated with chemotherapy as many of my patients do? How will you apply Lutetium-177 in their treatment? Dr. Oliver Sartor: Well, Neeraj, I think that we're going to be restricted in accordance with the label that the FDA provides. And I fully expect that the label will include a progression after treatment with docetaxel or at least one taxane-based therapy because that's the way the VISION trial was constructed. Now, you're raising a very critical point, and that is, what about the individuals that do not want to receive or are ineligible to receive a chemotherapy such as docetaxel? And for those individuals, we now have a new trial called PSMA4, and that trial is going to be testing the Lutetium-177-PSMA-617 in the context of chemotherapy-naive patients. So I think we're going to have to wait until we have more results, more clinical trials completed, prior to the application of PSMA-617 into the more general population of chemotherapy-naive patients. But those clinical trials are now underway. Dr. Neeraj Agarwal: That's great. So, Oliver, in the VISION trial, you did mandate a diagnostic PSMA PET scan, and patients who were positive on the diagnostic PSMA PET scan were deemed to be eligible for enrollment on the VISION trial. Do you expect FDA to include diagnostic PSMA scan for eligibility for treatment with the Lutetium-177 in the real-world setting? If it doesn't or if it does, how it is going to affect the treatment of our patients, that availability of treatment for our patients? Dr. Oliver Sartor: That's really a great question. And I do expect that PSMA PET imaging will be a criteria given that it was used for patient selection. Now, as it turned out, about 87% of the patients actually did qualify after getting a PSMA PET scan. And given that that was part of the inclusion criteria, I anticipate that the FDA will also incorporate such imaging. Now, it does get to be a bit of an issue because it turns out that PSMA PET is just now coming into more widespread use. We did have, in May of this year, the approval by the FDA for the PSMA PET imaging agent and-- I shouldn't say "the"-- a PSMA PET imaging agent. Prior to that, in December of last year, there was both UCLA and UCSF approval by the FDA for yet another PSMA PET imaging agent. As we move forward, I anticipate that PET imaging is going to be more widely available. And of course, we don't have the approval as of yet today for the PSMA-617-Lutetium-177. And when we do get the anticipated approval, which likely will be in 2022, then I also anticipate that PSMA PET will be more widely available. Now, there are still issues with reimbursement for PSMA PET, and we've encountered those in our own practice. But that's a rapidly changing area, and we're working with the insurance companies in an effort to ensure that patients will get the imaging that they need. Dr. Neeraj Agarwal: Got it. And obviously, I asked this question because many of my community friends and colleagues have asked me this question. Before we talk about the side effects of Lutetium-177, would you have any message for our friends and colleagues in the community who are bracing themselves for treating their patients with the Lutetium-177, whether they should be proactive in establishing contacts and relationships with the nuclear medicine facilities and so on? Dr. Oliver Sartor: That's a great question, Neeraj, because I think you're raising a very important point. This is going to be the type of therapy that involves multidisciplinary care. We can see that there'll be diagnostic PET imaging as being a component of the study. There'll be the necessity of licensed physicians, typically either nuclear medicine or radiation oncology, to actually administer the drug. And then, quite frankly, the medical oncologists or those urologists who are trained in advanced prostate cancer are going to need to manage the patient. This is a lot more than just getting an injection. Many of these patients are ill. They need to have symptom management. They need to manage their bone health. They need to manage their hormonal manipulations. They need management with regard to pain. So this is not just about giving an injection. And I encourage those people who are interested to involve multidisciplinary teams starting now. And I realize that the therapy is not available now, but you have to anticipate that it will be. And I think it will be a game changer of a therapy, and many patients are going to want it. So that means it's incumbent upon the physicians to be prepared, and that means multidisciplinary care. Dr. Neearj Agarwal: Excellent point. So basically, we should be ready. We should start establishing relationships with nuclear medicine facilities or radiation oncologists who are going to deliver Lutetium-177. Overall, when I was reading the New England Journal paper, the side effect profile seemed very reasonable. I did not see any red flags. To me, it sounded like a pretty well-tolerated drug. So what is your take on the side effects of Lutetium-177? Dr. Oliver Sartor: I think the side effects are quite manageable. One of the unique side effects is that of dry mouth and that's because the PSMA can actually be expressed in the salivary glands and that there is some potential for salivary gland binding in the PSMA-617-Lutetium. And that means that you can have damage to the salivary glands, and that means dry mouth. It turns out that a little over 40% of the patients actually did complain of a dry mouth, and that needs to be managed typically with fluid intake or various ways of mouth moisturizers. Fatigue is a potential issue. It was raised, as well as some bone marrow suppression. And if you look at the grade 3/4 toxicities, anemia was present a little more than 10% of the time. And that, of course, needs to be monitored. There is some potential collateral damage to the bone marrow. So these patients need to have their counts monitored. They need to have their symptoms assessed. And they need to be managed as they go through the process. It's not just about giving an injection, but clearly, the licensed individuals, including nuclear medicine and radiation oncology, need to be engaged, because without them, there is no injection. So this is a complex multidisciplinary care paradigm. And emphasizing the point, symptom management, yes; adverse event management, yes. But you have to deliver the drug, and that means multidisciplinary care. Dr. Neeraj Agarwal: Those are fantastic points. Thank you very much, Dr. Sartor, for taking time to be with us. And I'm really hoping that this podcast will be very enriching to our listeners. Thank you very much. Dr. Oliver Sartor: Thank you, Neeraj. Glad to be here. ASCO Daily News: You've been listening to Dr. Neeraj Agarwal of the Huntsman Cancer Institute and Dr. Oliver Sartor of the Tulane Cancer Center. Our listeners will find a link to the VISION study in the transcript of this episode. Thank you to our listeners for joining us today. If you enjoyed this episode, please take a moment to rate, review, and subscribe wherever you get your podcasts. Disclosures: Dr. Neeraj Agarwal Consulting or Advisory Role: Pfizer, Medivation/Astellas, Bristol-Myers Squibb, AstraZeneca, Nektar, Lilly, Bayer, Pharmacyclics, Foundation Medicine, Astellas Pharma, Exelixis, Merck, Novartis, Eisai, Seattle Genetics, EMD Serono, Janssen Oncology, AVEO, Calithera Biosciences, MEI Pharma, Genentech, Astellas Pharma, Foundation Medicine, and Gilead Sciences Research Funding (Inst.): Bayer Your Institution, Bristol-Myers Squibb, Takeda, Pfizer, Exelixis, Amgen, AstraZeneca, Calithera Biosciences, Celldex, Eisai, Genentech, Immunomedics, Janssen, Merck, Lilly, Nektar, ORIC Pharmaceuticals, crispr therapeutics, and Arvinas Disclosures: Dr. Oliver Sartor Stocks & Other Ownership Interests: Lilly, GlaxoSmithKline, Abbvie, Cardinal Health, United Health Group, PSMA Therapeutics, Clarity Pharmaceuticals, Noria Therapeutics, Inc., Clovis Consulting or Advisory Role: Bayer, Sanofi, AstraZeneca, Dendreon, Constellation Pharmaceuticals, Advanced Accelerator Applications, Pfizer, Bristol-Myers Squibb, Bavarian Nordic, EMD Serono, Astellas Pharma, Progenics, Blue Earth Diagnostics, Myovant, Myriad Genetics, Novartis, Clarify Pharmaceuticals, Fusion, Istopen Technologien Meunchen, Janssen, Noxopharm, Clovis, Noria Therapeutics, Point Biopharma, TeneoBio, Telix, Theragnostics Research Funding (Inst): Sotio, Janssen, Progenics, Bayer, Sanofi, Endocyte, Merck, Invitae, Constellation Pharmaceuticals, Advanced Accelerator Applications, Dendreon, AstraZeneca Expert Testimony: Sanofi Travel, Accommodations, Expenses: Bayer, Johnson & Johnson, Sanofi, AstraZeneca, Progenics Disclaimer: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Dr. Oliver Sartor on the VISION Trial and Improving Care for Patients With mCRPC ASCO Daily News: Welcome to the ASCO Daily News Podcast. Our topic today is the practice-changing VISION trial, a phase III trial of radioligand therapy in patients with metastatic castration-resistant prostate cancer. Our guest host, Dr. Neeraj Agarwal, the editor-in-chief of the ASCO Daily News and director of the Genitourinary Cancers Program at the University of Utah's Huntsman Cancer Institute, will speak with one of the trial's investigators, Dr. Oliver Sartor, the medical director of the Tulane Cancer Center and Laborde Professor for Cancer Research. Their full disclosures are available on the transcript of this episode, and disclosures relating to all episodes of the Daily News Podcast are available on our transcripts at asco.org/podcasts. Dr. Neeraj Agarwal: Hi, my name is Dr. Neeraj Agarwal. I am with Dr. Oliver Sartor. Today, we are going to discuss one of the practice-changing trials in the context of metastatic castration-resistant prostate cancer. Welcome to the ASCO Daily News Podcast, Dr. Sartor. Thanks for taking the time to be with us today. Dr. Oliver Sartor: Thank you, Neeraj. A pleasure to be here. Dr. Neeraj Agarwal: You recently published the primary results of the phase III VISION trial, which tested the efficacy of a novel radioligand therapy, Lutetium-177-PSMA-617, in men with metastatic castrate-resistant prostate cancer. Could you please tell us more about this compound and why you did this study? Dr. Oliver Sartor: So I'll start off with the compound itself. Radioligand therapy is a therapy that has a little warhead, and that warhead in this case is Lutetium-177. But it's guided by binding to PSMA. Now, PSMA is prostate-specific membrane antigen, and many of us are familiar with it, but some may not be. So PSMA is a protein expressed on the surface of most prostate cancer cells. Not all patients have it, but most do. And the ability of the PSMA Lutetium-177 to target the cancer was indicated in some preliminary studies, but they have not been to phase III. So the purpose of the phase III VISION trial was really to design a definitive study to look at overall survival, in particular, to determine whether or not this agent was truly active. And the good news is, it is truly active. And in the VISION trial, we were able to not only extend life with an overall survival benefit, haz ratio 0.62, but there was also a time-to-progression image-based radiographic progression-free survival. It was also much in favor of the PSMA Lutetium with a haz ratio of 0.4. So whether or not you look at time to cancer progression or whether or not you look at overall survival, this is an effective therapy. It, of course, does have some adverse side effects. We can talk more about that, but it's reasonably well tolerated. And I do anticipate that there'll be an FDA approval as a consequence of these pivotal findings. Dr. Neeraj Agarwal: These are wonderful results and news for our patients. Please tell me how it will affect the current treatment paradigm of our patients with mCRPC. As we know, you selected patients who had disease progression on chemotherapy with taxanes and novel hormonal therapy. But real-world studies, many of which were published by you, have shown that docetaxel is received by a minority of patients with metastatic prostate cancer. So how do you envision treating your patients who do not want to be treated with chemotherapy as many of my patients do? How will you apply Lutetium-177 in their treatment? Dr. Oliver Sartor: Well, Neeraj, I think that we're going to be restricted in accordance with the label that the FDA provides. And I fully expect that the label will include a progression after treatment with docetaxel or at least one taxane-based therapy because that's the way the VISION trial was constructed. Now, you're raising a very critical point, and that is, what about the individuals that do not want to receive or are ineligible to receive a chemotherapy such as docetaxel? And for those individuals, we now have a new trial called PSMA4, and that trial is going to be testing the Lutetium-177-PSMA-617 in the context of chemotherapy-naive patients. So I think we're going to have to wait until we have more results, more clinical trials completed, prior to the application of PSMA-617 into the more general population of chemotherapy-naive patients. But those clinical trials are now underway. Dr. Neeraj Agarwal: That's great. So, Oliver, in the VISION trial, you did mandate a diagnostic PSMA PET scan, and patients who were positive on the diagnostic PSMA PET scan were deemed to be eligible for enrollment on the VISION trial. Do you expect FDA to include diagnostic PSMA scan for eligibility for treatment with the Lutetium-177 in the real-world setting? If it doesn't or if it does, how it is going to affect the treatment of our patients, that availability of treatment for our patients? Dr. Oliver Sartor: That's really a great question. And I do expect that PSMA PET imaging will be a criteria given that it was used for patient selection. Now, as it turned out, about 87% of the patients actually did qualify after getting a PSMA PET scan. And given that that was part of the inclusion criteria, I anticipate that the FDA will also incorporate such imaging. Now, it does get to be a bit of an issue because it turns out that PSMA PET is just now coming into more widespread use. We did have, in May of this year, the approval by the FDA for the PSMA PET imaging agent and-- I shouldn't say "the"-- a PSMA PET imaging agent. Prior to that, in December of last year, there was both UCLA and UCSF approval by the FDA for yet another PSMA PET imaging agent. As we move forward, I anticipate that PET imaging is going to be more widely available. And of course, we don't have the approval as of yet today for the PSMA-617-Lutetium-177. And when we do get the anticipated approval, which likely will be in 2022, then I also anticipate that PSMA PET will be more widely available. Now, there are still issues with reimbursement for PSMA PET, and we've encountered those in our own practice. But that's a rapidly changing area, and we're working with the insurance companies in an effort to ensure that patients will get the imaging that they need. Dr. Neeraj Agarwal: Got it. And obviously, I asked this question because many of my community friends and colleagues have asked me this question. Before we talk about the side effects of Lutetium-177, would you have any message for our friends and colleagues in the community who are bracing themselves for treating their patients with the Lutetium-177, whether they should be proactive in establishing contacts and relationships with the nuclear medicine facilities and so on? Dr. Oliver Sartor: That's a great question, Neeraj, because I think you're raising a very important point. This is going to be the type of therapy that involves multidisciplinary care. We can see that there'll be diagnostic PET imaging as being a component of the study. There'll be the necessity of licensed physicians, typically either nuclear medicine or radiation oncology, to actually administer the drug. And then, quite frankly, the medical oncologists or those urologists who are trained in advanced prostate cancer are going to need to manage the patient. This is a lot more than just getting an injection. Many of these patients are ill. They need to have symptom management. They need to manage their bone health. They need to manage their hormonal manipulations. They need management with regard to pain. So this is not just about giving an injection. And I encourage those people who are interested to involve multidisciplinary teams starting now. And I realize that the therapy is not available now, but you have to anticipate that it will be. And I think it will be a game changer of a therapy, and many patients are going to want it. So that means it's incumbent upon the physicians to be prepared, and that means multidisciplinary care. Dr. Neearj Agarwal: Excellent point. So basically, we should be ready. We should start establishing relationships with nuclear medicine facilities or radiation oncologists who are going to deliver Lutetium-177. Overall, when I was reading the New England Journal paper, the side effect profile seemed very reasonable. I did not see any red flags. To me, it sounded like a pretty well-tolerated drug. So what is your take on the side effects of Lutetium-177? Dr. Oliver Sartor: I think the side effects are quite manageable. One of the unique side effects is that of dry mouth and that's because the PSMA can actually be expressed in the salivary glands and that there is some potential for salivary gland binding in the PSMA-617-Lutetium. And that means that you can have damage to the salivary glands, and that means dry mouth. It turns out that a little over 40% of the patients actually did complain of a dry mouth, and that needs to be managed typically with fluid intake or various ways of mouth moisturizers. Fatigue is a potential issue. It was raised, as well as some bone marrow suppression. And if you look at the grade 3/4 toxicities, anemia was present a little more than 10% of the time. And that, of course, needs to be monitored. There is some potential collateral damage to the bone marrow. So these patients need to have their counts monitored. They need to have their symptoms assessed. And they need to be managed as they go through the process. It's not just about giving an injection, but clearly, the licensed individuals, including nuclear medicine and radiation oncology, need to be engaged, because without them, there is no injection. So this is a complex multidisciplinary care paradigm. And emphasizing the point, symptom management, yes; adverse event management, yes. But you have to deliver the drug, and that means multidisciplinary care. Dr. Neeraj Agarwal: Those are fantastic points. Thank you very much, Dr. Sartor, for taking time to be with us. And I'm really hoping that this podcast will be very enriching to our listeners. Thank you very much. Dr. Oliver Sartor: Thank you, Neeraj. Glad to be here. ASCO Daily News: You've been listening to Dr. Neeraj Agarwal of the Huntsman Cancer Institute and Dr. Oliver Sartor of the Tulane Cancer Center. Our listeners will find a link to the VISION study in the transcript of this episode. Thank you to our listeners for joining us today. If you enjoyed this episode, please take a moment to rate, review, and subscribe wherever you get your podcasts. Disclosures: Dr. Neeraj Agarwal Consulting or Advisory Role: Pfizer, Medivation/Astellas, Bristol-Myers Squibb, AstraZeneca, Nektar, Lilly, Bayer, Pharmacyclics, Foundation Medicine, Astellas Pharma, Exelixis, Merck, Novartis, Eisai, Seattle Genetics, EMD Serono, Janssen Oncology, AVEO, Calithera Biosciences, MEI Pharma, Genentech, Astellas Pharma, Foundation Medicine, and Gilead Sciences Research Funding (Inst.): Bayer Your Institution, Bristol-Myers Squibb, Takeda, Pfizer, Exelixis, Amgen, AstraZeneca, Calithera Biosciences, Celldex, Eisai, Genentech, Immunomedics, Janssen, Merck, Lilly, Nektar, ORIC Pharmaceuticals, crispr therapeutics, and Arvinas Disclosures: Dr. Oliver Sartor Stocks & Other Ownership Interests: Lilly, GlaxoSmithKline, Abbvie, Cardinal Health, United Health Group, PSMA Therapeutics, Clarity Pharmaceuticals, Noria Therapeutics, Inc., Clovis Consulting or Advisory Role: Bayer, Sanofi, AstraZeneca, Dendreon, Constellation Pharmaceuticals, Advanced Accelerator Applications, Pfizer, Bristol-Myers Squibb, Bavarian Nordic, EMD Serono, Astellas Pharma, Progenics, Blue Earth Diagnostics, Myovant, Myriad Genetics, Novartis, Clarify Pharmaceuticals, Fusion, Istopen Technologien Meunchen, Janssen, Noxopharm, Clovis, Noria Therapeutics, Point Biopharma, TeneoBio, Telix, Theragnostics Research Funding (Inst): Sotio, Janssen, Progenics, Bayer, Sanofi, Endocyte, Merck, Invitae, Constellation Pharmaceuticals, Advanced Accelerator Applications, Dendreon, AstraZeneca Expert Testimony: Sanofi Travel, Accommodations, Expenses: Bayer, Johnson & Johnson, Sanofi, AstraZeneca, Progenics Disclaimer: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.
Das PSMA PET CT wird in der Diagnostik und Ausbreitungsdiagnostik sehr oft verwendet. Ob das auch gerechtfertigt ist, in welcher Frequenz und was dabei zu beachten ist erfahrt ihr in dieser Folge! Also hört rein und empfehlt den Podcast Euren Kollegen und Freunden. Und bitte schreibt und Euere Fragen auf unserem Instagram Kanal die_prostataspezialisten, wir beantworten diese in der kommenden Folge. Wenn Ihr mehr wissen wollt, schaut auf: www.die-Prostata-im-Fokus.de und www.der-Prostataspezialisten.com vorbei oder schreibt uns unter info@die-prostata-im-fokus.de Bernhard und Florian
Are GU Cast overly interested in PSMA imaging and theranostics??! Yep, afraid so! So no surprise that we're featuring this very interesting prospective trial published in European Urology this week. The objective is to evaluate the role of PSMA PET/CT prior to prostate biopsy ie in the early detection space. Can this augment mpMRI? Or replace it? Or is it all just madness due to profligate access to PSMA in Australia??!We are joined by PI Professor Louise Emmett, Nuclear Medicine Physician at St Vincent's in Sydney, to chat about the PRIMARY trial, and co-author Associate Professor Daniel Moon, Urologist at Peter MacCallum Cancer Centre who recruited close to 100 men into the trial (well done Dan!). And for a reality check to curb our enthusiasm, we are delighted to welcome back friend of the podcast, Professor Anwar Padhani, Oncologic Radiologist and MRI guru from Mt Vernon Cancer Centre and the Institute for Cancer Research in London. Co-hosts as ever, Professor Declan Murphy (also a co-author) and Dr Renu Eapen And yes we are cross-posting on YouTube so you can see how it all unfolds! Links:GU Cast on YouTube PRIMARY study in European Urology (paywall)Professor Emmet TwitterProfessor Padhani TwitterProfessor Padhani YoutubeAssociate Professor Moon Twitter
Better Edge : A Northwestern Medicine podcast for physicians
The FDA recently approved PSMA PET imaging agent 18F-DCFPyL (Pylarify) for identifying suspected metastasis or recurrence of prostate cancer. Northwestern Memorial Hospital is the first site in the Chicagoland market to perform prostate imaging using the this agent. What makes this approval so exciting, how will it change the field? How will it improve the diagnosis and treatment of prostate cancer patients?Edward Schaeffer MD, PhD, Ashley Ross MD, PhD and Hatice Savas MD discuss PET PSMA imaging for prostate cancer the recent FDA approval of Pylarify for prostate cancer detection.
Tobias Maurer berichtet, wie die PSMA PET von hinten das Feld aufrollt. Zunächst eingesetzt beim Rezidiv rückt sie jetzt in der Primärdiagnostik zunehmend in den Fokus.
The California Prostate Cancer Coalition (CPCC) and The Helen Family Diller Comprehensive Cancer Center present the 2021 Patient Conference on Prostate Cancer. This session: Tom Hope, MD, UCSF. Series: "Prostate Cancer Patient Conference" [Health and Medicine] [Show ID: 37268]
The California Prostate Cancer Coalition (CPCC) and The Helen Family Diller Comprehensive Cancer Center present the 2021 Patient Conference on Prostate Cancer. This session: Tom Hope, MD, UCSF. Series: "Prostate Cancer Patient Conference" [Health and Medicine] [Show ID: 37268]
The California Prostate Cancer Coalition (CPCC) and The Helen Family Diller Comprehensive Cancer Center present the 2021 Patient Conference on Prostate Cancer. This session: Tom Hope, MD, UCSF. Series: "Prostate Cancer Patient Conference" [Health and Medicine] [Show ID: 37268]
The California Prostate Cancer Coalition (CPCC) and The Helen Family Diller Comprehensive Cancer Center present the 2021 Patient Conference on Prostate Cancer. This session: Tom Hope, MD, UCSF. Series: "Prostate Cancer Patient Conference" [Health and Medicine] [Show ID: 37268]
The California Prostate Cancer Coalition (CPCC) and The Helen Family Diller Comprehensive Cancer Center present the 2021 Patient Conference on Prostate Cancer. This session: Tom Hope, MD, UCSF. Series: "Prostate Cancer Patient Conference" [Health and Medicine] [Show ID: 37268]
The California Prostate Cancer Coalition (CPCC) and The Helen Family Diller Comprehensive Cancer Center present the 2021 Patient Conference on Prostate Cancer. This session: Tom Hope, MD, UCSF. Series: "Prostate Cancer Patient Conference" [Health and Medicine] [Show ID: 37268]
The California Prostate Cancer Coalition (CPCC) and The Helen Family Diller Comprehensive Cancer Center present the 2021 Patient Conference on Prostate Cancer. This session: Tom Hope, MD, UCSF. Series: "Prostate Cancer Patient Conference" [Health and Medicine] [Show ID: 37268]
The California Prostate Cancer Coalition (CPCC) and The Helen Family Diller Comprehensive Cancer Center present the 2021 Patient Conference on Prostate Cancer. This session: Tom Hope, MD, UCSF. Series: "Prostate Cancer Patient Conference" [Health and Medicine] [Show ID: 37268]
This webinar focuses on expert speakers, Thomas Hope, MD and Matthew Cooperberg, MD, MPH providing insight on PSMA PET becoming standard clinical imaging. This webinar also discusses surgery versus radiation for treatment of High-Risk Prostate Cancer with talks and video review from Alice Semerjian, MD, Robert Dess, MD, and James Peabody, MD.
PROSTATE PROS Series Finale On the last episode of the PROSTATE PROS podcast, Dr. Scholz and Liz recap important themes and talk about what’s new in prostate cancer, including Lutetium-177 and Orgovyx. Dr. Scholz: [00:03] We’re guiding you to treatment success and avoiding prostate cancer pitfalls. I’m your host, Dr. Mark Scholz. Liz: [00:09] And I’m your cohost, Liz Graves. Dr. Scholz: [00:13] Welcome to the PROSTATE PROS podcast. Liz: [00:15] We have a bit of a sad announcement to make, as this will be the last episode of the PROSTATE PROS podcast. Dr. Scholz and I have really enjoyed working on this project and we’ve covered so many important topics surrounding prostate cancer and men’s health. So for this last episode, we’re going to recap some important themes and talk about some promising new therapies. So Dr. Scholz, on our very first episode, we talked about how important it is to find the right treatment team. This is something that’s come up again and again and again. What are some tips you have for newly diagnosed men trying to find their doctors? Dr. Scholz: [00:53] I think what’s confusing is how much of the responsibility falls on the shoulders of patients. The prostate industry is a very powerful multi-billion dollar industry, and there is a lot happening really fast. When patients are diagnosed, they’re not in a thoughtful perspective, they’re in an action mode, they’re frightened. It is hard to sort out who to listen to and who to stay away from. This process can be aided by family members, primary care doctors, oncologists, and of course, online resources and books. I try to provide some of that information in the book, The Key to Prostate Cancer, but the process, if it was easy, we could give you one simple answer. It is not a simple process. Liz: [01:46] One thing that we’ve talked about is to get a quarterback. So this is a doctor that isn’t the treating doctor necessarily, but it’s someone that will oversee the treatment and work with the other teams of doctors. This is something I hear you doing Dr. Scholz, you’re always talking to other doctors about patients and kind of networking with them to make sure that the patient is getting the best care, even when they’re not in our office. Dr. Scholz: [02:12] I think the issue that you’re relating to is that many of these physicians have a conflict of interest. You’re asking them, what should I do? But they’re a surgeon or they’re a radiation doctor. And as a medical oncologist, I’m neither of the above. This is somewhat uncommon, but you can recruit your urologist or your radiation doctor to help you by explaining at the outset that, “you, sir, will not be my treating doctor, but I definitely need your aid and your assistance in picking the right doctor.” Liz: [02:43] Now you may be thinking that you have cancer and you don’t have time to see all these people, but as we’ve mentioned, prostate cancer is slow growing. So really taking that time to find the right doctor for you is crucial. Dr. Scholz: [02:56] Just yesterday, I saw a very sophisticated new patient who was feeling the rush job, the sense that the clock is ticking, and he did have a Gleason 9. We consider that the High-Risk category of prostate cancer. But, the idea that you have to make a decision within days or weeks is never substantiated by the literature and the science. Patients can take several months to sort out what they want to do. This sort of careful thoughtful process pays off in the long-term with better results. Liz: [03:29] So patients really need to take it under their control. One of the things is to educate themselves. In the past couple of years, there’s been a huge shift towards imaging. So we’ve had the approval of the PSMA PET scan and using 3T MP MRIs and color Doppler to help men diagnose their prostate cancer and watch it. Dr. Scholz: [03:51] What Elizabeth is referring to is that if you don’t have a clear picture of where the cancer is and whether it’s spread outside the gland, what part of the gland it’s located in, it’s not feasible to tailor treatment to the specific needs of the individual. Some men are fortunate enough to have prostate cancers residing on one side of their gland. This opens the door to something called focal therapy, enabling men to undergo treatment with less risk of erectile dysfunction. There were a lot of things we could have covered in this last podcast and the reminder that quality imaging and not only MRI and PSMA PET scans, but scans done at centers of excellence that are read by experts are going to help men be light years ahead in their selection of treatment, because they’ll have a clear picture of what they’re really treating. Liz: [04:43] So we’ve actually gotten emails from people all across the country saying, you know, my doctor’s never heard of the PSMA PET scan or my doctor doesn’t do 3T imaging. So it is really important that you take the time to educate yourself and bring these questions to your doctors. Finding the right treatment team and doing your due diligence to make sure you’re choosing the right treatment is all important because of where the prostate is located. Treatment related side effects can have damaging effects on quality of life. Because prostate cancer is so slow growing, hopefully you’ll have a very long life, so it’s important that that can be lived to the best of your ability. Dr. Scholz: [05:25] That’s so, so important. And these functions, sexual, urinary functions are something that people face every day of their life. In the hustle bustle to get treatment quickly, the fact that if the treatment is not done in an ideal way, that men can be left with permanent issues unnecessarily, certainly if there was no other option, we would live with these negative consequences. But, in most cases now with skillful care, these things can be avoided. Liz: [05:58] Over the past two years, Dr. Scholz and I have covered all the treatment options from active surveillance to surgery, radiation chemotherapy. These episodes will still be available even after the podcast ends, you can go back and re-listen and keep sharing with friends and educating yourself. Dr. Scholz: [06:16] One thing about this information provided in the podcast is not only the idea of which treatment is best and what kind of things to look out for, but the step by step process, the thinking process, the procedures, and how you can come to get the right doctors and the right treatment is implicit in the whole podcast system that we have provided. So you can also just learn from the thought process that leads to successful outcomes. Liz: [06:49] While there are a lot of challenges that newly diagnosed patients face, patients with advanced prostate cancer also are missing out on some tools like Xgeva and Prolia. Dr. Scholz: [07:01] These medicines are to help compensate for men who have disease that’s spread to their bones or men who’ve been on hormone treatment and the calcium is leaching out, a process called osteoporosis. The number of times this is overlooked and people coming to us for second opinions is really quite surprising, as they are FDA approved to help compensate for these problems. So simple second opinions can be so valuable for men, even if they have advanced disease. Liz: [07:35] As we segue into what’s coming up and what’s new in prostate cancer, we wanted to quickly mention that there are a lot of new drugs and things being tested for FDA approval through clinical trials. Clinical trials are a great way to get access to these new medications, if you have a specialist on your team who is constantly looking out for these and keeping tabs on what’s coming up. Dr. Scholz: [08:03] Every new medicine or treatment goes through a process of being researched. Once it’s validated as a treatment, it gets FDA approved. And then after that, it becomes commercialized and broadly available across the country. The things that succeed through that process are very valuable. And we’ll be talking about a Lutetium-177 and a new pill called Orgovyx. These medicines have been available, but now are commercially available. If your physician is not staying abreast of all the new developments, men who could benefit from these treatments will be denied access simply through unawareness. Liz: [08:43] Lutetium-177 is something that we’ve talked about on past podcasts. And it’s not even FDA approved yet, but you’ve actually had some patients who have had it, is that correct? Dr. Scholz: [08:57] Lutetium-177 a was purchased by a Novartis pharmaceuticals for $2 billion prior to all the testing being completed because all the preliminary data looks so favorable recently, they released the code for the large clinical trial that was performed confirming that it does prolong survival. This is a medicine that was evaluated in men with very advanced prostate cancer who had already had chemotherapy who had been on other powerful hormone treatments and they’d stopped working. The man who got treated with Lutetium-177 lived longer, statistically significantly longer, than the men who got an alternative, placebo-type approach. This medicine is well tolerated. It can cause some dryness of people’s mouths. It can lower blood counts a little bit, but it’s a simple injection every six weeks. And it is a potent treatment for men with advanced disease. It may even be a useful treatment for men with earlier stage disease. This will probably be commercially available within a year. Liz: [10:05] To learn more about this medicine, we covered it in Episode 10, Don’t Reject Radiation. So you can go back and listen to that. At the end of 2020, there was a new FDA approval Orgovyx. This is an oral anti-androgen, so it works kind of like a Lupron, but instead of it being an injection, it’s just a daily pill. Dr. Scholz: [10:28] So how much do we really need a new pill? When if you could take an injection that lasts three to six months, and you don’t have to remember taking pills every day, but Orgovyx may have some other advantages when compared to head to head with Lupron and the other medicines like Lupron, such as Firmagon and Trelstar, Eligard, and Zoladex. These medicines all work by shutting down the production of testosterone in a man’s testicles. Orgovyx is interesting for two reasons. One is that the recovery of testosterone when treatment is stopped, seems to be much more predictable and consistent medicines like Lupron, and the others that I mentioned, can have a very protracted and prolonged effect even after they’re stopped, and it’s hard to predict when testosterone is going to return. Another thing that came out in Orgovyx trials was a lower incidence of cardiovascular complications. For years, I’ve made a strong argument that Lupron and other drugs do not cause cardiovascular problems directly, but indirectly in men who have a lot of weight gain, blood pressure goes up, blood sugars start to go out of control. Of course these things can lead to cardiovascular problems, but for some reason, in that randomized trial Orgovyx had a lower incidence of cardiovascular related issues. This is certainly an interesting and potential advantage for this medication. Liz: [11:56] Technology and medicine around prostate cancer is improving almost daily. And one of the things that’s really promising is immunotherapy. We talked about this on Episode 9, The Intelligence of Immunotherapy, and we cover all sorts of different things that will benefit men with prostate cancer, like KEYTRUDA and OPDIVO YERVOY. So if you’re interested in learning more about immunotherapy Episode 9 is a great place to start. Making this podcast has been such a rewarding experience for Dr. Scholz and I, and we really hope that it’s helped you on your prostate cancer journey. And we’ve left you with a little more education and knowledge and empowered you to take control of your prostate cancer diagnosis and spend time really learning about it and understanding, so you can have your medicine personalized to you. You can find the right doctors, seek second opinions, and then take everything you’ve learned to spread awareness about prostate cancer. Remember prostate cancer is a silent disease and it affects so many men and families and loved ones. This really needs to be something that people are comfortable talking about. So we hope our podcast has helped give you some points to talk about with your friends and family members and help them make those treatment decisions. Dr. Scholz: [13:26] So Kaili, my business manager and myself are very grateful to Liz for all the hard work she’s done in compiling these episodes and helping us reach the things that really count. It’s been quite a bit of work along the way, which has been a delight to participate in for me. Liz, can you just share a couple of sentences of where you think you’re going to be going with your own professional career as you’re moving on? Liz: [13:51] Yes. I am actually pursuing higher education to become a professional writer. I am looking forward to it, but I’m definitely sad that I won’t be working with you and bringing this podcast to everyone. I know I’ve had so much fun learning about prostate cancer and hopefully being able to help all of our listeners navigate this subject. Again, these episodes have been archived, so you can go back and listen to all twenty-four of them on podcast.prostateoncology.com, or Apple Podcasts, SoundCloud, wherever you like to listen. Another good tip is that the PCRI’s YouTube videos come out every week. These are awesome videos that talk all about prostate cancer. Dr. Scholz is a very frequent guest on there, so I would highly recommend you check that out. You can find them at youtube.com/thePCRI. Thank you for listening and supporting us.
We have some exciting news today! The FDA recently approved the first PSMA-targeted PET Gallium Scan for Prostate Cancer. In this episode, we will be talking to Dr. Rob Reiter, one of the primary investigators instrumental in helping to bring this new technology forward to get it approved for its initial use here in the USA. Dr. Reiter is the Bing Professor of Urology and Molecular Biology and Director of the Prostate Cancer Treatment and Research Program at the David Geffen School of Medicine at the University of California, Los Angeles. He is currently the principal investigator of UCLA's SPORE (Specialized Program in Research Excellence Program), a twelve-million-dollar research grant from the National Cancer Institute to develop new diagnostic and treatment options for men with prostate cancer. His clinical interests include robotic surgical management of prostate cancer and MRI and molecular imaging tools to manage this disease. He attended Stanford Medical School and completed his urologic training at Stanford and Baylor College of Medicine. He completed additional fellowship training in urologic cancer at the National Cancer Institute. Be sure to listen in today to learn more about this new technology. Disclaimer: The Prostate Health Podcast is for informational purposes only. Nothing in this podcast should be construed as medical advice. By listening to the podcast, no physician-patient relationship has been formed. For more information and counseling, you must contact your personal physician or urologist with questions about your unique situation. Show highlights: Dr. Reiter gives a brief overview of some of the imaging tests that have been used over the years for prostate cancer. Dr. Reiter explains why he thinks that MRI has revolutionized how we diagnose prostate cancer. Dr. Reiter explains what PSMA stands for. Dr. Reiter talks about the newly approved PSMA targeted PET Gallium Scan for Prostate Cancer. Dr. Reiter explains how the drug gets administered before the testing. Dr. Reiter describes the situations where the new scan has been approved to help men with prostate cancer. He also describes the advantages of the PSMA PET technology when compared with older imaging options. Dr. Reiter tells us which US locations have currently been approved to offer the PSMA PET scan. Dr. Reiter discusses whether the PSMA PET scan is covered currently by Medicare and private insurance companies. Dr. Reiter discusses the possibility of The PSMA PET scan supplanting the MRI or becoming an adjunct to it. Dr. Reiter talks about some potential future applications of the PSMA agent in addition to its current indications with initial staging and localization of recurrence. Make sure you don't miss listening to our bonus content! You can sign up to be included on our list here. Links and resources: Follow Dr. Pohlman on Twitter and Instagram - @gpohlmanmd Get your free What To Expect Guide (or find the link here, on our podcast website) Join our Facebook group Follow Dr. Pohlman on Twitter and Instagram Go to the Prostate Health Academy to sign up for the wait-list for our bonus video content. You can access Dr. Pohlman's free mini webinar, where he discusses his top three tips to promote men's prostate health, longevity, and quality of life here.
Big day today with the approval of Ga68-PSMA PET/CT by the US Food and Drugs Administration (FDA). The FDA have approved a combined academic application from the University of California San Francisco (UCSF) and the University of California Los Angeles (UCLA), and means that those two centres now have FDA approval to use PSMA PET/CT for staging newly-diagnosed prostate cancer, as well as those with suspected recurrence following previous treatment. Today we chat with the UCSF team behind the application, led by Dr Thomas Hope, Nuclear Medicine Physician and Radiologist, and his urology colleagues Dr Peter Carroll and Dr Matt Cooperberg. Fantastic discussion about what this means for access to PSMA PET/CT across the whole country; what it means for trial design; what other agents are on the horizon; and a steal peak from Dr Carroll about other research areas in PSMA he is exploring at UCSF. Regular hosts Professor Declan Murphy and Dr Renu Eapen are joined once again by Professor Michael Hofman, Nuclear Medicine Physician at Peter MacCallum Cancer Centre. LinksFDA news release on PSMA PET/CT UCSF UrologyUCSF Nuclear MedicineUCLA UrologyUCLA Nuclear Medicine
Thomas Hope is quizzed on the results of his study presented at ASCO20.
Mike Morris presents the findings in his prospective study.
Thanks to Dr Howard Soule and our friends at the Prostate Cancer Foundation in the USA, we are delighted to post this GU Cast special episode on PSMA PET/CT. PCF today hosted their first PCF Global Journal Club Webinar, focussing on PSMA PET/CT. Professor Michael Hofman presented an overview of the proPSMA trial recently published in the Lancet, with a lively panel discussion and questions from the global audience of almost 300 active participants. Join Howard, Michael, and special guests Prof Caroline Moore, Prof Jeremie Calais, Prof Scott Williams, Dr Kirsten Greene, and GU Cast host, Prof Declan Murphy, in this podcast of today's PCF Global Journal Club Webinar.
© 2020-2025 Ivy Podcast Discovery LLC
