Podcasts about psma

For serious PSMA theranostics enthusiasts!!! We bring you the ninth of our collaborative PSMA webinars over the past five years, in collaboration with our team at ProsTIC and at the Prostate Cancer Foundation in the US. A truly outstanding faculty presenting today including Misha Beltran, Marty Pomper, Ed Kwan and Louise Emmett.Co-hosted by Declan Murphy and Michael Hofman with a welcome from Howard Soule and Andrea Miyahira. Declan and Michael are joined in studio by Louise Kostos who helps field the many questions from the huge global audience who joined us live. Much better appreciated on our YouTube channel where you can see all the presentations 

Marie Curie's life work laid the foundations for theranostics. This week, we talk about Lutetium, a rare earth metal, and its role in Prostate Cancer. Lutetium-177 PSMA therapy is a radiation therapy that targets prostate cancer. It is used in the advanced, metastatic, and castrate-resistant space. Lutetium is bound to a protein called PSMA. PSMA is overexpressed in many prostate cancers and can be used to target these cancer cells via the membrane antigen.Studies discussed in the episode:UpFrontPSMAVISION trial (and a bit on TheraP)For more episodes, resources and blog posts, visit www.inquisitiveonc.comPlease find us on Twitter @InquisitiveOnc!If you want us to look at a specific trial or subject, email us at inquisitiveonc@gmail.comArt courtesy of Taryn SilverMusic courtesy of AlisiaBeats: https://pixabay.com/users/alisiabeats-39461785/Disclaimer: This podcast is for educational purposes only. If you are unwell, seek medical advice.Oncology for the Inquisitive Mind is recorded with the support of education grants from our foundation partners Pfizer, Gilead Pharmaceuticals and Merck Pharmaceuticals. Our partners have access to the episode at the same time you do and have no editorial control over the content. Hosted on Acast. See acast.com/privacy for more information.

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 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...

Elena Castro joins Tom and Brian on the day after Pluvicto approval pre-chemotherapy in the US to discuss the PSMA Fore data and application in clinical practice.

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

MILANO (ITALPRESS) - Al via un nuovo trattamento innovativo per la cura del carcinoma prostatico metastatico resistente alla castrazione. Si tratta della terapia con radioligandi Lutetium, per cui l'Agenzia Italiana del Farmaco ha approvato l'ammissione alla rimborsabilità. Dopo la pubblicazione in Gazzetta Ufficiale lo scorso 3 marzo, la nuova terapia sarà disponibile nelle singole regioni non appena saranno conclusi gli iter regionali. Questo traguardo rende accessibile ai pazienti affetti da carcinoma prostatico metastatico PSMA positivo la prima terapia con radioligandi, un'innovazione della medicina di precisione basata sulla teragnostica che unisce fase diagnostica e fase terapeutica in un approccio che consente di colpire in modo mirato le cellule tumorali, migliorando conseguentemente l'efficacia del trattamento e la tollerabilità per i pazienti.xm4/mgg/gtr

MILANO (ITALPRESS) - Al via un nuovo trattamento innovativo per la cura del carcinoma prostatico metastatico resistente alla castrazione. Si tratta della terapia con radioligandi Lutetium, per cui l'Agenzia Italiana del Farmaco ha approvato l'ammissione alla rimborsabilità. Dopo la pubblicazione in Gazzetta Ufficiale lo scorso 3 marzo, la nuova terapia sarà disponibile nelle singole regioni non appena saranno conclusi gli iter regionali. Questo traguardo rende accessibile ai pazienti affetti da carcinoma prostatico metastatico PSMA positivo la prima terapia con radioligandi, un'innovazione della medicina di precisione basata sulla teragnostica che unisce fase diagnostica e fase terapeutica in un approccio che consente di colpire in modo mirato le cellule tumorali, migliorando conseguentemente l'efficacia del trattamento e la tollerabilità per i pazienti.xm4/mgg/gtr

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:

Dr. Sue Yom, Editor in Chief, hosts guests Dr. Cristian Udovicich, a Fellow in Radiation Oncology at the University of Toronto's Sunnybrook Odette Cancer Centre, and Dr. Angela Jia, Assistant Professor and Assistant Residency Program Director at University Hospitals Cleveland Medical Center, who were the first and second authors of "Evolving Paradigms in Prostate Cancer: The Integral Role of Prostate-Specific Membrane Antigen Positron Emission Tomography/Computed Tomography in Primary Staging and Therapeutic Decision-Making." In addition, we review long-term SBRT results with Dr. Andrew Loblaw, Full Professor in the Department of Radiation Oncology and Institute of Health Policy, Management and Evaluation at Sunnybrook Health Science Center at the University of Toronto and supervising author of "Stereotactic Radiation Therapy for Localized Prostate Cancer: 10-Year Outcomes From Three Prospective Trials," and Dr. Constantinos Zamboglou, Deputy Medical Director at the German Oncology Center in Limassol, Cyprus and first author of an accompanying editorial, "Stereotactic Body Radiotherapy for Prostate Cancer is Getting Mature: 10-Year Outcomes From Three Prospective Trials."

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!

- Thưa quý vị và các bạn! Việc thực hiện Hiệp định về biện pháp quốc gia có cảng (PSMA) có ý nghĩa quyết định để tháo gỡ thẻ vàng của Châu Âu đối với nghề cá ở Việt Nam. Chúng ta thể hiện với cộng đồng quốc tế rằng Việt Nam là một thành viên, có cam kết chung với cộng đồng quốc tế trong phòng, chống khai thác IUU và phát triển nghề cá toàn cầu một cách bền vững và có trách nhiệm. Việc thực hiện PSMA góp phần tăng cường vị trí, vai trò của ngành thủy sản Việt Nam nói riêng và của Việt Nam nói chung trong quá trình tiến trình hội nhập kinh tế quốc tế và xây dựng, phát triển cái thương hiệu thủy sản Việt Nam. Việt Nam chính thức tham gia vào Hiệp định PSMA, qua 4 năm triển khai thực hiện, mặc dù đã đạt được một số thành công nhât định, tuy nhiên để việc triển khai thực hiện Hiệp định PSMA một cách có hiệu quả, vẫn còn đó một số khó khăn, trở ngại cần phải tháo gỡ. Đây là nội dung được bàn luận trong chương trình hôm nay. Khách mời của chương trình.-Bà Nguyễn Thị Trang Nhung, Trưởng phòng KHCN và Hợp tác quốc tế, Cục Kiểm ngư, Bộ NN&PTNT. --- Support this podcast: https://podcasters.spotify.com/pod/show/vov1sukien/support

- Thực thi Hiệp định về biện pháp quốc gia có cảng (PSMA) có ý nghĩa quyết định để tháo gỡ thẻ vàng của Ủy ban châu Âu đối với nghề cá ở Việt Nam; thể hiện cam kết chung với cộng đồng quốc tế trong phòng, chống khai thác hải sản bất hợp pháp, không báo cáo và không theo quy định (IUU), góp phần phát triển nghề cá toàn cầu một cách bền vững và có trách nhiệm. Việc thực thi Hiệp định cũng góp phần tăng cường vị trí, vai trò của ngành thủy sản Việt Nam trong tiến trình hội nhập kinh tế quốc tế và xây dựng, phát triển thương hiệu thủy sản.Sau 4 năm thực hiện, dù đạt một số kết quả nhất định nhưng vẫn còn đó những khó khăn, trở ngại cần phải tháo gỡ. Cùng bàn luận nội dung nà với khách mời là bà Nguyễn Thị Trang Nhung, Trưởng phòng Khoa học công nghệ và Hợp tác quốc tế, Cục Kiểm ngư, Bộ Nông nghiệp và Phát triển nông thôn. Chủ đề : PSMA, IUU --- Support this podcast: https://podcasters.spotify.com/pod/show/vov1sukien/support

- Thưa quý vị và các bạn! Việc thực hiện Hiệp định về biện pháp quốc gia có cảng (PSMA) có ý nghĩa quyết định để tháo gỡ thẻ vàng của Châu Âu đối với nghề cá ở Việt Nam. Chúng ta thể hiện với cộng đồng quốc tế rằng Việt Nam là một thành viên, có cam kết chung với cộng đồng quốc tế trong phòng, chống khai thác IUU và phát triển nghề cá toàn cầu một cách bền vững và có trách nhiệm. Việc thực hiện PSMA góp phần tăng cường vị trí, vai trò của ngành thủy sản Việt Nam nói riêng và của Việt Nam nói chung trong quá trình tiến trình hội nhập kinh tế quốc tế và xây dựng, phát triển cái thương hiệu thủy sản Việt Nam. Việt Nam chính thức tham gia vào Hiệp định PSMA, qua 4 năm triển khai thực hiện, mặc dù đã đạt được một số thành công nhât định, tuy nhiên để việc triển khai thực hiện Hiệp định PSMA một cách có hiệu quả, vẫn còn đó một số khó khăn, trở ngại cần phải tháo gỡ. Đây là nội dung được bàn luận trong chương trình hôm nay. Khách mời của chương trình:-Bà Nguyễn Thị Trang Nhung, Trưởng phòng KHCN và Hợp tác quốc tế, Cục Kiểm ngư, Bộ NN&PTNT- Ông Đặng Văn Long, Chi Cục Thú ý Vùng IV --- Support this podcast: https://podcasters.spotify.com/pod/show/vov1sukien/support

Part 2 Highlights from a GU Cast Live Event! Dr Kim Chi (Medical Oncologist, Vancouver) and Dr Carmen Mir (Urologist, Valencia) joined the PROSPECT meeting in Melbourne to discuss high-risk prostate cancer and mHSPC, along with many experts from around Australia. On the eve of the meeting over dinner, Declan Murphy led a GU Cast-themed panel discussion on five hot topics in prostate cancer, featuring snippets from GU Cast over the past few months.Part 2 today features controversies in PLND, the somewhat notorious ARPI switch control arm beloved of mCRPC trials, and teh importnt topic of de-escalation in advanced prostate cancer. Part 1 recently in your feeds included PSMA conundrums and triplet vs doublet therapy.Even better on our YouTube channelThis is a Themed Podcast supported by our Gold Partners, Johnson & Johnson, who also support the PROSPECT meeting. Special thanks to David Chen for help with videography

Highlights from a GU Cast Live Event! Dr Kim Chi (Medical Oncologist, Vancouver) and Dr Carmen Mir (Urologist, Valencia) joined the PROSPECT meeting in Melbourne to discuss high-risk prostate cancer and mHSPC, along with many experts from around Australia. On the eve of the meeting over dinner, Declan Murphy led a GU Cast-themed panel discussion on five hot topics in prostate cancer, featuring snippets from GU Cast over the past few months. Part 1 today features PSMA conundrums and triplet vs doublet therapy. Even better on our YouTube channel This is a Themed Podcast supported by our Gold Partners, Johnson & Johnson, who also support the PROSPECT meeting. Special thanks to David Chen for help with videography

Dr. Ashwin Singh Parihar speaks with Dr. Phillip Kuo, Dr. Andrew Armstrong, and Dr. Ken Herrmann about how 68Ga-PSMA-11 PET can predict response of metastatic prostate cancer following 177Lu-PSMA-617 therapy. The VISION Trial. Quantitative 68Ga-PSMA-11 PET and ClinicalOutcomes in Metastatic Castration-resistant ProstateCancer Following 177Lu-PSMA-617 (VISION Trial). Kuo and Morris et al. Radiology 2024; 312(2):e233460.  

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

In the first episode of this three-part series focused on the presentations and findings from the ESMO Congress 2024, our hosts focus on mCSPC prostate cancer treatment advancements, including lutetium PSMA, darolutamide and much more. 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.ca This podcast has been made possible through unrestricted financial support by Astellas, AstraZeneca, Bayer, Bristol Myers Squibb, Eisai, Ipsen, J&J Innovative Medicine, Merck, Novartis, Pfizer, TerSera.

Dr. Ashwin Singh Parihar discusses the role of multiparametric MRI and 18F-PSMA-1007 PET/CT for the detection of clinically significant prostate cancer with Dr. Bastiaan Privé. This episode is sponsored by Mayo Clinic. Multiparametric MRI and 18F-PSMA-1007 PET/CT for the Detection of Clinically Significant Prostate Cancer. Privé et al. Radiology 2024; 311(2):e231879.

Guest: Geoffrey B. Johnson, M.D., Ph.D. When looking at patients who suffer from prostate cancer who are receiving PSMA therapy, we can see on our images that the medication not only goes to their cancer, but it also goes to some other things in their body, including the salivary glands. To learn more about his recent study on salivary toxicity, join Dr. Geoffrey Johnson, Nuclear Medicine Specialist and Radiologist at the Mayo Clinic in Rochester, Minnesota.

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.

Welcome to another insightful episode of the Oncology Brothers podcast! In this episode, hosts Drs. Rahul and Rohit Gosain are joined by Dr. Toni Choueiri, a GU Medical Oncologist from Dana-Farber Cancer Institute, to discuss key abstracts from ASCO 2024. They delve into topics such as the impact of the EV302 study on metastatic bladder cancer, the potential role of ctDNA as a biomarker in bladder cancer, real-world data on metastatic RCC, and the PSMA-4 study in prostate cancer. The discussion covers patient-reported outcomes, treatment strategies, and the evolving landscape of oncology care. Tune in to gain valuable insights into the latest advancements in oncology and how they are shaping the standard of care for patients. Don't miss out on this engaging conversation with experts in the field. Subscribe to the Oncology Brothers podcast for more updates from the world of oncology. Website: http://www.oncbrothers.com/ Twitter: https://twitter.com/oncbrothers Contact us at info@oncbrothers.com

This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME information, and to apply for credit, please visit us at PeerView.com/QSV865. CME credit will be available until May 23, 2025.On Target: Understanding the Impact of PSMA for Diagnostic and Therapeutic Strategies in Prostate Cancer In support of improving patient care, PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported by educational grants from Blue Earth Diagnostics, Lantheus Medical Imaging, and Novartis Pharmaceuticals Corporation.Disclosure information is available at the beginning of the video presentation.

This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME information, and to apply for credit, please visit us at PeerView.com/QSV865. CME credit will be available until May 23, 2025.On Target: Understanding the Impact of PSMA for Diagnostic and Therapeutic Strategies in Prostate Cancer In support of improving patient care, PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported by educational grants from Blue Earth Diagnostics, Lantheus Medical Imaging, and Novartis Pharmaceuticals Corporation.Disclosure information is available at the beginning of the video presentation.

This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME information, and to apply for credit, please visit us at PeerView.com/QSV865. CME credit will be available until May 23, 2025.On Target: Understanding the Impact of PSMA for Diagnostic and Therapeutic Strategies in Prostate Cancer In support of improving patient care, PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported by educational grants from Blue Earth Diagnostics, Lantheus Medical Imaging, and Novartis Pharmaceuticals Corporation.Disclosure information is available at the beginning of the video presentation.

This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME information, and to apply for credit, please visit us at PeerView.com/QSV865. CME credit will be available until May 23, 2025.On Target: Understanding the Impact of PSMA for Diagnostic and Therapeutic Strategies in Prostate Cancer In support of improving patient care, PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported by educational grants from Blue Earth Diagnostics, Lantheus Medical Imaging, and Novartis Pharmaceuticals Corporation.Disclosure information is available at the beginning of the video presentation.

This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME information, and to apply for credit, please visit us at PeerView.com/QSV865. CME credit will be available until May 23, 2025.On Target: Understanding the Impact of PSMA for Diagnostic and Therapeutic Strategies in Prostate Cancer In support of improving patient care, PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported by educational grants from Blue Earth Diagnostics, Lantheus Medical Imaging, and Novartis Pharmaceuticals Corporation.Disclosure information is available at the beginning of the video presentation.

This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME information, and to apply for credit, please visit us at PeerView.com/QSV865. CME credit will be available until May 23, 2025.On Target: Understanding the Impact of PSMA for Diagnostic and Therapeutic Strategies in Prostate Cancer In support of improving patient care, PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported by educational grants from Blue Earth Diagnostics, Lantheus Medical Imaging, and Novartis Pharmaceuticals Corporation.Disclosure information is available at the beginning of the video presentation.

This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME information, and to apply for credit, please visit us at PeerView.com/QSV865. CME credit will be available until May 23, 2025.On Target: Understanding the Impact of PSMA for Diagnostic and Therapeutic Strategies in Prostate Cancer In support of improving patient care, PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported by educational grants from Blue Earth Diagnostics, Lantheus Medical Imaging, and Novartis Pharmaceuticals Corporation.Disclosure information is available at the beginning of the video presentation.

Check out this week's QuadCast as we highlight a better RT dosing schedule for vulvar cancer, metastasis directed therapy for nasopharyngeal cancer, PSMA targeted 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

Silke covers key aspects of the meeting, including surgery vs RT, genetic and somatic testing, PSMA imaging and 1st line triplet therapy.

The 2nd ProsTIC Preceptorship is one of the most intense fora for the discussion of PSMA theranostics anywhere in the world! A biennial meeting in Melbourne with many of the world's leading experts in the field. Not just superb practical advice about how to get your prostate cancer theranostics program to the next level, but some amazing discussions on where to next for theranostics in prostate cancer. Plus, watch out for the shenanigans at the conference dinner!Our Conference Highlights are supported by our friends at Bayer China.Even better on our YouTube channel 

Q&A episode 6 includes: * Diet tips for diabetic PCa guys * Lupron or alternatives * What is PSMA averse * If radiation worked how can it come back * Prostate App updates * Prostate night at the Royals   Watch more episodes and submit your questions at https://www.prostatenetwork.org/qa

The 2nd ProsTIC Preceptorship is one of the most intense fora for the discussion of PSMA theranostics anywhere in the world! A biennial meeting in Melbourne with many of the world's leading experts in the field. Not just superb practical advice about how to get your prostate cancer theranostics program to teh next level, but some amazing discussions on where to next for theranostics in prostate cancer. Plus, watch out for the shenanigans at the conference dinner! Our Conference Highlights are supported by our friends at Bayer China. Even better on our YouTube channel 

Tanya Dorff describes acapatamab, a prostate-specific membrane antigen (PSMA) CD3 bispecific engager.

In this episode, Dr. Edward Schaeffer, chair of urology at Feinberg School of Medicine, discusses precision medicine in prostate cancer with Dr. Aditya Bagrodia. First, Dr. Schaeffer introduces the importance of using a defined screening strategy for prostate cancer that includes analyzing a patient's genomic and germline risk. Then, he summarizes existing and new diagnostic tools for prostate cancer. Additionally, Dr. Schaeffer discusses genomic testing and PSMA testing and explains how he applies them to individual patient cases depending on their cancer stage and grade. Finally, the doctors highlight the ability of future tools, like PET PSMA scans, to advance precision medicine. --- EARN CME Reflect on how this Podcast applies to your day-to-day and earn free AMA PRA Category 1 CMEs: https://earnc.me/3XO8iL --- SHOW NOTES 00:00 - Introduction 10:32 - Precision Medicine and Prostate Cancer 16:17 - Screening and Diagnosis of Prostate Cancer 29:41 - Personalizing Surveillance and Disease Management 33:11 - The Role of Genomic Testing in Prostate Cancer 45:00 - The Use of PET PSMA Scans in Prostate Cancer Staging 48:08 - The Future of Precision Medicine in Prostate Cancer

For all you enthusiasts of PSMA theranostics, we bring you another one of our fabulous ProsTIC/Prostate Cancer Foundation Global Webinars with some of the best minds in the business. This is the eighth of our collaborative webinars over the past four years and the focus today is bringing lutetium PSMA earlier in prostate cancer.Two keynote lectures from Dr Oliver Sartor (Mayo Clinic) and Professor Louise Emmett (St Vincent's. Sydney)set the scene, focusing on brand-new data from the PSMAfore  and Enza-P trials. We have an Asia-Pacific focus with a superb range of multidisciplinary panellists from across the region.Co-Hosted by GU Cast's own Dr Renu Eapen with Professor Michael Hofman from ProsTIC/Peter MacCallum Cancer Centre. They are joined in studio by friends of the podcast Dr Louise Kostos and Dr James Buteau. Even better on our YouTube channel where you can see the presentations

Professor Mike Sathekge (Department of Nuclear Medicine, University of Pretoria, Pretoria, South Africa) discusses his Article entitled, ‘Actinium-225-PSMA radioligand therapy of metastatic castration-resistant prostate cancer (WARMTH Act): a multicentre retrospective study.'Read the full article:https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(23)00638-1/fulltext?dgcid=buzzsprout_icw_podcast_generic_lanoncContinue this conversation on social!Follow us today at...https://twitter.com/thelancet & https://Twitter.com/TheLancetOncolhttps://instagram.com/thelancetgrouphttps://facebook.com/thelancetmedicaljournalhttps://linkedIn.com/company/the-lancethttps://youtube.com/thelancettv

We made it to the end of another series. In our FINAL episode of the prostate cancer series, we turn our attention to metastatic castrate-resistant prostate cancer! We discuss treatment options, the data behind why we do what we do, and more targeted agents.Content: - Approach to metastatic castrate-resistant prostate cancer- Refresher on what it means to be castrate-resistant - Role of bisphosphate therapy and denosumab- Treatment options and data surrounding sequencing of agents - Other options for prostate cancer (radium-223 and lutetium-177-PSMA-617)- Role of PARP inhibitors in BRCA-mutated disease ** 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

You're listening to a podcast from Cancer.Net. This cancer information website is produced by the American Society of Clinical Oncology, known as ASCO, the voice of the world's oncology professionals. 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 this 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. Cancer research discussed in this podcast is ongoing, so data described here may change as research progresses. In this podcast, members of the Cancer.Net Editorial Board discuss the latest research, innovations, and discussions taking place across the field of genitourinary cancers, including prostate cancer, bladder cancer, kidney cancer, and testicular cancer. This podcast is led by Cancer.Net Associate Editor for Genitourinary Cancers, Dr. Petros Grivas. Dr. Grivas is the clinical director of the Genitourinary Cancers Program at University of Washington Medicine and a professor in the clinical research division at the Fred Hutchinson Cancer Research Center. He is joined by Dr. Neeraj Agarwal, Dr. Shilpa Gupta, Dr. Tian Zhang, and Dr. Timothy Gilligan. Dr. Agarwal is a Professor of Medicine, and a Presidential Endowed Chair of Cancer Research at the Huntsman Cancer Institute at the University of Utah. He directs the Genitourinary Oncology Program and Center of Investigational Therapeutics at the Huntsman Cancer Institute. He is also the Cancer.Net Specialty Editor for Prostate Cancer. Dr. Gupta is the Director of the Genitourinary Medical Oncology Program at Taussig Cancer Institute and Co-Leader of the Genitourinary Oncology Program at Cleveland Clinic. She is also the Cancer.Net Specialty Editor for Bladder Cancer. Dr. Zhang is an Associate Professor of Internal Medicine at UT Southwestern Medical Center and a medical oncologist at the Harold C. Simmons Comprehensive Cancer Center. She is also the Cancer.Net Specialty Editor for Kidney Cancer. Dr. Gilligan is a Medical Oncologist, Associate Professor of Medicine, and Vice-Chair for Education at the Cleveland Clinic Taussig Cancer Institute. He is also the Cancer.Net Specialty Editor for Testicular Cancer.  View full disclosures for Dr. Grivas, Dr. Agarwal, Dr. Gupta, Dr. Zhang, and Dr. Gilligan at Cancer.Net. Dr. Grivas: Hello. I'm Dr. Petros Grivas. I'm a medical oncologist in Seattle, a professor at the University of Washington and Fred Hutchinson Cancer Center. I'm really excited and thrilled today to host wonderful superstars in the field of GU Medical Oncology who will share insights about the highlights of kidney cancer, prostate cancer, and bladder, urothelial, urinary tract cancers that happened in 2023. And this highlight aims to inform our great audience about what are the clinically relevant insights, what patients should be aware, what patients should ask for when they go to the clinic, or overall, how they can be most well-informed and have the necessary tools to improve their care and feel well-supported in regards to education. So without further ado, we're going to cover in first prostate cancer, a very important update in this year. So all the people out there that are interested in hearing about prostate cancer will find this very, very useful and insightful. I'm very excited to host Professor, Dr. Neeraj Agarwal from University of Utah. Neeraj, do you want to introduce yourself? Dr. Agarwal: Of course. It's such an honor to be here. My name is Dr. Neeraj Agarwal. I'm a professor of medicine and director of genitourinary oncology program at the University of Utah Huntsman Cancer Institute. Dr. Grivas: Neeraj, thank you so much for accepting the invitation and being with us. I would like to ask you, what's your take on the current state of genetic testing in patients with prostate cancer? And when we say genetic testing, maybe you can clarify the distinction between germline and somatic and comment on both if you could. Thank you. Dr. Agarwal: Of course, a very important topic. I must tell you that it is very clear from all the guidelines that in patients with advanced prostate cancer or metastatic prostate cancer, meaning when prostate cancer has spread to different parts of the body, both germline testing to look for hereditary mutations in the DNA repair genes and testing for the same genes inside the tumor tissue are considered standard of care. So, a patient with advanced prostate cancer should have germline testing and somatic tumor tissue testing to look for mutations that can predispose them to have prostate cancer, and if they have genes in the tumor which can be targeted by the current approved drugs, like drugs which are already approved right now or which are in clinical trials. Unfortunately, less than 50% of patients in many areas of the country and in the world, less than 20% of patients are being tested. And even more, unfortunately, patients are less likely to be tested are those who are not well-resourced, who are not living in rich countries, if you will. They are poor- or low-resourced countries. Even with high-income countries, within those countries, patients who are living in relatively not-so-affluent neighborhoods, they are less likely to be tested. From racial perspective, patients who are Black or who are Hispanics are less likely to be tested. Based on how many drugs are out there in the clinic and emerging through clinical trials. And the fact that we can use many of these mutations for prognostication, to inform survival, to inform aggressiveness of the disease. It is not only to treat those patients, but also how to monitor the disease. The genetic testing is very important. Dr. Grivas: Thank you so much, Neeraj. It's very insightful. And I think you did a great job outlining the clinical relevance for both the patient in terms of treatment decision-making and therapy options, especially for advanced prostate cancer, as well as the broader family and implications for cancer prevention and cancer screening for the broader family members. So definitely a very important topic. Neeraj, the other question I have, if you could tell us more about this class of medications called PARP inhibitors. If you can comment on the currently approved PARP inhibitors, either as a single agent, what we call monotherapy or combination therapies for patients with prostate cancer in the United States, and who is eligible to receive those therapies? Dr. Agarwal: And this is such a nice segue to talk about PARP inhibitors as we were just talking about genetic testing of prostate cancer. So, PARP inhibitors are a class of drug which are instrumental, critical in treatment of patients who harbor mutations in those DNA repair genes. And two monotherapies, meaning using these PARP inhibitors as single agents have been already approved in the United States and several other countries. These are olaparib or rucaparib. Olaparib is approved after patients have had disease progression on novel androgen-blocking therapies or androgen blockers such as enzalutamide or abiraterone or apalutamide. And these PARP inhibitors such as olaparib or rucaparib can be used for those patients as single agent if they have these DNA repair mutations. Now, last year, we saw several combinations of PARP inhibitors with these androgen or novel hormonal therapy, as we call them. And these include abiraterone plus olaparib, abiraterone plus niraparib, and talazoparib plus enzalutamide from various phase 3 trials. Now, I'd like to bring to your attention that these PARP inhibitor combinations are approved with different indications in the United States and in the European Union. And they continue to get approved in various other countries. So the combination of abiraterone and a PARP inhibitor, whether it is olaparib or niraparib, they are approved for patients who have new metastatic castrate-resistant prostate cancer, and they have BRCA1 or BRCA2 mutations in the cancer cells or they have germline BRCA1 and BRCA2 mutations. Enzalutamide and talazoparib combination is approved in the United States for patients with metastatic castration-resistant prostate cancer with BRCA1 and BRCA2 mutations, but also several other DNA repair gene mutations. And that's a big difference as far as approval is concerned in the U.S. In the European Union, for our patients who are listening from European Union, the combination of abiraterone and olaparib and enzalutamide and talazoparib are approved for patients with metastatic castrate-resistant prostate cancer where chemotherapy is not clinically indicated, regardless of whether they have mutations in the DNA repair genes or not. And the combination of abiraterone and niraparib is only approved for patients with metastatic castrate-resistant prostate cancer with BRCA1 and BRCA2 mutation. So I just wanted to outline the different indications in the United States and in the Europe. Dr. Grivas: Thank you so much, Neeraj. So eloquent and very relevant to multiple patients globally, as you pointed out, with some differences in terms of the regulatory approval and availability of those agents in different countries. So great insights. Maybe we'll ask you 1 more question again since we are doing the highlights of the year. Another very important area of therapeutic development has to do with these novel agents that target the prostate cancer cells, and we call them theragnostics as a broader term. And I will let you explain what that means maybe in lay terms for our audience. And specifically, if you can comment on the recently presented PSMAforetrial at the ESMO meeting in Madrid with lutetium-177 PSMA. What are the implications of these results for our patients, and what is the role of lutetium therapy in this particular therapy setting? Dr. Agarwal: Of course, very important and pertinent topic indeed. As our patients may know that lutetium-177 therapy, or simply speaking, lutetium therapy, has already been approved for patients with metastatic castrate-resistant prostate cancer who have had disease progression on this novel hormonal therapy and a chemotherapy with docetaxel or cabazitaxel. And this indication is already there in the U.S. and in various other countries. And patients are eligible to receive lutetium therapy as long as their disease has progressed on docetaxel or one of the taxane chemotherapy and a novel hormonal therapy. Now, in the European Society of Medical Oncology meeting, Dr. Oliver Sartor presented the data on PSMAfore trial where lutetium therapy was used before chemotherapy. In this trial lutetium therapy was compared with another novel hormonal therapy after disease progression on 1 novel hormonal therapy. And there was approximately 6-month improvement in progression-free survival, meaning there was a delay in disease progression by 5 to 6 months in patients who were receiving lutetium therapy. And at the time of the report, there was no improvement in overall survival, with the caveat that 84% patients who were receiving novel hormonal therapy, actually, they switched over to lutetium therapy after disease progression. So, overall, survival data may not be met. Having said that, we already know that lutetium therapy is an effective therapy, and it has a definitive role in treatment of our patients with metastatic castrate-resistant prostate cancer. Dr. Grivas: Thank you, Neeraj. That's very, very important data. And I'm so glad we have many more therapy options for our patients with prostate cancer. So involvement and accrual in clinical trials, I'm sure you will agree, is a very important and high priority. And I always encourage people with prostate cancer to ask about clinical trials that are relevant to their situation. Dr. Agarwal: Yeah. I'd just like to add a point regarding lutetium therapy that there was a phase 2 trial in from Australia which compared lutetium therapy with cabazitaxel therapy after disease progression and docetaxel chemotherapy. And efficacy of both agents were not very different. So just wanted to make that point. Dr. Grivas: Thank you, Neeraj. It's a very important point. And obviously, always want to think about pace and preference, convenience, distance from the cancer centers, all the relevant points, how we can individualize suggestions or recommendations for our patients. Thank you so much, Neeraj, for your wonderful input, insights, and all the work you do in the field. Dr. Agarwal: Thank you very much for having me. Dr. Grivas: Of course, of course. And now we're going to transition to a different cancer type. We're going to talk about bladder cancer and urothelial cancer in general, urinary tract cancer. And we're delighted and excited to have Dr. Shilpa Gupta from Cleveland Clinic, who's a professor there of oncology. Shilpa, I want to introduce yourself? Dr. Gupta: I'm Shilpa Gupta. I'm a genitourinary medical oncologist and the director of the GU Program at Cleveland Clinic. I'm really excited to be doing this podcast with you all. Dr. Grivas: Thank you, Shilpa. You have done amazing work in the field, pushing the field forward. You are part of those transformative studies. I will ask you in the beginning where I'm going to focus my first question for people who have advanced or metastatic bladder cancer or urinary tract cancer or upper or lower tract. And we saw really exciting, impressive data at the recent ESMO Congress in Madrid a couple of months ago. And I know you were there and were enjoying to see the improvement in patient outcomes that comes with better quality of life for patients in the last several years. And the question I have for you, if you want to summarize the key data in the first-line treatment, patients who have no prior treatment for metastatic urothelial cancer, what are the key data we showed at the ESMO meeting? Dr. Gupta: Thank you, Petros. As you said, this is a really exciting time for both patients as well as the physicians treating bladder cancer because of all the new developments which we've seen after decades. So at ESMO 2023, we saw the key data from the EV-302 trial, which was a phase 3 trial, which randomized patients to the standard of care, platinum-based chemotherapy, gemcitabine-cisplatin or gemcitabine-carboplatin, versus a novel drug, which is an antibody-drug conjugate called enfortumab vedotin and the immunotherapy pembrolizumab. And the primary endpoint was to see if patients lived longer and this delayed progression. And we saw that in this the progression-free survival, we saw that it was 12.5 months with enfortumab vedotin and pembrolizumab compared to 6.3 months, which means that the risk of progression or death was decreased by 55% with this new combination. And the benefit was seen across all the various factors, especially patients with liver metastases, visceral metastases, whether or not they had contraindications to receiving cisplatin or not or PD-L1 expression. So this is the first time we saw such a remarkable benefit with any treatment that beat platinums. And the overall survival was also doubled: 16 months in chemotherapy versus 31.5 months with this combination. So the risk of death was reduced by 53%. And we also saw that the overall response rates were 68% with this compared to 44% with chemo. And 29% of patients had complete responses. And this was really remarkable because we have not seen such data before. And in the same session, we also saw another phase 3 trial that was presented, which was the Checkmate 901 trial, in which the investigators tested whether the addition of immunotherapy called nivolumab to the standard of care, gemcitabine and cisplatin was better than gemcitabine and cisplatin alone. So this was a study only looking for patients who can receive cisplatin. So patients were randomized to 6 cycles of gemcitabine cisplatin versus nivolumab, gemcitabine cisplatin for up to 6 cycles. And after that, they continued nivolumab maintenance every month for up to 2 years. And in this, the primary endpoint of overall survival was also met, although the difference was not as huge as the other study. It was 18.9 months with chemotherapy versus 21.7 months with the combination. And progression-free survival was also improved by just 0.3 months with the combination. And the objective response rates were higher with the combination, 57% versus 43%, and there were 21% complete responses. So the bottom line is that both these trials showed us that the frontline treatment is not going to be just platinums anymore moving forward. We will have the option of the enfortumab vedotin and pembrolizumab for all comers, patients who can get platinums, and nivolumab and gemcitabine cisplatin for patients who are cisplatin eligible. Dr. Grivas: Thank you, Shilpa. Wonderful summary. Really, really exciting time to see the field moving forward and translate those results to longer life for our patients. In that context, I will also ask you—I asked Neeraj before about genetic testing in prostate cancer. I will ask you a similar question about genetic testing in bladder cancer. Again, reminding the audience about the distinction between germline testing, which is the DNA we are born with, and somatic testing, which is the cancer-specific genomic changes. Could you comment on the importance of genetic testing in bladder cancer? Dr. Gupta: Yes. Absolutely, Petros. Genetic testing in urothelial cancer is very important because for the first time a few years ago, we saw a drug targeting the fibroblastic growth factor receptor or FGFR alterations. This drug is called erdafitinib. It is the first targeted therapy to be approved in urothelial cancer. It is only seen in up to 20% of patients who harbor these alterations for whom this option may be viable. And we saw initially that erdafitinib was approved in patients who harbor these alterations in the phase 2 BLC2001 trial where it showed response rates of 40% and encouraging progression-free survival, and overall survival. And then we also saw in a phase 3 trial called the THOR trial where patients who harbored these alterations by genetic testing, erdafitinib was much better than chemotherapy, prolonged survival by almost 4.2 months compared to chemotherapy. So unless we are testing, we won't find this. So it is really important to test all our advanced disease patients so we are not depriving them of this additional targeted therapy. Dr. Grivas: Thank you, Shilpa. Very important message for our patients to definitely discuss the value of genetic testing. And if we think about therapy implications, specifically genomic changes, DNA changes in these FGFR-2 and FGFR-3 genes are very relevant and important for potential therapy with this agent called erdafitinib. Shilpa, a quick comment. We saw data from THOR cohort 2 comparing erdafitinib with this inhibitor of this FGFR that we just talked about compared to pembrolizumab, which is an immunotherapy drug inhibiting a checkpoint of the immune system. Could you quickly comment on that? And I think both options are available for our patients and sometimes just comes down to the sequence based on a particular patient case. Dr. Gupta: So Petros, as we had thought that patients who harbor these alterations in their tumors, they may benefit from using targeted therapy before immunotherapy. That was the premise of the cohort 2 of the THOR trial, that patients will do better if they received erdafitinib first after progressing on 1 prior line of therapy, which is not an immunotherapy. So patients were randomized to erdafitinib versus pembrolizumab. Of course, all of them had to have the FGFR alterations. The primary endpoint was overall survival. Initially, like I said, the study assumed that there'll be 46% improvement in overall survival with erdafitinib over pembrolizumab. However, the study was a negative study. There was no difference in the overall survival. And what that means for our patients is that erdafitinib right now is positioned for patients who've had prior platinums and immunotherapies. So erdafitinib should not be used before immunotherapy. So I think this is the first study that really settles the question of sequencing for our patients. And I think the message is that in a patient's journey, they should be getting all these therapies. We just now know that it's better to use pembrolizumab before erdafitinib and not vice versa. Dr. Grivas: Thanks, Shilpa. And then really, really interesting to see these trials being reported. And as you said, individual discussion with the patients and the response rate may be another factor to consider. If someone wants to have a more rapid control of the cancer of the disease, we may potentially think about an agent with high response rate and vice versa. So I think to your point, individual decisions. And I think patients asking those questions is very important in the clinic to help select the right patient for the right treatment for the right patient. Dr. Gupta: Yeah. Absolutely, Petros. They did see that the response rates were 40% with the erdafitinib versus 21% with the immunotherapy. So using that information can sometimes guide us if a patient has high disease burden. Dr. Grivas: Thank you, Shilpa. That was very insightful. And thank you for all you are doing for the patients and the field in general. You really, really have helped the field move forward. So congratulations and thank you. And we're going to transition to another superstar in the field of GU cancers. Very excited to host Dr. Tian Zhang. Dr. Zhang is in UT Southwestern in Dallas. Tian, you want to introduce yourself? Dr. Zhang: Hi, Petros. Thank you so much. Tian Zhang, I'm a GU medical oncologist and associate professor at UT Southwestern Medical Center in Dallas. Dr. Grivas: Wonderful. Thanks, Tian. Again, the same comments. All the work you're doing in the field is tremendous. Thanks for joining us today. Tian, we saw some very interesting data at the ESMO meeting. And since we're doing the highlights of the year, I think the predominance of the data we saw at the ESMO meeting was about this drug called belzutifan, where I will ask you to enlighten us what exactly this is. And particularly, we saw 3 different trials. I would probably ask you to focus more on the LITESPARK-005. What was the trial design and what was the primary goal of the study? When patients go on this drug, what they should be aware in terms of side effects? And what was all this discussion that the take-home message at the end of ESMO regarding belzutifan? Thank you. Dr. Zhang: Sure. We'll parse that one at a time. Belzutifan, I hope many of our audience knows is a small molecule inhibitor of the HIF complex, a hypoxia-inducible factor complex, which is implicated in the development of kidney cancers. And this biology actually contributed to the Nobel Prize in 2019. Understanding the structure of the HIF complex and how to target it. For a long time, HIF was thought to be un-targetable. And so the fact that there were small molecules identified actually here in Dallas at UT Southwestern that inhibits the dimerization of the HIF complex is really novel and shows us the bench-to-bedside translatability of these preclinical discoveries. And so there were a couple of molecules that were discovered here on campus and they paved the way for what became molecules that have now made it to clinic, in particular belzutifan. And so we've had belzutifan now approved for Von Hippel-Lindau Syndrome over the last 2 years or so. So many of us are familiar with using this drug in the clinic. It's an oral agent that's able to target the HIF complex and block it and really control the spread of clear cell kidney cancers, in particular in Von Hippel-Lindau disease.  LITESPARK-005, the trial that you're alluding to, there was a registrational trial for belzutifan across other kidney cancer populations. And this trial was the 1 that made, I think, the biggest impact of the 3 trials that were presented at ESMO this year.  LITESPARK-005 was a phase 3 trial of patients who had metastatic or locally advanced clear cell kidney cancer who had progressed after prior systemic therapies, not more than 3 prior lines. And they were randomized to either belzutifan at the 120 milligrams daily dose or everolimus at the 10 milligrams daily dose. And the primary endpoint was delay of progression. So progression-free survival as well as overall survival. So we saw the primary endpoint of these was met for progression-free survival. There was about a 26% risk reduction for progression for patients treated with belzutifan versus those that were treated with everolimus. The objective response rate I would highlight is also significant for the patients treated with belzutifan. There was actually a 3.5% complete response rate and objective responses. So including partial responders was about 23%. I would say that patients who are treated with belzutifan need to be aware of the side effects of anemia and also hypoxia [low levels of oxygen in the body]. And in fact, higher grades of anemia can occur in up to a third of patients and higher rates of hypoxia. So low oxygen saturations can occur in up to 10% or so of patients. And so that's really important when we're thinking about those toxicities and how we might hold or support the side effects with growth factors, for example, for the anemia. Otherwise, it's quite well tolerated as a single agent. As you alluded to, there was 1 controversial aspect of this particular trial because the control cohort was treated with everolimus. And everolimus as a single agent may not be what people use at this point in the refractory setting. But it is an acceptable approved treatment option for patients in the refractory kidney cancer setting, and therefore, it was chosen as the control cohort. And belzutifan did improve compared to a known standard of treatment. So I think that's really important to add to our armamentarium in refractory disease. Dr. Grivas: Wonderful, Tian. Thank you so much for a really, really comprehensive and detailed review. We'll have to see whether it will be available for patients with advanced clear-cell kidney cancer. To your point, it's already available for patients with this condition that you mentioned, the Von Hippel-Lindau genetic condition. So it's great to see more options available for our patients. Maybe I'll ask you another quick trial to comment on Tian, and I'll ask you individual questions to make it easier, to your point, for the audience to follow. And I'm referring to the RENOTORCH trial. This was conducted in China, and I think it was practice-changing there. Could you tell us the study design? Dr. Zhang: RENOTORCH was another phase 3 randomized trial. It was conducted all in China of patients with unresectable metastatic clear cell kidney cancer, no systemic prior therapy, and also intermediate- and poor-risk disease by IMDC criteria. So these were all first-line metastatic disease, and patients were randomized to either toripalimab, which is their PD-1 inhibitor, plus axitinib versus sunitinib. So this is a trial design that mirrors many of our prior trials in the first-line metastatic setting that have led to approvals of VEGF IO [immunotherapy] combinations. But this is the first one that was carried out purely in the Chinese population and important for the Chinese population to gain access to these types of combinations. Dr. Grivas: Thank you, Tian. Very important to see this global approach, as you mentioned, oncology and see trials from different countries. What were the main findings of this trial? Dr. Zhang: Sure. The primary endpoint was progression-free survival of the 2 cohorts. And they randomized about 420 patients. About 80% per cohort had intermediate-risk disease. And the combination of axitinib with toripalimab did improve progression-free survival. So it had a 35% risk reduction for progression over time. So it did meet its primary endpoint. Dr. Grivas: Thank you, Tian. It's great to see progress in the field. As I mentioned, new agents, positive trials. Could you comment a little bit on the side effect profile and the significance of this trial for our patients worldwide? Dr. Zhang: Sure. When we're talking about VEGF IO combinations very similarly as to the prior trials that we've seen in the toxicity profiles, we're thinking a lot about the immunotherapy toxicities of rashes and colitis [inflammation of the colon], endocrinopathies [hormone problems], as well as the rare inflammatory reactions of the liver, lungs, or kidney, but also added in the small molecule effects of hypertension, hand-foot syndrome, and mucositis [mouth sores] and taste changes. So very important to think through those side effect profiles as our patients are being treated with these combinations. Dr. Grivas: Thank you so much, Tian. Great to see, again, this progress made worldwide. And I think it speaks to the idea of how we can have equitable healthcare delivery across the globe, right, and have agents accessible in different parts of the world. Dr. Zhang: Absolutely. In fact, I would just add that the Chinese population haven't actually had access to drugs like cabozantinib. And this is their first phase 3 grade 1 evidence for a combination of VEGF with IO combination. So it's really important that these trials are carried out in the populations where we try to find the effect and see that the consistent benefit is there so that those patients have access to all of these treatment options. Dr. Grivas: Thank you, Tian. I appreciate your wonderful insights and all your amazing contributions in the field and your research. It's really, really inspiring to see. And I'm going to transition now. Last but not least, we're having the honor of hosting professor, Dr. Tim Gilligan, who is in Cleveland Clinic, and Tim is a world-known expert in urinary cancers, including testicular cancer. Tim, would you like to introduce yourself? Dr. Gilligan: Yes. Hi. So I think you just did. Tim Gilligan, an oncologist at Cleveland Clinic. I chaired the NCCN panel on testis cancer and edit the UpToDate sections on testis cancer with their help. Dr. Grivas: Fantastic. Thanks, Tim, for being with us today. And all the work you have done for our patients with GU cancers, testicular cancer, and a lot of work is being done with the NCCN and other guidelines. And you are co-chairing the NCCN guidelines, to your point. Tim, a lot of discussion is happening nowadays across cancer types regarding the role of what we call biomarkers, which are potential features that can help us select patients for the right treatment or help us estimate the prognosis, how long people live. Could you comment a little bit on this biomarker called microRNA in patients with testis cancer? How do you envision this being developed in the future? Is it ready for prime time or not yet? Dr. Gilligan: And that's an important question. It's not ready for prime time yet, but we are making progress. There are a couple of areas where it could be very useful. So for example, in stage I testicular cancer, we tell patients to go on surveillance because they're usually cured with orchiectomy [surgical removal of the tumor and testicle], but there is a risk of relapse, and that risk of relapse is highly variable. And our current risk stratification systems for predicting who's going to relapse, who has stage 1 disease, are helpful, but they're far from perfect. And so there was data presented this year that mRNA may be more accurate at predicting for men with stage I non-seminomas who's destined to relapse. And so the implication of that would be if you are positive for mRNA, this particular mRNA for non-seminoma and you have stage I disease, normal scans, normal markers, you could identify a high-risk group of patients who maybe should get a cycle of BEP chemotherapy rather than waiting. If you know they're going to relapse, you're going to have to get them 3 cycles of BEP, why not just treat them right away? Or maybe RPLND [retroperitoneal lymph node dissection] could be helpful in that setting. We don't know. But we would need to do studies validating that approach. There is data showing that it does predict relapse, but it's not at the point of saying, "Are the patients really going to do better with immediate treatment and which treatment is going to be best for them?" But I thought that was an important finding and really an example of how we think we're going to use it, which is to find relapse a lot earlier and so that we can give a less toxic treatment. And the benefit of that is that we know more and more that chemotherapy is toxic and resulted in second cancers. For men who get multiple cycles of cisplatin-based chemotherapy, or if they get radiation therapy, they're at higher risk of dying of other cancers than the general population. So if this could help us find early relapses, treat it more gently, less aggressively, have late, less toxicity, and the same cure rate. That would be great. So we're not there yet, but I think we're going to get there. Dr. Grivas: Thanks, Tim. Very, very helpful to know. So this microRNA 371 that we talk about is not ready for prime time, but you definitely see promise for the future, and more trials, more studies are being done. Again, illustrating the importance of clinical trials that can help us evaluate the added value of a particular biomarker, including this particular microRNA that we talked about. Dr. Gilligan: Before you change the subject on getting to crude biomarkers, there was also an interesting abstract showing that for stage I seminoma. If we actually use our current markers, we may be able to predict much more accurately. And it'll be interesting to see if that changes. They looked at the variables of lymphovascular invasion, invasion of the hilum of the testis, whether or not preoperative markers were elevated, LDH, and beta HCG. What was interesting to me about that paper was that this is about 900 patients. It was pretty large. That if you had all 4 risk factors, the relapse rate was about 64%. Whereas your average relapse risk for stage I seminoma is about 15%. We put everyone on surveillance. If we started if that model is persuasive to the community and starts getting used, then maybe patients with those 4 risk markers who most of whom are going to relapse, according to this data, maybe you want to treat those people and not put them on surveillance. So that'll be interesting to follow up on too. Dr. Grivas: Thanks, Tim. And you are referring to currently available blood tests, right, that can be used, and we use them in clinical practice. So we just put them together, try to get a sense of the chance of cancer coming back, what we call recurrence, and how long people may live. That can help us make a therapy decision. Thank you, Tim. This is very, very interesting. And I'm glad to see the progress in the field. I think you alluded to that before, but there is a trend discussing when we have a removal of the testicle for a patient with testis cancer, what to do next, depending on the stage, those markers that the blood tests you told us about. What about the role of surgery for removal of lymph nodes, for example? And do you see a trend going forward that in many selective cases, certain scenarios, we may potentially select surgery as opposed to chemotherapy or radiation to avoid these potential complications down the road? And if so, which are those patients who may benefit from surgery? Dr. Gilligan: Yeah, an important question. I think surgery, there's been a growing interest in using surgery rather than chemotherapy in order to avoid late effects. So retroperitoneal lymph node dissection (RPLND) is the most obvious example of that. There is data now showing that most patients with stage II seminoma can be cured with retroperitoneal lymph node dissection. We used to treat those patients with chemotherapy or radiation, but as I've noted, both of those are associated with an increased risk of second cancers down the line. So there are papers on both sides of the Atlantic showing that you can cure most people. However, it is important to note that the relapse rate after surgery is significantly higher than the relapse rate after chemotherapy or radiation. If you take a stage II patient and treat them with chemotherapy or radiation, you're going to cure well over 90% of them. Whereas the relapse risk with surgery, depending on what you find at surgery, is going to be higher. So on average, it's going to be in the realm of 20%, maybe as high as 30%, depending on which paper you look at. And if you take patients who have PN2 disease, so a lymph node is 2 centimeters or bigger, 25% or more of those patients are relapsing after surgery. So it's important for patients to understand that this treatment has the benefit of avoiding chemotherapy for most patients, but it also has a higher risk of relapse than the old treatments. We still think it's attractive because if you can avoid chemotherapy in 3 out of 4 patients or 4 out of 5 patients, that's a benefit to those patients. And also, if you go in and find a significant amount of cancer at surgery, you can give 2 cycles of chemotherapy right away and almost eliminate the risk of relapse, which is less chemo than they would be getting upfront, which would be 3 or 4 cycles. So one of the emphasis now is really trying to avoid late toxicities if we can. You sometimes see that even in the metastatic setting in terms of resecting residual masses and situations where we maybe in the past would have thought about second-line chemotherapy. I think people are more thinking about opportunities to use surgery instead to try to limit the quantity of chemo that we're giving. Those are much trickier decisions than the stage II decisions, but definitely a growing interest in surgery rather than chemo. Dr. Grivas: Thank you so much. It's really, really exciting to see that testis cancer was really transformed in the past with developments of therapies like chemotherapy, radiation therapy, and surgery. And it's great to see this evolving down the road. And I think all of the above that you mentioned evolves through the conduction of clinical trials. And as I mentioned before, I think it's so important to give the opportunity for patients and families to review clinical trial options. I think it's critical to try to help them, but also help other patients, the community, the society in general. So I always try to underline the importance of clinical trials across the board. And on that note, I think we had such a successful year, 2023 across GU cancers. It's so great to see the progress being made. All of us are looking forward for more exciting research being done in 2024 and beyond. And on that note, I want to thank so much Dr. Agarwal, Dr. Gupta, Dr. Zhang, and Dr. Gilligan for wonderful insights and all the great work they're doing in the field of GU cancers. As the editor for the GU Cancers for the wonderful Cancer.Net, I'm so proud of this team and really, really looking forward to further podcasts like this and how we can better serve the educational mission for ASCO, working with the wonderful staff at Cancer.Net. Thank you so much, all of you, for your time today and all you are doing. Dr. Gupta: Thank you, Petros. Dr. Zhang: Thank you, Petros. ASCO: Thank you, Dr. Grivas, Dr. Agarwal, Dr. Gupta, Dr. Zhang, and Dr. Gilligan. You can learn more about new research in genitourinary cancers at www.cancer.net. Cancer.Net Podcasts feature trusted, timely, and compassionate information for people with cancer, survivors, and their families and loved ones. Subscribe wherever you listen to podcasts for expert information and tips on coping with cancer, recaps of the latest research advances, and thoughtful discussions on cancer care. And check out other ASCO Podcasts to hear the latest interviews and insights from thought leaders, innovators, experts, and pioneers in oncology. Cancer.Net is supported by Conquer Cancer, the ASCO Foundation, which funds lifesaving research for every type of cancer, helping people with cancer everywhere. To help fund Cancer.Net and programs like it, donate at CONQUER.ORG/Donate.

Drs. Eric Small, Anthony Zietman, and Eric Klein share their reflections as founders of the ASCO Genitourinary Cancers Symposium and discuss key moments in the Meeting's development, its role in advancing GU cancer research, and major challenges ahead for the field as the Symposium celebrates its 20-year anniversary. TRANSCRIPT Dr. Eric Small: Hello, and welcome to the ASCO Daily News Podcast. I'm Dr. Eric Small, your guest host of this ASCO Daily News Podcast today. I'm the co-leader of the UCSF Prostate Cancer Program and deputy director and chief scientific officer at the UCSF Helen Diller Family Comprehensive Cancer Center. This year, quite amazingly, we're celebrating the 20th anniversary of the ASCO Genitourinary Cancers Symposium, which is hosted annually in San Francisco. The Symposium has heralded some of the biggest strides in GU oncology and has the largest multidisciplinary, global audience for GU cancer research. I was honored to have a role in the development of ASCO GU two decades ago, along with my friends and colleagues, Dr. Eric Klein, emeritus professor and chair of the Glickman Urological and Kidney Institute at the Cleveland Clinic. And Dr. Anthony Zietman, a professor of radiation oncology at Harvard Medical School and the Massachusetts General Hospital. On today's episode, we'll be reflecting on key moments in the meeting's development, its role in advancing GU cancers and GU cancer research, and major challenges that lay ahead for the field. You'll find our full disclosures in the transcript of this episode, and disclosures of all guests on the podcast are available at asco.org/DNpod. Eric and Anthony, I'm delighted to have this opportunity to catch up with you both to discuss ASCO GU, thank you for coming on the podcast today. Dr. Eric Klein: Thanks for having us. Dr. Anthony Zietman: Thanks for the invitation. Dr. Eric Small: Well, it's really exciting and it's wonderful to see the two of you. So, the ASCO GU Symposium has been a key annual event for all of us in the GU field. But to give our listeners some background, when the Symposium was first created, when we first met in San Francisco, starting on Thursday, February 17, 2005, it brought together 1,035 individuals interested in the prevention and treatment at that point of prostate cancer alone. At that time, the meeting was co-sponsored by ASCO, the American Society for Therapeutic Radiology and Oncology or ASTRO, the Society of Urologic Oncology (SUO), and the Prostate Cancer Foundation. It was actually the culmination of several years of planning. Clearly, it represented the first truly multidisciplinary scientific and educational meeting dedicated solely to prostate cancer, and we'll come back to talk about that. The meeting went back and forth between San Francisco and Florida for a few years before finally, settling permanently in San Francisco. In the last 20 years, ASCO and the Symposium's co-sponsors expanded the meeting to include all genitourinary specialties. This year, ASCO received more than 875 abstract submissions and anticipates that there will be even more attendees than last year. On a personal note, it's truly amazing to me that here we are, 20 years later, and the meeting is going stronger than we could ever have imagined. I must say that my motivation to help organize this meeting stem from two issues that were somewhat in tension with each other. First, the field of prostate cancer and prostate cancer research was just starting to take off at the time, and we really needed, as a community, a venue where across disciplines, we could talk and meet with each other. But that was in real tension, at least at ASCO, where we were relegated at the Annual Meeting to a tiny room at the far end of the convention center on the last day of ASCO, because really, that's all we could muster. And I do remember making a pitch, assuring folks that there was an unmet need, and that the field was going to take off, who knew? So, I'm wondering, and either of you can jump in (Dr. Klein, Dr. Zietman), tell us how you got involved in the first GU meeting, and what's the most salient feature of your involvement? Anthony, do you want to start? Dr. Anthony Zietman: I think it's really important to discuss the historical context at which this meeting was born. Back in the 1990s, we were incredibly polarized as specialties in GU oncology. PSA had been introduced in the late '80s, early '90s, screening was everywhere. There was a tidal wave of patients and an almost reckless race to treatment. All surgeons believed that all patients with localized early prostate cancer needed surgery and that they could do individually, a beautiful job. And all radiation oncologists believed that they could deliver morbidity-free treatment and could do it to everyone regardless of your age or stage. And there were a few, there were a few who thought maybe we didn't need to screen everyone, and maybe there was a little bit of overtreatment, maybe we've gone a little bit too far, but those voices were really suppressed in the '90s. Those voices didn't have a voice. Many of us also believed there was more morbidity to our treatment than we'd appreciated. And that was the media in which, us three, all young research physicians, probably all in our low forties were given the charge of this meeting. And the thing I most remember about it in the planning, is that we actually decided collectively to give voice to everyone, including maverick voices. It wasn't just about the party line, and it wasn't just about the North American line, there were Britts and there were Swedes, and there were Dutchmen who had very important things to say as well, and very, very different perspectives. And we also chose to give voice to young people as well as just our party elders, so to speak. I don't know which of us, if any of us, or maybe it was our society suggested but we do it all in a single room such that rad oncs and surgeons were all together, and it led to a kind of forced truthfulness, which started to break down this groupthink that we developed in our own silo. So, when I look back, I think that that context was very important and that what we sought as young program chairs was we sort of tapped in something that was latent in our field. Eric KIein, I don't know if you remember things as I did. Dr. Eric Klein: I do. And things were very siloed then. We had hired early in the mid-90s, I think, a young radiation oncologist named Pat Kupelian, who became a close collaborator and a good friend, and who really changed the narrative around treating prostate cancer at the Cleveland Clinic, which was all surgical prior to that time. And he did such high-quality work, it was hard not to pay attention. And he actually took it on himself in his early years when he wasn't very busy to sit down and go through all the patients that we had treated with prostate cancer at the Cleveland Clinic, radiation versus surgery, and had the temerity to write a manuscript that showed that there was no difference in survival, based on PSA biochemical recurrence and metastasis and that sort of thing. And that was sort of game changing. And it really clued me into the fact that for patient's sake, we needed to be talking to our colleagues. The second perspective was from the perspective of having attended a couple of Prostate Cancer Foundation meetings. And I think they really deserve credit for increasing the visibility of prostate cancer research, and funding it and recruiting really good scientists from other disciplines. When young scientists were told, and we heard this repeatedly, "Don't spend your career researching prostate cancer, it's a dead end." And PCF did a great job of having a multidisciplinary meeting, which was smaller and not so clinically focused, but also got me excited. Dr. Eric Small: I think you're right, Eric. And I think that the transdisciplinary nature, as Anthony pointed out was new, it was innovative. No one had really, really thought about it. It was at the margins in different meetings. Your comments about PCF, Prostate Cancer Foundation, resonate because we did take a page from their book in many ways although that meeting, as you point out, is much more basic research-focused. I don't know if you guys recall that first year, in fact, PCF was a co-sponsor. We actually had asked Mike Milken to give a talk and he did. And obviously, once we expanded to the broader GU cancers, it was less pertinent for PCF to be involved. But absolutely, I agree with you, Eric, they deserve credit. PCF, and the PCF involvement, was one of the things that changed. There's many things that are constant that haven't changed, even though the science clearly has evolved dramatically. And I'm wondering if you guys can comment on things that are the same. One thing that stands out for me: I had the opportunity to look through the agenda for the 2005 meeting. And right there, very prominently, was a special lunch session that we had designed for mentorship and career development for trainees and early career investigators, and that's still ongoing and others have modeled it. And I think that was one amazing feature of this. One of you, I think Anthony mentioned that we invited a lot of young people to speak and to be the path blazers, but we also did this career development piece, and it was a wonderful event. I wonder if either of you or both of you could comment on other things that you think are constants and you anticipate will always be there. Dr. Anthony Zietman: I think to me that constant is that every time I go, I hear speakers I've not heard before. Often very senior speakers, I've never heard them before. But it is the practice of GU ASCO to invite people that are outside your sphere of experience, which is very challenging. Dr. Eric Klein: Two things strike me. I think one is the international nature of the faculty. We tried very hard (and subsequent program directors have) to be very inclusive and to bring the work that was the most cutting-edge to the stage. There are lots of things that are done in Europe that started there sooner. PSMA treatment, for example, and many other ProtecT trial and many other things. And the debates on stage and how that gave the opportunity for every subspecialty to have the opportunity to share its perspective on particular case management issues and case management conferences, I think have been around forever. And maybe, the most valuable part of it all is to hear people's perspective on how to manage a particular patient. Dr. Eric Small: I think the other comment you made Anthony that resonated and still goes on, was it was a conscious decision to have a single session in one room where everyone attended. And not to do the usual small breakouts and concurrent sessions, but sort of the philosophy being, is we all need to hear the same thing, we all need to be in the same room at the same time. And it really fostered this transdisciplinary approach; it was truly educational for us. Now, it's sort of part of what we do, and part of what our patients expect of us. I think that bringing us all together into one room was really great. Dr. Anthony Zietman: But it's now so part of what we do, but it's difficult certainly for younger faculty and for residents to believe we ever did it any other way. But we did, and I don't know whether ASCO GU led that or reflected that, but that was the zeitgeist among young individuals like us. And it's really become the culture of contemporary practice. Dr. Eric Small: So, given that that's the culture now, which it is, and I think sure, we should take credit for it, at least in GU: why then is it important for people to continue to attend GU ASCO today if it's now our culture to do that? Dr. Anthony Zietman: For me, it's because we share information as equal partners in a multidisciplinary team. And our practice is so multidisciplinary and multi-modality these days that we can't exist alone, we no longer try to. Dr. Eric Klein: Nor can we. The amount of knowledge that's being generated in each subspecialty and it's spinoffs is so great. It's impossible for a busy surgeon to stay on top of that. And this is sort of one-stop shopping for everything that's really current and appropriate to know about. And again, I always look at these things from the patient perspective, and my ability to counsel patients about what their best treatment options might be, I thought more and more dependent, and I think today more and more depends on being knowledgeable about everything that's going on, and not just one narrow field that you happen to be an expert in. And that's why I think it's so important for youngsters to attend and even oldsters like us to attend to stay current. Dr. Anthony Zietman: Yeah, and also, multidisciplinary means so much more these days. It does mean oncologists and radiologists, information technologists. I mean, who knows what it'll mean in the future, but it's always expanding. Dr. Eric Small: And I think it's interesting, back when we did this, when we started it, we were worried about being able to fill one meeting with prostate cancer information - we did easily. It was not immediately clear that there was a role or room for additional GU cancers. And then there was an explosion both in kidney cancer work at first, and then bladder cancer. And now it's unbelievable how much is there. And perhaps, this meeting needs to be twice as long. So, I agree with you guys. I think that it's the best way to stay current. The other thing that I really appreciate about this meeting and others have a hard time doing it, is that it provides, as Eric indicated, for the busy clinician. It integrates sort of the important information that's coming in terms of more basic science and makes it readily available and digestible, which isn't always the case at pure science meetings and may or may not be apparent in other meetings. I, again, was looking at the preliminary agenda in 2005, we had asked Bill Nelson to talk about molecular targets or prevention, how forward-thinking. And that's continued to be the case that this is a meeting where you get that integration from the laboratory. Dr. Anthony Zietman: Well, and I would add to that, not just the integration of it, it's where now you get to hear things first. I mean, it used to be that, you went the AUA or ASTRO or ASCO to hear things. Now, everyone one wants to present it first at GU ASCO. Dr. Eric Klein: Yes, that's correct. Dr. Anthony Zietman: And I think we actually made it permissible in the early days that you could present at GU ASCO and at your specialty meeting. Dr. Eric Small: What are the challenges in the field that are going to likely shape the content of future meetings? And we've all alluded to the fact that the meeting is evolving and has done a really good job of staying current with the clinical science. But beyond that, what do you two feel are important areas that this meeting is likely to continue to address? Dr. Eric Klein: So, biomarker development has always been an important part of this meeting, and I think we need to broaden our view of what biomarkers are now, and in the AI era, digital pathology and AI-based models that predict treatment response and outcome. My hope is that they will be studied in a rigorous fashion, and that they will end up outperforming the kind of single biomarker approach that we've used in the past. And we need to understand that; we need to understand the science behind AI to a certain level, and we need to understand what questions AI can address, and how that might be useful. But I'm particularly excited about digital pathology where sampling error becomes less of an issue and the number of potential inputs you're looking at that are related to the output should increase exponentially. Dr. Anthony Zietman: And I would add on the AI side of things, as a former journal editor, when AI papers came into the journal, we actually didn't have enough people who could review them, who had the understanding to review these papers and tell us, "Is this a good paper or a bad paper?" So, we're going to need to increase our understanding of AI, Eric, as you said. So, I think that will be a push in the years to come. Also, on a very practical level, it is such a popular meeting, keeping us all under one roof and in one room, will become just difficult. But it's part of the culture of the meeting, and I think it's what people want. Dr. Eric Small: It's a good challenge to have. Dr. Eric Klein: Feeding everybody too. I recall one constant has always been really good breakfasts and lunches. Dr. Eric Small: Right, that has been a standard of ours. One of the interesting things that I think has changed, we saw glimmers of it back in 2005, but it was early on and it was, I think very early on in sort of a good understanding of social determinants of health and equitable access to healthcare and the challenges posed by incredible technology development and making sure that that doesn't increase disparities. And I think that that focus has increasingly been present in meetings and is not going to be lost. And it also speaks, one of you spoke to our international audience, that increasingly, I think this meeting is going to address urologic oncology and how we address it not only in developed countries, but in lower- and middle-income countries. And I think that will be a focus as well. I'm excited with what the future holds for ASCO GU. It has been an incredible run. I'm hoping that we'll be able to perhaps catalog some of the salient presentations that have been done at this meeting over the years, but there's no question as both of you have pointed out, this has become the venue. Well, thank you both for sharing your insights with us today on the ASCO Daily News Podcast. Really wonderful to see you both and talk with you. Dr. Eric Klein: Great to be here. Thanks. Dr. Anthony Zietman: Great to be here. Looking forward to the next 20 years. Dr. Eric Small: That's right. Dr. Anthony Zietman: If I'm still around. Dr. Eric Klein: Yeah, let's do this again in 20 years. That'd be great. Dr. Eric Small: We will. And thank you to our listeners for your time today. 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. Thank you. 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 and 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. Follow today's speakers:   Dr. Eric Small Dr. Eric Klein @EricKleinMD Dr. Anthony Zietman   Follow ASCO on social media:    @ASCO on Twitter    ASCO on Facebook    ASCO on LinkedIn      Disclosures:     Dr. Eric Small: Stock and Other Ownership Interests: Fortis, Harpoon Therapeutics, Teon Therapeutics Honoraria: Janssen Consulting or Advisory Role: Janssen Oncology, Teon Therapeutics, Fortis   Dr. Anthony Zietman: Leadership: Elsevier   Dr. Eric Klein:No relationships to disclose

Radiopharmaceuticals have experienced a resurgence over the past decade, with a series of approvals, billion-dollar deals and growing sales. On the latest BioCentury This Week podcast, Director of Biopharma Intelligence Karen Tkach Tuzman previews her upcoming analysis of the space, discussing the multidimensional nature of the technology's evolution, and the field's next-wave targets behind PSMA and SSTR2. BioCentury's editors also discuss the legacies of two U.S. lawmakers who won't stand for re-election, Reps. Anna Eshoo (D-Calif.) and Michael Burgess (R-Texas); the latest move by BioNTech to grow its global footprint; and the November rise in the XBI.Music for the 24th Bio€quity Europe promo produced by:Thomas de Paula Eby, Andreas Unge, Epidemic Sound via Getty Images

In this episode, join Dr. Geo as he converses with Dr. Mark Emberton, a leading figure in urology and a driving force behind transformative advances in prostate cancer diagnosis.With a focus on a landmark German study, Dr. Emberton shares insights on how PSMA and MRI imaging might soon render prostate biopsies a thing of the past. Our expert guest, an interventional oncologist, neurologist, and respected Dean of Medical Sciences at University College London, discusses the potential for these imaging techniques to provide definitive prostate cancer diagnoses without the need for invasive procedures.We'll get into the nitty-gritty of the study's results, which point to a future where a combination of PSMA and MRI scans could detect prostate cancer with astounding accuracy. Dr. Emberton examines the implications of this on the U.S. healthcare system and whether it can become the new gold standard for prostate cancer screening.In a candid comparison, Dr. Emberton contrasts the approach to prostate cancer in the U.K. with that in the U.S., offering listeners a global perspective on patient care and medical practice. This episode promises to be a deep dive into the frontiers of medical technology and a thought-provoking discussion on what lies ahead for men's health. Dr. Geo's conversation with Dr. Mark Emberton is an indispensable listen for anyone interested in the evolving landscape of cancer diagnosis and treatment.___________Dr. Mark Emberton's website - https://www.londonurologyspecialists.co.uk/team_member/professor-mark-emberton/___________Thank you to our sponsors.This episode is brought to you by AG1 (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, your nervous system, your immune system, your energy, recovery, focus, and, most things, aging. Enjoy AG1 (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 to 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 Store____________________________________DISCLAIMER: This audio is educational and does not constitute medical advice. This audio's content is my opinion and not that of my employer(s) or any affiliated company.Use of this information is at your own risk. Geovanni Espinosa, N.D., will not assume...

Dr. Rohan Garje reviews the latest rapid recommendation update for the ASCO guideline on systemic therapy in men with metastatic castration-resistant prostate cancer (mCRPC). He reviews what prompted the guideline update and the latest recommendation from the expert panel. Dr. Garje also discusses future updates to the guideline that are currently underway, and outstanding questions regarding systemic therapy for mCRPC. Read the latest update, “Systemic Therapy Update on 177Lutetium-PSMA-617 for Metastatic Castration-Resistant Prostate Cancer: ASCO Guideline Rapid Recommendation Update” at www.asco.org/genitourinary-cancer-guidelines. TRANSCRIPT This guideline, clinical tools, and resources are available at http://www.asco.org/genitourinary-cancer-guidelines. Read the full text of the guideline and review authors' disclosures of potential conflicts of interest disclosures in the Journal of Clinical Oncology, https://ascopubs.org/doi/10.1200/JCO.23.02128  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 Update on 177Lutetium-PSMA-617 for Metastatic Castration-Resistant Prostate Cancer: ASCO Guideline Rapid Recommendation Update.  Thank you for being here today, Dr. Garje. Dr. Rohan Garje: Thank you so much for having me, Brittany. Brittany Harvey: And then, just before we discuss this guideline, I'd like to note that ASCO takes great care in the development of its guidelines in 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 on this episode today, are available online with the publication of the update in the Journal of Clinical Oncology, which is linked in the show notes.  So then, to dive into the content of this rapid update, first, Dr. Garje, what prompted this rapid update to the guideline on Systemic Therapy for Metastatic Castration Resistant Prostate Cancer? Dr. Rohan Garje: So, last year, when we did a rapid update on ASCO prostate cancer guidelines, we recommended the addition of 177Lutetium-PSMA-617, also called as PLUVICTO, as a treatment choice for patients who have PSMA-positive metastatic castrate-resistant prostate cancer. After that approval, the primary imaging modality at the time of this initial drug approval was based on gallium-68, which was used in that clinical trial, which was VISION. Since then, we have access to a couple of new radiotracers, one of them being piflufolastat, also called as PYLARIFY, and the newer one called flotuflastat F-18, which is also called as POSLUMA, as additional imaging agents to detect PSMA-positive lesions. So, our expert panel group, along with my co-chairs, we thought to add these additional choices for patient selection because this provides the treating physicians additional options because there really are nuances involved in these imaging agents. So this helps broaden the access to  177Lutetium-PSMA-617 for patients. Brittany Harvey: Excellent. I appreciate you providing that background that the panel was reviewing.   So then, based on this updated information, what is the updated recommendation from the expert panel? Dr. Rohan Garje: So, for the new recommendation, the guideline expert panel recommends use of one of these three radio tracers, that is Ga-68PSMA-11, or piflufolastat F-18, or flotufolastat F-18 as one of the radiotracer choices to screen for PSMA-positive lesions on a PSMA scan, and potentially select the patients for PSMA 177lutetium. This way, we can use one of these three agents rather than previously recommended, as per FDA approval of gallium 68. Now, the reason behind these additional agents, as I was just alluding in my initial comment, is each institution may have access to one of these agents. For example, if a patient had a testing done by piflofolastat or flotufolastat, if they are PSMA-positive, it has shown PSMA-positive lesions as per VISION criteria, we do not suggest the patients to undergo gallium-68 assisted imaging again to have selection for PSMA lutetium therapy. This is unnecessary imaging. We have evidence now, based on the studies which were done with PYLARIFY, which is the piflofolastat, or the flotufolastat, which is POSLUMA, that they are equally good in detecting PSMA-positive lesions. This way we can avoid additional imagings for patients who are being screened for lutetium therapy. Brittany Harvey: Understood. Thank you for reviewing the expansion of this recommendation to avoid additional or unnecessary screening.  So then, Dr. Garje, the article mentions complete updates to the metastatic castration-resistant prostate cancer guideline are underway. At a high level, could you review what new evidence the panel will look at to update their evidence-based recommendations? Dr. Rohan Garje: There have been a lot of developments in the last year, at least, in the treatment strategies for patients with metastatic castration-resistant prostate cancer. Earlier this year, we have seen three big updates about the first-line metastatic CRPC setting, where the combination of PARP inhibitors and androgen receptor pathway inhibitors were tested. For example, in the TALAPRO-2 study talazoparib and enzalutamide, and in the MAGNITUDE study, it was niraparib along with abiraterone. And in the PROpel study, the combination of olaparib and abiraterone was studied. Now, all these combinations have recently received FDA approval with specific nuances with regards to folks who have biomarker positive disease, specifically BRCA1 and BRCA2 mutations. So it is very important to refine this information so that it is utilized by practicing oncologists so that it is widely adapted in their day to day practice. Now, in addition, we also are focusing on addressing the need for utilizing biomarkers. The biggest thing for us to offer a biomarker driven therapy is to do biomarker testing. So we are focusing on making sure patients with advanced prostate cancer get biomarker testing so that we can identify who are the patients who get selected. So this particular guideline update is addressing those needs.  And then most recently at the recent ESMO meeting, we also noted the positive data from a study called PSMAfore, which evaluated PSMA 177lutetium prior to chemotherapy. This study showed positive data based on progression free survival benefit. So we will review additional data from that and see if a guideline update can be done based on this. So it is very exciting. Now, obviously, we are also waiting on survival data on all the studies. So we are closely monitoring all the updates on these studies so that we can provide more rational guidance based on not only progression-free survival benefit in a specific cohort and also to see if it helps with overall survival improvement. Brittany Harvey: Absolutely. We'll look forward to the panel's review of this evidence and then future updates to this full guideline.  So then, finally, Dr. Garje, you've alluded to awaiting some data. So could you expand on what are some of the outstanding questions regarding systemic therapy for metastatic castration-resistant prostate cancer? Dr. Rohan Garje: I would put that in two boxes. Number one, sequencing. So we are excited that we have a broad spectrum of options; androgen receptor pathway inhibitors, chemotherapy options, radium-223. We have lutetium based options and then biomarker selected patients with PARP inhibitor combinations and select patients with benefit for checkpoint inhibitors. Now, the biggest question we need to answer is how to sequence them, which drug or which combination strategy is ideal for one particular patient. Now, obviously, when we do not have clinical trials which have addressed sequencing, we as an expert panel would want to come up with some mechanism of consensus to identify what treatment sequence would work best for patients. So that is an important question this guideline panel wants to address where we can give some generic information as a consensus, based on the experience of the panel to give guidance for practicing physicians the best sequencing.  Now, second thing, very equally important, is biomarkers. This particular guideline update is also focusing on making sure biomarker testing is universal. There has been a lot of evidence that biomarker testing happens very late in the course of the disease, which precludes a lot of patients from these combination strategies. So this particular guideline also is focusing on what biomarkers to be tested and at what time frame, so that they can be optimally utilized for the patient treatment so that the patients will have the best cancer outcomes. Brittany Harvey: Definitely, those are important questions for personalized care for people with prostate cancer.   I want to thank you so much for your work on this rapid update and your ongoing work on the updates to the full guideline, Dr. Garje, and thank you for your time today. Dr. Rohan Garje: Sure, thank you so much. Brittany Harvey: And thank you to all of our listeners for tuning in to the ASCO Guidelines podcast. To read the full guideline update, 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.  

Enzalutamide and 177Lu-PSMA-617 in poor-risk, metastatic, castration-resistant prostate cancer (mCRPC): A randomised, phase II trial: ENZA-p (ANZUP 1901)

This week on BackTable Urology, Dr. Aditya Bagrodia (UCSD), medical oncologist Dr. Rana McKay (UCSD) and radiation oncologist Dr. Shankar Siva (University of Melbourne) discuss the growing role of radiation therapy in kidney cancer treatment. --- SHOW NOTES Shankar first explains the original historical studies that provided evidence of the limited efficacy of low dose conventional radiation therapy (RT) in treating kidney cancer. However, he and Rana discuss how stereotactic body radiation therapy (SBRT), a newer technology which delivers a higher dose per fraction more accurately, has shown better outcomes in clinical trials than conventional RT. They also explain the associated risks with SBRT and how neoadjuvant therapies can be combined with radiation. They also consider the use of SBRT in bulky tumors and those with IVC thrombus. All three doctors agree that radiation therapy needs to be incorporated into a multimodal approach to kidney cancer. They also discuss the potential of radiation therapy in the cytoreductive setting and its role in delaying systemic therapy in patients with oligometastases. Finally, they explore the possibility of using PET imaging to detect oligometastatic disease. Although prostate-specific membrane antigen positron emission tomography (PSMA PET/CT) imaging is mostly used to stage prostate cancer, other solid tumors like renal cell carcinoma (RCC) may also express PSMA. For this reason, they agree that a next generation PSMA PET/CT equivalent for RCC could be revolutionary. Lastly, they predict what the future of RCC could hold by examining newer therapies, such as radioligand therapy and cyberknife. --- RESOURCES Kidney Cancer Association: 2023 International Kidney Cancer Symposium (Nov. 9-11) https://www.kidneycancer.org/ikcs/2023-ikcs-north-america/ Decipher by Veracyte https://decipherbio.com/ WellPrept https://wellprept.com/

Q&A review of nuclear medicine therapies with Lu177 PSMA and Ra223 Dichloride for prostate cancer for board exams.  Check out the free downloadable study guide at www.theradiologyreview.com. Prepare to succeed!

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.

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