Podcasts about genitourinary cancers symposium

In this episode of MedNews Week's Oncology Unplugged, host Chandler Park, MD, a medical oncologist at Norton Cancer Institute in Louisville, Kentucky, spoke with Petros Grivas, MD, PhD, clinical director of the Genitourinary Cancers Program at Fred Hutchinson Cancer Center and a professor of medicine at the University of Washington School of Medicine, about key updates from the 2025 Genitourinary Cancers Symposium and the evolving treatment paradigm for muscle-invasive bladder cancer (MIBC).

Drs Terence Friedlander, Matthew D Galsky, Neeraj Agarwal, Andrew J Armstrong and Elisabeth I Heath discuss recent updates on available and novel treatment strategies for bladder cancer and prostate cancer. CME information and select publications here.

Featuring perspectives from Dr Terence Friedlander and Dr Matthew D Galsky, Dr Neeraj Agarwal and Dr Andrew J Armstrong, moderated by Dr Elisabeth I Heath, including the following topics: Introduction (0:00) Role of Antibody-Drug Conjugates (ADCs) in Front-Line Therapy for Metastatic Urothelial Bladder Cancer (mUBC) — Dr Friedlander (2:53) Evidence-Based Use of ADCs for Relapsed/Refractory mUBC — Dr Galsky (33:04) Evolving Role of Treatment Intensification with Androgen Receptor Pathway Inhibitors for Nonmetastatic and Metastatic Prostate Cancer — Dr Armstrong (1:01:28) Optimal Integration of PARP Inhibitors into Therapy for Prostate Cancer — Dr Agarwal (1:27:49) CME information and select publications

Drs Terence Friedlander, Matthew D Galsky, Neeraj Agarwal, Andrew J Armstrong and Elisabeth I Heath discuss recent updates on available and novel treatment strategies for bladder cancer and prostate cancer. CME information and select publications here.

In this episode of Oncology Unplugged, a podcast series from OncLive and MedNews Week, podcast host Chandler Park, MD, a medical oncologist at Norton Cancer Institute in Louisville, Kentucky, was joined by Petros Grivas, MD, PhD; and Ruben Raychaudhuri, MD, to talk about a pilot trial investigating neoadjuvant accelerated methotrexate, vinblastine,doxorubicin, and cisplatin (aMVAC) plus pembrolizumab (Keytruda) in patients with non-urothelial muscle-invasive bladder cancer, findings from which were presented at the 2025 Genitourinary Cancers Symposium. Dr Grivas is clinical director of the Genitourinary Cancers Program and a professor in the Clinical Research Division at Fred Hutchinson Cancer Center, as well as a professor in the Division of Hematology and Oncology at the University of Washington School of Medicine in Seattle. Dr Raychaudhuri is an assistant professor in the Clinical Research Division at Fred Hutchinson Cancer Center, as well as an assistant professor in the Division of Hematology and Oncology at the University of Washington School of Medicine. In their exclusive conversation, Drs Park, Grivas, and Raychaudhuri discussed key efficacy and safety findings from this study; the need for conducting dedicated research in bladder cancer patient populations with variant histologies; and the potential of biomarkers, such as HER2 expression, to improve the bladder cancer treatment paradigm in the future.

Featuring an interview with Dr Emmanuel S Antonarakis, including the following topics: Perspectives on advances in the management of prostate cancer over the last decade (0:00) Nonmetastatic high-risk prostate cancer and androgen deprivation therapy (ADT) intensification with abiraterone: Insights from the STAMPEDE trial (7:39) EMBARK: A Phase III trial of enzalutamide or placebo with leuprolide acetate and enzalutamide monotherapy for high-risk biochemically recurrent prostate cancer (15:25) Quality of life and preservation of sexual function with enzalutamide monotherapy compared to ADT alone or enzalutamide with ADT (20:20) Management of locally advanced prostate cancer with and without biochemical recurrence (23:58) PRESTO trial of ADT intensification with apalutamide with or without abiraterone for high-risk biochemically relapsed prostate cancer (30:35) CDK4/6 inhibitors, proteolysis-targeting chimeras and other novel therapeutic approaches for targeting androgen receptor signaling in prostate cancer (31:41) Choice of endocrine partner with ADT and incorporation of docetaxel in the treatment of metastatic hormone-sensitive prostate cancer (35:38) Other potential novel therapeutic strategies for prostate cancer (42:28) Integration of genomic testing for patients with prostate cancer; PARP inhibitor combinations for the treatment of metastatic castration-resistant prostate cancer (mCRPC) (43:57) Incorporation of radiopharmaceuticals (ie, lutetium Lu 177 vipivotide tetraxetan, radium-223) into the management of prostate cancer (52:49) Perspectives on the results of the Phase III CONTACT-02 trial evaluating cabozantinib in combination with atezolizumab for mCRPC (57:44) CME information and select publications  

Dr Emmanuel Antonarakis from the University of Minnesota in Minneapolis reviews research findings presented at the 2024 Genitourinary Cancers Symposium and provides his perspectives on current and novel treatment approaches for prostate cancer.

Dr Emmanuel Antonarakis from the University of Minnesota in Minneapolis reviews research findings presented at the 2024 Genitourinary Cancers Symposium and provides his perspectives on current and novel treatment approaches for prostate cancer, moderated by Dr Neil Love. Produced by Research To Practice. CME information and select publications here (https://www.researchtopractice.com/ASCOGU24/Review/Prostate).

It's been a busy few weeks here at CURE® and in the oncology space as a whole, as the last two weekends had back-to-back meetings: the American Society of Clinical Oncology's Gastrointestinal Cancers Symposium, and then their Genitourinary Cancers Symposium.  Here are some highlights from the conference, but as always, you can find all of our coverage at curetoday.com.  Gastrointestinal Cancers Symposium  Imfinzi, Avastin, TACE May ‘Set a New Standard of Care' in Liver Cancer For patients with liver cancer whose disease is not eligible to be removed via surgery, adding Imfinzi and Avastin to transarterial chemoembolization — also known as TACE — tended to lengthen the time patients lived before their disease got worse, according to findings from the EMRALD-1 trial. These improvements in progression-free survival over TACE alone could lead to a new standard of care for this patient population, according to the lead study author, Dr. Riccardo Lencioni.  More specifically, patients who received Imfinzi and Avastin plus TACE lived for a median of 15 months before death or disease worsening, compared to 8.2 months for patients who received TACE alone. This correlates to a 23% reduction in the risk of disease progression or death, and benefits were seen across different patient subgroups.  Notably, the researchers on EMRALD-1 are still monitoring how the addition of the two drugs impacts overall survival. Once those data become more clear, it is possible that the drug manufacturers could submit this regimen to the FDA for approval, thereby officially shaking up the standard of care of TACE, which has remained the main treatment in this setting for about two decades.  Cancer in Bloodstream May Predict CRC Outcomes Circulating tumor DNA — also known as ctDNA — was another hot topic at the Gastrointestinal Cancers Symposium. So ctDNA measures little fragments of cancer that are found in the bloodstream after cancer treatment.  Now, findings from the BESPOKE trial highlight the fact that ctDNA may offer insight into the recurrence risk in patients with stage 2/3 colorectal cancer who underwent surgery and then chemotherapy. The researchers used ctDNA to help determine minimal residual disease, or MRD, status. Essentially, patients with disease still detected in the blood stream were MRD positive, while those without detectable cancer were MRD negative. Findings showed that those with MRD negativity tended to live longer without experiencing relapse or death compared to patients with MRD positivity.  Genitourinary Cancers Symposium Survival Benefits with Keytruda and Padcev in Advanced Urothelial Cancer Back in December, the Food and Drug Administration approved Padcev plus Keytruda for patients with previously treated locally advanced or metastatic bladder cancer. The approval was based on primary findings from the EV-302 trial. Now, updated findings from that trial are showing that the drug duo continues to outperform chemotherapy when it comes to progression-free survival — that's the time patients live before their disease gets worse — as well as overall survival, which is the time patients live before death of any cause.  Notably, these survival benefits were seen across patient subgroups, such as those with visceral metastases and lymph node-only disease. According to the lead study author, Dr. Michiel S. Van Der Heijden, this could result in a new standard of care in patients with locally advanced or metastatic urothelial carcinoma.  Many Patients Miss Out on Testing to Guide Prostate Cancer Treatment On the prostate cancer front, a study found that many people with metastatic castration-resistant prostate cancer are not undergoing germline or somatic testing. Now this is really important because back in 2020, two PARP inhibitors were approved in this setting. These are targeted drugs approved for patients whose cancers have certain characteristics, which can be determined by these types of tests.  Rates of germline and somatic testing have increased since the FDA approvals, but according to the study — which looked at real-world evidence of patients being treated in community cancer and urology centers — about 40% of patients did not undergo standard-of-care testing.  Study author, Dr. Neal Shore, said that this indicates the need for improved education on the importance of germline and somatic testing.  For more news on cancer updates, research and education, don't forget to subscribe to CURE®'s newsletters here. 

Last week, we saw some big headlines in the oncology space, from Dexter Scott King's death from prostate cancer and MLB Hall-of-Famer Ryne Sandberg announcing that he was diagnosed with the disease.  The FDA also requested a label update for CAR-T cell therapies that would warn patients and providers about secondary malignancies that have been reported from the treatment. Also, we took a look at laughter therapy, and how it could help patients and caregivers.  We've also been busy covering two conferences — ASCO's Gastrointestinal Cancers Symposium, as well as their Genitourinary Cancers Symposium, so tune in later this week for a special podcast episode highlighting some major research from those events.  Dexter Scott King Dies of Prostate Cancer, Ryne Sandberg Diagnosed With the Disease Last Monday, Jan. 22, we saw two big stories in the prostate cancer space. First, Dexter Scott King, the son of the Civil Rights activist, Martin Luther King, Jr., died of prostate cancer. He was 62 years old.  At the time of his death, King was the Chairman of the King Center, which is an organization focused on educating the world about the life and legacy of Dr. Martin Luther King Jr. Dexter Scott King was also the president of the King estate.  In a statement announcing King's death, his wife, Leah Weber said, “He transitioned peacefully in his sleep at home with me in Malibu. He gave it everything and battled this terrible disease until the end.”  And on the same day Dexter Scott King died, Major League Baseball Hall-of-Famer, Ryne Sandberg, announced that he was diagnosed with metastatic prostate cancer.  The 64-year-old — who was a 10-time All Star during his tenure for the Chicago Cubs, which ran from 1982 to 1997 — announced his diagnosis on Instagram. He said that received the diagnosis a week earlier and has started treatment. He asked that fans keep him in their thoughts and prayers.  FDA Requests Warnings on CAR-T Cell Therapies, Citing Secondary Cancers The investigation into CAR-T cell therapies continues. Recently, the Food and Drug Administration (FDA) requested that approved BCMA- or CD19-targeted CAR-T cell therapies update their labeling to include a warning of reports of T-cell malignancies, including CAR-positive lymphomas, which have been reported in patients who use this type of therapy.  Back in November, the FDA announced that it was investigating reports of secondary diseases in patients who underwent CAR-T cell therapy. The available data shows that these diseases are extremely rare, and researchers are still looking into what, exactly, is causing them.  Now, the FDA wrote letters to the manufacturers of five CAR-T cell therapies, requesting that they include a Boxed Warning — which is the highest safety-related warning for drugs — outlining the potential risks of CAR-T cell products. The companies must respond to the FDA within 30 days of receiving the letters, which were sent out on Jan. 19.  Laughter Therapy May Improve Mood, Decrease Pain in Patients With Cancer And on a much lighter note, we covered recent research showing that laughter therapy can decrease mood disturbances in patients receiving palliative care for late-stage cancer, as well as their loved ones. The findings, which were published in the journal, Cancer Nursing, also found that the laughter therapy reduced pain perception in patients and decreased levels of burnout in caregivers.  Laughter therapy refers to alternative and complementary therapy using humor to help relieve stress and pain, in addition to potentially improving a patient's sense of well-being, according to the National Cancer Institute. In this instance, it consisted of five 20- to 30-minute sessions held over five consecutive days. The participants introduced themselves using funny tools to relieve tension, and moved their bodies in laughing rhythms.  “This indicates that our palliative care patients and family caregivers would have a positive view of the use of laughter or humor in their palliative circumstances,” the researchers wrote.   For more news on cancer updates, research and education, don't forget to subscribe to CURE®'s newsletters here.

On this week's episode, we're continuing our coverage of data presented at the 2023 ASCO Genitourinary Cancers Symposium in San Francisco. Daniel Petrylak, MD, and Matt Galsky, MD, discuss two separate studies in urothelial carcinoma. Following this, in recognition of International Women's Day, we'll hear from Isabel Rubio, MD, PhD, President of the European Society of Surgical Oncology. Dr. Rubio shares some of the efforts being made by the Society to help encourage women to pursue a career in surgical oncology as well as leadership roles in oncology.To listen to more podcasts from ASCO, visit asco.org/podcasts.

On this episode, we're continuing our coverage of data presented at the 2023 ASCO Genitourinary Cancers Symposium, which took place recently in San Francisco. We'll hear from three researchers about their findings in prostate cancer trials reported at the meeting.To listen to more podcasts from ASCO, visit asco.org/podcasts.

On this episode, we're sharing news from our coverage of data presented at the 2023 ASCO Genitourinary Cancers Symposium, which took place recently in San Francisco. We'll hear from two researchers about their findings in renal cell carcinoma (RCC).To listen to more podcasts from ASCO, visit asco.org/podcasts.

ASCO: 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 the Research Round Up series, members of the Cancer.Net Editorial Board discuss the most exciting and practice-changing research in their field and explain what it means for people with cancer. In today's episode, 4 Cancer.Net Specialty Editors discuss new research in prostate, bladder, kidney, and testicular cancers presented at the 2022 Genitourinary Cancers Symposium and 2022 ASCO Annual Meeting. This episode has been adapted from the recording of a live Cancer.Net webinar held June 15th, 2022, led by Dr. Neeraj Agarwal, Dr. Timothy Gilligan, Dr. Petros Grivas, and Dr. Tian Zhang. Dr. Agarwal directs the Genitourinary Oncology Program at the Huntsman Cancer Institute at the University of Utah. Dr. Gilligan is an Associate Professor and Medical Oncologist at the Cleveland Clinic Taussig (TOSS-ig) Cancer Center. Dr. Grivas is the clinical director of the Genitourinary Cancers Program at University of Washington Medicine. He is also an associate member of the clinical research division at the Fred Hutchinson Cancer Research Center. 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. Full disclosures for Dr. Agarwal, Dr. Gilligan, Dr. Grivas, and Dr. Zhang are available at Cancer.Net. Greg Guthrie: Good afternoon, everyone. I'm Greg Guthrie, and I'm a member of the Cancer.Net content team. I'll be your host for today's Research Round Up webinar focusing on cancers of the genitourinary tract. Cancer.Net is the patient information website of the American Society of Clinical Oncology, known as ASCO. So today, we'll be addressing research from 2 2022 scientific meetings, the ASCO Annual Meeting held in Chicago in June and the Genitourinary Cancers Symposium held in San Francisco in February. Our participants today are all Specialty Editors of the Cancer.Net Editorial Board, and they are Dr. Neeraj Agarwal of the Huntsman Cancer Institute in University of Utah, Dr. Timothy Gilligan of the Cleveland Clinic Taussig Cancer Center, Dr. Petros Grivas of the Fred Hutchinson Cancer Research Center and University of Washington, and Dr. Tian Zhang of the University of Texas Southwestern Medical Center. Thank you, everyone, for joining us today. So starting us off today is Dr. Agarwal who will be talking about research in prostate cancer. Go ahead, Dr. Agarwal. Dr. Agarwal: Hi. Thank you, Greg. So I'd like to start with 2 studies. They both are in prostate cancer which will be followed by my colleagues presenting studies in other cancers in bladder cancer and kidney cancer. So I'll start with this abstract, which was highly discussed by the doctors at the ASCO Annual Meeting a few weeks ago, and it has a lot of relevance in our practice. So this is abstract #5000 presented by Dr. Michael Hofman, and this was the update on a clinical trial which compared lutetium PSMA-617, or lutetium PSMA, to put it simply, with cabazitaxel in patients with metastatic castration-resistant prostate cancer who had disease progression after receiving docetaxel chemotherapy. So, who were the patients who were enrolled on the study? These patients had, as I said, metastatic castration-resistant prostate cancer, who had disease progression after docetaxel chemotherapy, and who had to have high PSMA-expressing prostate cancer. And the way they assessed the presence of high PSMA expression was by using a specialized kind of PET scan known as Gallium 68 PSMA-11 PET scan. In addition, they made sure that these patients do not have another type of prostate cancer, also call it dedifferentiated prostate cancer, by making sure that those patients did not have a traditional PET scan-positive disease. So this was a highly selected patient population who were expressing PSMA on their prostate cancer. Prior to this presentation, the earlier presentation had shown that lutetium PSMA was superior to cabazitaxel as far as progression-free survival is concerned and also was associated with lower incidence of grade 3 or 4 side effects. In this update, after a longer follow-up of 3 years, Dr. Hofman and Dr. Davis, who is a senior author, they presented the data on overall survival, which was a secondary analysis, and overall survival was similar with cabazitaxel as well as lutetium PSMA in the range of 19 months. We did not see any new safety signal. So, what does it mean for us? What does this mean for our patients? My key takeaway message here is, lutetium PSMA is a suitable option for men with metastatic castrate-resistant prostate cancer who are expressing high PSMA on their prostate cancer after they had sustained disease progression after docetaxel. However, cabazitaxel is also a valid option in this setting. I would like to add my own view in addition to this because lutetium PSMA was better tolerated and was also associated with better progression-free survival. In my patients who are progressing on docetaxel chemotherapy, I would like to use lutetium PSMA first followed by cabazitaxel chemotherapy. So that would be my key takeaway from this abstract. Now we can move to the next abstract. This was also an update, a much longer update, on ENZAMET trial. If you recall, ENZAMET trial was one of those trials which established that deeper androgen blockade, or deeper androgen signaling inhibitors such as enzalutamide, apalutamide, or abiraterone, these trials were conducted in 2015 onwards, and all these trials showed that upfront using deeper androgen signaling inhibitors at the time of metastatic hormone-sensitive prostate cancer onset improved survival. So ENZAMET trial used enzalutamide, and it showed in the first analysis, which was presented by Dr. Davis and Dr. Sweeney in the 2019 ASCO Meeting Plenary session, that adding enzalutamide to androgen-deprivation therapy in patients with metastatic hormone-sensitive prostate cancer significantly improved survival. In this longer follow-up of 68 months, so we are talking about almost 6 years of follow-up, now, these investigators from ENZAMET trial, as presented by Dr. Davis, showed that the combination of enzalutamide with androgen deprivation therapy or testosterone suppression therapy continues to significantly improve survival in patients with newly diagnosed hormone-sensitive prostate cancer or metastatic prostate cancer. One interesting part of this unique aspect of this trial was that patients were allowed to receive docetaxel chemotherapy concurrently to the protocol treatment. And in this trial, 45% patients actually receive docetaxel chemotherapy. So 503 patients exactly out of 1,000-plus patients. So if you look at the subgroup analysis of those patients who received docetaxel chemotherapy, enzalutamide does not seem to benefit those patients from the overall survival perspective. So on the face of it, it looks like enzalutamide is not helping those patients who are receiving docetaxel concurrently. But there are some caveats with that kind of subgroup analysis. The first one is this is not a randomized assignment of docetaxel chemotherapy. Patients were determined to have docetaxel chemotherapy after discussion with their respective oncologist. This was not a prespecified analysis that so many patients with docetaxel will receive enzalutamide. Also, this was not a randomized assignment of docetaxel. And third, that I don't think this trial had enough power to look for that subgroup analysis. So my take on this trial is that updated results from this trial, almost 6 years of follow-up now show that enzalutamide continues to improve overall survival with a 30% reduction in risk of death in patients with metastatic castration-sensitive or hormone-sensitive prostate cancer. Furthermore, the effect of enzalutamide, in my view, on overall survival is independent of the receipt of docetaxel. If you look at the whole trial population for which the trial was covered for, enzalutamide improved survival for all patients. And based on these results, I feel more confident in saying that upfront intensification of treatment with deeper androgen inhibition remains a standard of care for our patients with metastatic hormone-sensitive prostate cancer and should be offered to all eligible patients with this condition. With that, I would like to wrap up the prostate cancer abstracts. Thank you very much. Greg Guthrie: And thank you, Dr. Agarwal. Next up, we will have Dr. Gilligan, who is going to be discussing testicular cancer. Dr. Gilligan: Thank you very much. So I have 2 studies I want to talk about and then just give a headline of some interesting things that I think are kind of coming down the road. Both of these abstracts have to do with improvement over time in specific patient populations we used to worry about. I'm not saying we don't worry about them anymore, but things are looking better now than they had 1 or 2 decades ago. So the first topic addresses late relapses in testicular cancer. And historically, we have been concerned that these patients did worse and had worse outcomes. And late relapse could variously be described as after 2 years or after 5 years. In the current study, they defined late relapse as being after 2 years and very late relapse as being after 5 years. And what was special about the study was that it captured the entire population of patients with testis cancer in Norway and Sweden so that it wasn't based on a center of excellence that gets selective referrals. It was actually a population-based study. And the key conclusion of the study was one I found, once again, that late relapses are rare. So for stage I patients, 2% of patients will relapse after 2 years, 1% after 5 years, and 0.5%, so 5 out of 1,000 patients, after 10 years. So if you're 2 years out, the likelihood of a relapse is quite low. And if you're 5 years out, it's half of that. In patients with metastatic disease, similarly, 3.6% relapse after 2 years, 1.6% after 5, and 0.8% after 10 years. And what was interesting to me was that if you looked at the more recent patients who were diagnosed after 1995 - I know that doesn't sound very recent, but they had even earlier patients also in the study - the very late relapse rate almost resolved and went away. It went from 2.2% all the way down to 0.8%. So I think with modern imaging, modern care patterns, we're seeing less of this than we used to. But overall, patients were doing better even if they do relapse late. One thing that was interesting in the study to me also was for stage I disease, we typically recommend surveillance rather than active treatment. So active treatment with non-seminomas would be a retroperitoneal lymph node dissection or more surgery or chemotherapy. With seminoma, it would usually be chemotherapy or radiation, although surgery is being investigated there now. And they did find that in men who chose surveillance, which we still recommend, the late relapse rate was a little bit higher, but it was still affecting a small percent of patients. So the relapse rate beyond 2 years was 4% rather than 1%, but out of 4,000 patients, there were only 3 deaths from late relapse. So this isn't changing the recommendation for surveillance, but it is an alert that patients who are on surveillance for stage I disease have a slightly higher risk of late relapse and that may affect how we follow them and specifically how long we follow them. One of the things that was interesting in the study is in the United States, we often stop scans at 5 years, but in the SWENOTECA countries, they continue scans all the way out to 10 years. I don't know that U.S. guidelines are going to change, but it was a provocative finding. The key thing, as I alluded to at the beginning, was that 61% of patients with late relapse were alive 10 years later, and while we would like that number to be higher, it used to be around 50% in older studies. So it's a significant improvement from where we were before. A particularly interesting thing to me was that patients relapsing 2 to 5 years out actually had the best prognosis. Patients who relapsed in years 1 to 2 had a worse prognosis and patients relapsing after 5 years had a worse prognosis, whereas the patients relapsing 2 to 5 years had a better prognosis. In the end, I think what this means for us is that patients are doing better. It's not going to really change our treatment patterns, but it's reassuring that we shouldn't be pessimistic about late relapses, and we still have a solid chance of curing them. So again, bottom line, most men with late relapse is cured and late relapse is less common now than it was earlier, particularly in non-seminomas. Let's go to the next study. So this is a different group of patients who had a particularly ominous prognosis historically and still we have a lot of room for improvement. These are patients with non-seminomas that start in the mediastinum. So in the chest, under the breastbone, under the sternum typically. And patients are treated aggressively upfront, they are considered poor risk at the initial time of diagnosis, and they're treated aggressively at the time with 4 cycles of BEP or 4 cycles of VIP chemotherapy. And then they go for surgery to remove any residual disease. And the hope is they're cured at that point because historically, if there was a relapse after chemotherapy and surgery, it was almost impossible to cure them. Indiana University published their results using high-dose chemotherapy in this population, and they reported that 30% of men who were treated with high-dose chemotherapy had no evidence of cancer after 2 years, and 35% were still alive. Obviously, we need longer follow-up, but most of the relapses you're going to see are going to be in the first 2 years. So while again, there is significant room for improvement here, this indicates that high-dose chemotherapy is a good option, and that has been a question. So this is reassuring in that regard. But it is a good option for men with relapsed mediastinal non-seminomas of the germ cell tumors. So there's hope there where in the past, this has felt a little bit helpless. The thing I wanted to also highlight was that there are 3 things I think are going to be interesting to keep an eye on over the next year. One is the use of surgery for early-stage seminomas. There are a number of papers out about that. I still think this is an investigational approach, and so I didn't want to go into great detail about it, but it is looking like that RPLND, or retroperitoneal lymph node dissection, will likely or may be an option for stage I and stage II seminoma in the future. We are getting more evidence for that. It's not quite as promising as we had hoped until there's more data that's needed, but it's looking like that will become an option. So for men with early-stage seminoma, at least raising the question whether surgery is an alternative to chemotherapy or radiation, is an important discussion to have with your oncologist. Secondly, MRI rather than CT scans for surveillance. So to keep an eye on men who have been treated or men who are just stage I and are being followed and typically come in routinely for CT scans, which expose people to ionizing radiation, which theoretically has a risk of causing cancer, there's more and more data that MRI is just as good as CT, and MRI does not use ionizing radiation. So there's probably going to be an expanding role for MRI as an alternative to CT scans. And lastly, the use of microRNA rather than just depending on serum tumor markers. So right now, we use the blood tests alpha-fetoprotein, beta hCG, extensively to monitor for relapse, and there's more and more evidence for using what we call microRNAs instead. It may be more accurate in multiple different settings. So it'll be interesting to see how that evolves and that's what I wanted to cover today. Thank you very much. Greg Guthrie: Thank you, Dr. Gilligan. And now we have Dr. Grivas, who's going to discuss some research in bladder cancer. Dr. Grivas: Thank you so much, Greg, and thanks Cancer.Net for the great opportunity to discuss this for our patients. We're very excited about the data from the ASCO Annual Meeting, and I would encourage the audience to review as possible other presentations as well. I'm going to cover 3 highlights. I'm going to start with the QUILT-3.032 study. This trial reported the final results of a clinical trial that took place in different centers and involved patients with what we used to call “superficial bladder cancer.” And the modern term is “non-muscle-invasive bladder cancer.” Bladder cancer that does not involve the muscle layers, not that deep in the bladder wall. Non-muscle-invasive bladder cancer is usually treated by our colleagues in urology with installation inside the bladder with an older form of immunotherapy which is BCG. And that's the most common way we treat this disease. And proportion of patients may have tumors that may not respond to BCG that may come back or persist despite the installation of the BCG in the bladder. And these patients usually have a standard of care of getting what we call radical cystectomy, meaning, removal of the bladder and the lymph nodes around the bladder, radical cystectomy and lymph node dissection. However, many patients may not have, I would say, the opportunity to get the surgery because the body may not be that strong to undergo that significant procedure. Very few patients may have that challenge because of other medical conditions or what we call poor performance status. Or some patients for quality-of-life reasons may try to keep their bladder as long as possible. And for some of those patients, that might be an option. And we have been looking for those options in the last few years. Intravesical, inside the bladder, installations of chemotherapy have been used with some positive results in some other studies. So that's an opportunity. We call this intravesical, inside the bladder, installations of chemotherapy, and the other option is an FDA-approved agent given intravenously inside the vein called pembrolizumab, which is in the form of immunotherapy. Of course, research continues. And this study I'm showing here from Dr. Chamie and colleagues, looked at this combination of BCG plus this molecule called N-803. This is another form of immunotherapy, and this was tested in patients who have this BCG-unresponsive, as we called it, non-muscle-invasive bladder cancer. The results were very promising. I would say impressive that it was a high response rate if we focus our attention on patients who had the superficial form carcinoma in situ, about 70% had no evidence of cancer upon further evaluation of the bladder. And in many of those patients that this response lasted for more than 2 years. 96% of patients avoided to have worsening of the bladder cancer in 2 years for those who had a response, and about 9 out of 10 avoided cystectomy again from those patients who had received the response. So it was 70% of all the population. And as you see, all patients, 100% were alive without dying from bladder cancer after 2 years, which again is a very promising finding. This combination, to conclude, this inside the bladder installations of BCG plus the N-803, looks very promising. For those patients with BCG-unresponsive non-muscle-invasive bladder cancer, that might be an option down the road, we have to see. Now I'm going to shift my attention to patients with metastatic or spread urothelial cancer. I want to point out that I'm a co-author in this abstract and I participated in that survey I will show you the results from. This is a population of patients who have spread cancer from the urinary tract, either the bladder was the most common origin or other parts of the urinary tract, for example, what we call kidney, pelvis and ureter, or rarely the urethra. The urothelial cancer that starts from those areas, again more commonly bladder, if it spreads, if it goes outside the urinary tract system, usually those patients get chemotherapy, what we call with an agent called cisplatin if they can tolerate that chemotherapy drug or carboplatin if they cannot tolerate the cisplatin drug. And usually either of these, cisplatin or carboplatin, is combined with a drug called gemcitabine. That's the most common chemotherapy used as initial therapy for patients with spread metastatic urothelial cancer. In this abstract, Dr. Gupta and colleagues tried to survey 60 medical oncologists, including myself, who treat urothelial cancer that considered experts in this disease type, to see if there are any features that could deter us from using chemotherapy in those patients. In other words, are there any features that may make us think that chemotherapy may be too risky for our patients and we should not do it? We should give immunotherapy instead. This is probably a small proportion of our patients, maybe 10 to 20% in our practice, may not be able tolerate that chemotherapy. And which are those features? Poor performance status, meaning the body is very tired and the patient is not moving too much, is confined in the chair or the bed most of the day, and rely on others on daily activities. This is what defines the performance status of ECOG 3. Peripheral neuropathy, meaning that there is numbness or tingling or weakness in the hands or the feet that impact the quality of life. And patients may have trouble buttoning buttons or tying laces, so impacting the quality of life. That's grade 2 neuropathy. Symptomatic severe heart failure, there is a grading system, like New York Heart Association Class III or IV that is significant, notable heart failure symptoms. And also, patients with kidney failure with what we call creatinine clearance below 30 cc per minute. That's a marker how we measure kidney function and the creatinine clearance more than 60 is usually close to normal. As the creatinine clearance drops and goes below 30, chemotherapy with these platinum agents may become a challenge by itself or if it's combined with the ECOG performance status of 2, which means more patients are not moving most of the day. So those features again have to do with the functionality of the day-to-day life. The presence of significant neuropathy, heart failure, and poor kidney function may potentially make the oncologist recommend immunotherapy versus the standard of care, which is chemotherapy, in those patients. And I would say if someone gets chemotherapy, which is the majority of patients, usually they may get immunotherapy later. So pretty much I would say discuss with the medical oncologist what is the right treatment for you. Most patients get chemotherapy up front, followed by immunotherapy. Some others may need to get immunotherapy, and those criteria help us make that patient selection for the right treatment at the right time. So I just alluded to you that most patients with spread or metastatic urothelial cancer, most of them receive chemotherapy. We discussed some criteria in the previous studies that we may use immunotherapy upfront instead of chemo, but for the vast majority of patients, chemotherapy is used upfront and that was based on the results of phase 3 clinical trial called JAVELIN Bladder 100. This was presented at the ASCO Annual Meeting in 2020 about 2 years ago, and it was published in a big journal. And that study showed that if you give chemotherapy upfront, those patients who can tolerate the chemotherapy, of course, who do not have the previously listed criteria, those patients benefit and live longer, so longer overall survival, meaning they live longer, and they have longer progression-free survival, meaning they live longer without worsening of the cancer if they get immunotherapy with, immunotherapy drug is given through the vein, called avelumab. If that is given after the end of chemotherapy for patients who have a response or stable disease, meaning no progression on chemotherapy. So if you get a complete response, meaning that the CAT scans look normal after chemotherapy as at least we can tell visually. Partial response, meaning that the CAT scans look better, but still we can see some cancer spots. Stable disease, meaning that the scans look stable compared to the beginning before we start chemotherapy. If someone has worsening of the cancer in chemotherapy, then the concept of maintenance therapy doesn't apply. So it's only for patients with complete response, partial response, or stable disease, SD. And the poster we had, and I can tell you - I was a co-author in the abstract and co-investigator in the trial, as a disclosure - was sort of the benefit of the patient with avelumab as maintenance therapy after chemotherapy was notable in patients with complete response, partial response, and stable disease. So in any of these 3 categories, avelumab immunotherapy should be offered as level 1 evidence and benefit patients in terms of overall survival and progression-free survival as long as there's no progression to the upfront initial chemotherapy of the patient with metastatic urothelial cancer received. Many other abstracts on these cancers were presented, and I would encourage you to look at them. Thank you so much for the opportunity today. Greg Guthrie: And thank you, Dr. Grivas. Next, we have Dr. Zhang who will discuss some research in kidney cancer. Dr. Zhang: Hi everyone, glad to be here today. I'll be discussing 2 highlights from ASCO 2022 in kidney cancer. The first one we wanted to highlight was a trial called EVEREST: everolimus for renal cancer ensuing surgical therapy, a phase 3 study. And in context, this study is a trial of evaluating everolimus, an mTOR inhibitor, in the post-surgical context. And we do have in the landscape 2 approved therapies, sunitinib and pembrolizumab. And as we have seen, some effective therapies in the refractory setting, many of these therapies are being tested in this postoperative space. So this particular study of EVEREST looked at patients with renal cell carcinoma who underwent resection for their primary nephrectomy and looking to evaluate postsurgical treatment. So everolimus has been approved as a treatment on its own in the refractory setting as well as in combination with lenvatinib. And so this question of whether everolimus alone could delay or prevent disease recurrence in the postoperative setting was tested in this EVEREST trial. The study ultimately enrolled more than 1,500 patients and assigned them to receiving either everolimus or placebo in the postoperative setting. Of these patients, 83% had clear cell kidney cancer and the remaining had non-clear cell kidney cancer. And the follow-up was quite long, over 5 years, and actually over 6 years, and the researchers looked at time until disease recurrence. And risk of recurrence was actually decreased by 15% in patients who were treated with everolimus compared to placebo. But the prespecified cut-off for a statistical significance was not quite reached, and the researchers took a specific look at a group of very high-risk patients defined by larger tumors, invasion of the perinephric fat in renal veins or invasion of nearby organs or known positive disease. And those patients with very high-risk disease had more benefit from everolimus compared to placebo. Of note, 37% of patients who were treated with everolimus had to stop treatment due to their side effects, and the most common severe side effects included mouth ulcers, high triglyceride levels, and high blood sugars. So ultimately this particular study did not show sufficient benefit of everolimus given the toxicity and lack of statistical significance. And so this is a balance between potential benefit in delaying recurrence versus treatment toxicities that we must have in this adjuvant setting. So what does this particular study mean for patients? Well, it was certainly a large phase 3 trial performed in the cooperative group setting and through the generosity of 1,500 patients and the principal investigators on the study, we learned this answer for a very important question of whether everolimus makes a difference in this postoperative setting. I think we're not using this in clinical context currently, but in this postoperative setting, we are always balancing this risk of toxicity with the potential for benefit and discussing the potential treatment options. I do not think this particular trial changes the standard of care in this adjuvant setting. And then I think finally for today's prepared talks, this abstract on depth of response and association with clinical outcomes with CheckMate 9ER patients treated with cabozantinib and nivolumab. So this was a post-trial analysis of patients who had kidney cancer with disease spread and treated with cabozantinib and nivolumab compared with sunitinib in the CheckMate 9ER study. And the context, this was the phase 3 trial in which the benefit of cabozantinib and nivolumab was established in the first-line setting and gained the registration and approval of this combination in the first-line treatment of metastatic kidney cancer. This particular analysis, presented at ASCO this year, was a post-trial prespecified analysis evaluating this depth of partial responses and associating those with clinical outcomes of time until disease progression as well as time until death. These depth of responses were defined as 80 to 100% for PR-1, 60 to 80% for PR-2, and then 30 to 60% as PR-3. And as we saw in this analysis, the deeper the responses on cabozantinib and nivolumab, the more correspondence with higher 12-month rates of disease-free progression compared with those same depths of responses from sunitinib. And there were similar 12-month overall survival rates for patients with similar depth of responses for either the cabozantinib and nivolumab combination compared with sunitinib. So I do think the degree of partial response in these settings is productive of time until progression and establishes further the efficacy and benefit of cabozantinib and nivolumab compared with sunitinib. And what does this trial mean for our patients? I think that early on, as we're looking for responses and radiographic changes for our patients on cabozantinib, nivolumab in the first-line setting, these deeper responses are associated with longer time until disease progression, and we can counsel patients, to discuss whether cabozantinib and nivolumab is working for them. This could be an early indicator for how patients will do overall on this combination. So with that I'd love to wrap up and turn it back over to you, Greg. Greg Guthrie: Thanks so much Dr. Zhang. And now it's time to move on into our Q&A session. This is for you, Dr. Agarwal. So the question is utility of triple therapy, ADT plus docetaxel plus ASI and metastatic hormone-sensitive prostate cancer given ENZAMET was inconsistent with PEACE-1 and ARASENS. Would you give ASI concurrent or sequential after chemotherapy for tolerability? I'm assuming ASI here is androgen suppression, correct? Dr. Agarwal: Yes. Great question. There are 2 questions here. Number 1, if I would use triplet therapy given the negative subgroup analysis of the ENZAMET trial, and number 2, what is the role of triplet therapy in general? The answer to the first question is ENZAMET trial, subgroup analysis is very different from preplanned, prespecified, well-powered analysis from PEACE-1 and the ARASENS trial. So yes, we saw discrepant results, but my impression from ENZAMET trial is enzalutamide is an effective option for all patients regardless of the receipt of docetaxel chemotherapy because that was a subgroup analysis. So I don't think it really affects negatively the results of the ARASENS and the PEACE-1 trial. But a bigger question here is triplet therapy versus doublet therapy? Is triplet therapy for all or doublet therapy for all? Answer is no. Triplet therapy trials only showed that adding a novel hormonal therapy or deeper androgen blockade to the backbone of ADT plus docetaxel improves survival. These trials did not answer the question, if adding docetaxel chemotherapy to ADT plus, for example, enzalutamide or darolutamide or apalutamide, will improve survival. We do not have that question answered by any of the trials and unlikely any other trial will answer that question. So my take ADT plus docetaxel is replaced by ADT plus docetaxel plus these deeper androgen blocker therapy. So wherever I was going to use docetaxel chemotherapy, so those are the patients with visceral metastases or in my practice, when I do comprehensive genomic profiling, I see those molecular aberrations which predict lack of response to deeper androgen blockade such as baseline AR variants. Or if I see 2 out of 3 mutations of p53, RB loss, p10 loss, if I see 2 out of these 3, I tend to think about docetaxel chemotherapy. So in those patients where I'm using ADT plus docetaxel, I would add another androgen receptor blocker such as abiraterone and darolutamide. But when I'm using enzalutamide or apalutamide which I use for majority of those patients, my patients with metastatic hormone-sensitive prostate cancer, I do not think about triplet therapy. Greg Guthrie: Thanks, Dr. Agarwal. We actually have a follow-up question, and this is, what is the role of oncology in low-stage early prostate cancer? Can neoadjuvant chemotherapy reduce the number of people who end up with metastatic prostate cancer? Dr. Agarwal: This answer is very simple. There is no role of neoadjuvant chemotherapy in high-risk localized prostate cancer or any localized prostate cancer setting. Greg Guthrie: Great. Thank you. Next question. I believe that this is for everybody. How long will it be until the information from the trials discussed will be used in the community clinics? What can patients do to bring this information to their less experienced doctors? Dr. Grivas: So, Greg, just to clarify the question, is it about the translation of the results of the clinic from ASCO to clinical practice, generically speaking, or any particular tumor type or any particular data results? Greg Guthrie: The way I read this question, it's more just kind of a broader scope question about just like, how long does the results of clinical trials make it to community practice, and what role can patients have in perhaps fostering this transmission of information? Dr. Grivas: Of course, I can start briefly, and then my colleagues can add. I would say the world we live in right now, the information travels very quickly. It's much faster compared to the past. And I think there is much more alignment, in my opinion, in terms of information access between academic oncologists and community oncologists. If, for example, a trial result comes at ASCO being presented, and then there's a follow-up approval authority from a regulatory agency, this agent may be accessible to both community and academic practices. Of course, there are always opportunities for education, and Dr. Agarwal is the director of the ASCO Daily News, and he knows that well to disseminate the information well, broadly, in an equitable manner across academic oncologist providers and community providers. And I think CME, continued medical education practices, can help in that regard. And obviously, the other aspect of that is the ongoing clinical trials and how we can do a better job disseminating the opportunity for equitable participation in clinical trials across racial groups, ethnicity groups, minority groups, to give them the chance to participate in ongoing clinical trials that may change the practice down the road, which are just early thoughts. But other colleagues can comment. Dr. Zhang: Yeah, if I could chime in. I think these continuing medical education programs, particularly in the context after large symposia like the ASCO Annual Meeting we just had, are particularly important. And the Best of ASCO series, as well as ASCO Direct Highlight series - I believe Dr. Grivas and I are hosting 2 of these - are very helpful, I think, to bring the latest findings from the ASCO Annual Meeting to our community colleagues. And they really are our colleagues. We work together with our oncologists within the community to take care of our patients, oftentimes for standard of care treatments. Patients can access them more in their backyards. And I think from a patient standpoint on the second part of the question, they're able to hear these from patient-friendly platforms and to bring that to the attention of their oncologist, wherever that may be. It all helps in the grand context of clinical care. So I hope that these trial results and the latest findings from ASCO can get inseminated very quickly.   Dr. Grivas: And to also add very briefly, the role of patient advocacy groups, and in the bladder cancer work, there are many, for example, the Bladder Cancer Advocacy Network, World Bladder Cancer Coalition, and many others can help also in that regard and teaming up with all of us to disseminate information and also clinical trial access. Greg Guthrie: Great. Thank you, everyone. We have a question for Dr. Grivas. After the survey results in the study you described, is there any plan to make a guideline or tool to make sure we standardize the definition of cisplatin/platinum ineligibility? Dr. Grivas: Great question. Just 1 more thing on my prior answer, kudos to Cancer.Net for serving that mission, Greg and Claire in that-- or the previous question to have a complete answer. Answering this new question here, which is very important. I think the next step is to try to publish the results of the survey. The survey like the previous one done by Dr. Galski about 10 years ago-- it's a survey on expert oncologists, and it's a consensus-based definition. It's criteria that we came up with together. And I think the next step here is to publish this in a peer-review process. And our hope is by publishing these results, we can have a more formal definition to help guide our practices in academia, but also in the community oncology practices and make sure that we have a standardized way that we approach this therapy selection and of course, to help design clinical trials that for this particular patient population in order to improve outcomes in this setting. So hopefully publication will come soon. Greg Guthrie: Thanks, Dr. Grivas. I'll just drop a really quick pitch there. Here at Cancer.Net, we do have a very broad array of information on clinical trials. And patients can come visit us at Cancer.Net and learn about clinical trials, what they mean, and how they help advance cancer research. We now have a question for Dr. Zhang. Based on the results of EVEREST and other trials approved systemic therapies in the adjuvant setting like sunitinib and pembrolizumab, are there ongoing other trials in this setting and is risk stratification used? Dr. Zhang: The short answer is yes. There are ongoing adjuvant trials that build on pembrolizumab in the adjuvant setting. There's one that is looking at the addition of belzutifan with pembrolizumab in the adjuvant setting. So that trial is a global trial which is about to get started, if not enrolling already. And in the context of adding on in the adjuvant setting, I do think we really need to discuss with our patients how much of a benefit the treatment will have versus the real toxicity in the postoperative setting, many patients will not have symptoms from their cancer, so they may have some pain or healing side effects from surgery, but they won't have symptoms from cancer. So any toxicities from medications can be further amplified, so are we truly giving a lot of benefit in that context or not. So that's an individualized decision, and I do think conversations must be had to make that decision together. Greg Guthrie: Thanks, Dr. Zhang. I want to ask a question myself of Dr. Gilligan. You had mentioned that microRNA is an emerging field of study, and I've heard about this in other types of cancer as well. I wonder if you could discuss that a little bit more. Dr. Gilligan: Yeah, microRNA, the promise that holds is being a more accurate detector, specifically of testicular cancer. So the problem we have with alpha fetoprotein and beta HCG is half of the testicular cancers may not make 1 or both of those markers. So people can relapse without the markers going up, even though markers are most commonly what we see, there are a couple of different scenarios. Someone has stage I testicular cancer, which means their testicles removed and all their scans show no evidence of cancer. We know that 25% or so of non-seminomas and 20% or so of seminomas will relapse, even though we can't see what the cancer is, and the markers are negative in that situation. MicroRNA may be able to detect those people who still have cancer much, much earlier. So we know that they're, in fact, not stage I and that they need active treatment right away. So that's one place. Another place that we're seeing evidence is that men who've had metastatic testicular cancer. They go through chemotherapy, and they have residual masses. And we're wondering if there's cancer in those masses or is it all dead scar tissue or is it teratoma? MicroRNAs may be able to allow us to determine who needs additional treatment, who needs surgery without having it. Right now, we typically go in and operate just to figure that out. So there are a number of situations in which we could more accurately stage patients and figure out who's cured and who's not cured much earlier in the course of disease. And for a patient, this would be fantastic, because right now, if you've got stage I disease with non-seminomas and you go on surveillance and somebody says you have a 25% risk the cancer is going to come back, that's a 1 in 4 chance that at some point in the next 2 years, most likely, or longer, you're going to have to suddenly drop everything and go through months of chemotherapy. If we knew on day 1, it looks like you're cured, but in fact, there's cancer hiding there somewhere, and we need to treat you now, that would be helpful to know so they can get it over with. And the other men, we could say we're really extremely confident that there's not a 25% risk, it's a 5% risk or something much lower. So there are a number of ways, if this really gets proven and there's emerging data that's promising, I think we could reassure men, treat them more appropriately, spare them unnecessary treatment, and give them more peace of mind. Greg Guthrie: Great. Thanks, Dr. Gilligan. I think we have a question from Dr. Grivas now. Dr. Grivas: Thank you, Greg. This is a great panel. I like to learn from my colleagues here. One question for Dr. Zhang, you have done so much work in the field, leading the field there, Dr. Zhang. Any comments about the ideal end points in the adjuvant setting in kidney cancer, urothelial cancer, disease-free survival or overall survival? Would you comment about how we design trials, and what will be an acceptable benchmark? And what is meaningful for patients, too, in the adjuvant treatment after radical surgery for kidney cancer and urothelial cancer? Dr. Zhang: Oh, that's a great question, Petros. Thank you so much for asking. We have discussed this many times together because you and bladder cancer and myself and kidney cancer, we're thinking a lot along the same lines right as new immunotherapies get approved in the postoperative setting, so disease-free survival as an endpoint and recurrence-free survival as an endpoint is a valid endpoint. It's a direct result of the randomized treatment on the trial, so I do think that is the valid endpoint, and it's an endpoint that the FDA has approved the sunitinib and pembrolizumab indications in kidney cancer, nivolumab and bladder cancer. So I think it's certainly a valid endpoint to delay disease recurrence. How much of that is meaningful degree of improvement for an individual patient? Their own measure of recurrence is either yes or no. It's much more binary than population effects. So how much does that translate into benefits for the patient? I think that warrants deeper individualized discussion. But these disease-free survival endpoints in all of these studies is a valid endpoint to see whether the treatment is worthy in delaying disease recurrence in each of these disease types. Greg Guthrie: Thanks, Dr. Zhang. We have one last question here, and I believe this is a follow-up for Dr. Gilligan. And what is the time frame for the rollout of microRNA 371 to the community? Dr. Gilligan: I don't know the answer to that. I'm not sure that we have enough data right now that it's going to get approved. I think we're headed in the right direction, but it's very hard to know what the timing of that is. There are trials going on, so I don't know at the moment of exactly what the scenarios are in which people are going to be, which patient populations are going to be eligible, but there are trials going on. I think I'm hoping within the next 2 years or so, but I really don't know what the time frame is, unfortunately. Dr. Grivas: And if I may add a more generic comment to Dr. Gilligan's wonderful answer is that when we have what we call biomarkers that are like metrics that can give us information about how the patient does over time, it's important to tease out what we call prognostic, meaning how can this biomarker give us a sense of the chance of recurrence, as Dr. Gilligan said, or death from the cancer. But also, the bigger question is, is it going to give us information to predict benefit from an individual therapy? And that's a bigger question in oncology that is a harder one. This predictive question and try to identify biomarkers and validate them to make sure they have, they're clinically useful. They can help us make treatment decisions in the clinic. And I'm very excited about what Dr. Gilligan discussed about the promise in the future. But more trials are needed for many biomarkers. Dr. Gilligan: I think when we do this update next year, we'll have significantly more data then, I'm hopeful. Greg Guthrie: Thank you to you all. Thank you, Dr. Agarwal. Thank you, Dr. Grivas. Thank you, Dr. Gilligan. Thank you, Dr. Zhang, for sharing this great research with us, as well as your expertise. It's been a real pleasure this afternoon. And to all of our viewers, thank you for joining us. You can find more coverage of the research from ASCO Annual Meeting and other scientific meetings at the Cancer.Net blog, which is at www.cancer.net/blog. And if you're interested in more Cancer.Net content, please sign up for a monthly Inside Cancer.Net newsletter or follow us on social media. We're on Facebook, Twitter, and YouTube where our handle is always @CancerDotNet, with dot spelled out. Thank you all, and be well. Thanks. ASCO: Thank you, Dr. Agarwal, Dr. Gilligan, Dr. Grivas, and Dr. Zhang. You can find more research from recent scientific meetings 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.

Dr Pal walks us through research presented at the 2022 Genitourinary Cancers Symposium, including data from the TIVO-3 trial (NCT02627963) and findings from the NeoAvAx trial (NCT03341845) exploring avelumab (Bavencio) plus axitinib (Inlyta) for patients with high-risk, nonmetastatic clear-cell renal cell carcinoma.

In this podcast, Dr. Alicia Morgans discusses recent data presented at the 2022 ASCO GU Cancers Symposium, including trials evaluating the use of first-line PARP inhibitors in combination with abiraterone for mCRPC, continuation of enzalutamide after progression, and imaging modalities as predictive and prognostic biomarkers. This activity is available for CE/CME credit. Claim your credit at pce.is/ascogu.Contributors: Dr Morgans has disclosed that she has received funds for research support from Atellas, AstraZeneca, Bayer, Myovant, and Pfizer, and consulting fees from AAA, Astellas, AstraZeneca, Bayer, Blue Earth, Clovis, Dendreon, Janssen, Lantheus, Merck, Myovant, Novartis, Pfizer, Sanofi, and Telix.Ms Martone has no relevant conflicts of interest to report. 

Featuring perspectives from Drs Shilpa Gupta, Daniel Petrylak and Guru Sonpavde, moderated by Dr Sumanta Pal, including the following topics: Introduction (0:00) Integrating Novel Agents into the Treatment Paradigm for Nonmetastatic Urothelial Bladder Cancer (UBC) — Sumanta Kumar Pal, MD (1:46) Current and Future Front-Line Management of Metastatic UBC (mUBC) — Shilpa Gupta, MD (23:48) Selection and Sequencing of Therapy for Relapsed/Refractory mUBC — Daniel P Petrylak, MD (47:01) Tolerability/Toxicity of Novel Treatment Strategies and Practical Considerations in the Management of UBC — Guru Sonpavde, MD (1:08:27) CME information and select publications

Featuring perspectives from Drs Neeraj Agarwal, Himisha Beltran, Fred Saad and A Oliver Sartor, moderated by Dr Alan Bryce, including the following topics: Introduction (0:00) Optimal Use of Hormonal Therapy in Nonmetastatic Prostate Cancer (PC) and Metastatic Hormone-Sensitive Disease — Fred Saad, MD (4:18) Selection and Sequencing of Therapy for Patients with Metastatic CRPC (mCRPC) — A Oliver Sartor, MD (29:57) Integration of PARP Inhibitors into the Current Management of mCRPC — Himisha Beltran, MD (53:42) Available Data with, Ongoing Investigation of and Potential Future Role of PARP Inhibitor-Based Combinations — Alan H Bryce, MD (1:18:49) Novel Investigational Strategies for Patients with PC — Neeraj Agarwal, MD (1:44:48) CME information and select publications

In this episode, we're highlighting three presentations from the ASCO Genitourinary Cancers Symposium, held recently in San Francisco.To listen to more podcasts from ASCO, visit asco.org/podcasts.

The 2022 ASCO Genitourinary Cancers Symposium kicked off this week. On this episode, we'll hear about two studies presented at the meeting: one, focused on a genetic risk score that may aid in identifying men with high vs low lifetime risks of developing metastatic prostate cancer or dying from prostate cancer; and the second, about a trial that tested the efficacy of combination immunotherapy and tyrosine kinase inhibitor therapy for renal cell carcinoma.Coverage of stories discussed this week on ascopost.com:Comprehensive Genetic Risk Score May Predict Risk of Developing Metastatic Prostate Cancer or Death From Prostate Cancer Across Diverse PopulationsTo listen to more podcasts from ASCO, visit asco.org/podcasts.

ASCO: 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 world's leading professional organization for doctors who care for people with cancer. The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Cancer research discussed in this podcast is ongoing, so the data described here may change as research progresses. In the Research Round Up series, members of the Cancer.Net Editorial Board discuss the most exciting and practice-changing research in their field and explain what it means for people with cancer. In today's podcast, 4 Cancer.Net Specialty Editors discuss new research in prostate, bladder, kidney, and testicular cancers presented at the 2021 Genitourinary Cancers Symposium, and 2021 ASCO Annual Meeting. This episode has been adapted from the recording of a live Cancer.Net webinar, held June 16th, 2021, and led by Dr. Neeraj Agarwal, Dr. Tian Zhang, Dr. Petros Grivas, and Dr. Timothy Gilligan. Dr. Agarwal directs the Genitourinary Oncology Program at the Huntsman Cancer Institute at the University of Utah. Dr. Grivas is the clinical director of the Genitourinary Cancers Program at University of Washington Medicine. He is also an associate member of the clinical research division at the Fred Hutchinson Cancer Research Center. Dr. Zhang is an associate professor of medicine at Duke University School of Medicine and is a medical oncologist at Duke Cancer Institute. Dr. Gilligan is an Associate Professor and Medical Oncologist at the Cleveland Clinic Taussig Cancer Institute. Full disclosures for Dr. Agarwal, Dr. Grivas, Dr. Zhang, and Dr. Gilligan are available at Cancer.Net. Greg Guthrie: So today, let's introduce our participants. First we have Dr. Neeraj Agarwal of Huntsman Cancer Institute and University of Utah and the Cancer.Net Specialty Editor for Prostate Cancer. Next we have Dr. Petros Grivas from Fred Hutchinson Cancer Research Center and University of Washington. He is the Specialty Editor for Cancer.Net for Bladder Cancer. Next we have Dr. Tian Zhang of Duke Cancer Institute. And she's our Cancer.Net Specialty Editor for Kidney Cancer. And last, we have Dr. Timothy Gilligan. He is with the Cleveland Clinical Taussig Cancer Institute and the Specialty Editor for Testicular Cancer. So to start off, we'll have Dr. Agarwal talking about prostate cancer. Dr. Agarwal: Thank you, Greg. It's such a privilege and honor to be here discussing these studies. So I would like to start with the first study, which was led by Dr. Stephen Freedland, a urologist at the Cedars-Sinai Medical Center in Los Angeles and was co-authored by me, Dr. Dan George, and many others. And here in this study, we present the utilization of therapies, which are associated and known to be associated with very significant, in fact, I would say dramatic improvement in overall survival, as shown by multiple randomized control trials over the period of the last 5 to 6 years. Just to take a step back for the audience, until 2014, standard treatment for metastatic castration-sensitive prostate cancer or newly diagnosed metastatic castration-sensitive prostate cancer used to be androgen deprivation therapy. And combining androgen deprivation therapy with those medications which were approved in the castration-resistant metastatic prostate cancer setting. So basically, using those drugs upfront led to dramatic improvement in overall survival with 33% to 35% reduction in risk of death across those clinical trials. So we actually wanted to look at the real-world utilization, so look at the real-world users of these medications in these patients who are being diagnosed with -- newly diagnosed metastatic prostate cancer in the United States. We also wanted to see how patients who belong to minority populations or racial minority populations, how they are being treated with these medications, which are backed by level 1 evidence. So this was a retrospective analysis of a Medicare database, more than 35,000 patients were included from 2009 to 2018. And we can see here a very representative patient population, predominantly white patients, 11.8% were African American, and 5% were Hispanic. And here are the results. From 2010 to 2014, the use of standard androgen deprivation therapy with bicalutamide, was used in 97% of patients. We did not have trials reporting by that. Let's go to 2015 to 2016. Docetaxel was already approved in this setting now, and we can see some patients received docetaxel, but a small minority of patients received docetaxel. And then let's move to 2018, which is 4 or 5 years after docetaxel data had been presented by Dr. Sweeney in the ASCO plenary session. And abirateron was approved in 2017, and we are still seeing even like almost 2 years after -- we are still seeing the vast majority of patients being treated with standard androgen deprivation therapy or standard deprivation therapy with bicalutamide. So 62% plus 19%, we are talking about almost 80% of patients still not being treated with standard of care treatment, which is androgen deprivation therapy plus docetaxel, or androgen deprivation therapy plus abiraterone at this point of time, and now we have 2 more drugs available, which include enzalutamide and apalutamide in this study. Another interesting thing was if you look at the patients who belong to minority populations, so let's look at African American patients compared to Caucasian patients. The use of intensified therapy was numerically lower. So in Caucasian patients, we are seeing higher use of intensified, as we call them, intensified therapy, or therapies which are considered standard of care, compared to African American men. So overall, the use was lower across the board, but if you look at African American men, the usage was even lower. So this is definitely concerning. I call it alarming, underutilization of life-prolonging therapy in patients who are being diagnosed with newly -- or new diagnosis of metastatic prostate cancer, and we definitely can improve this. We can definitely offer better care to our patients. It is not acceptable in my view to have 30% or less patients receiving standard of care therapies. So with that, I'll go to the next study.  Greg Guthrie: Great, thanks. And this study is, “Health-related quality of life and patient-reported outcomes at final analysis of the TITAN study of apalutamide versus placebo in patients with metastatic castration-sensitive prostate cancer receiving androgen-deprivation therapy.” And you were the presenting author of this, Dr. Agarwal? Dr. Agarwal: Yes, Greg, thank you for giving the opportunity to present this study. And this is basically the continuation of the previous trial. I will not delve into in-depth analysis of these data. I just wanted to show that quality of life is not being impacted adversely by using intensified androgen deprivation therapy, so if you are using these drugs, which improves survival in a very significant fashion, and they are not being used in our patients, as we just saw in the previous study, what could be the reason? Is it the concerns about quality of life or adverse impact on quality of life? If that is the concern, this study, I think, helps refute those concerns. And in this study, which was a large study known as the TITAN trial, which led to approval of apalutamide for patients with hormone-sensitive or castration-sensitive metastatic prostate cancer and showed improved survival and radiographic progression-free and overall survival. We looked at quality of life data as reported by these patients, and these quality-of-life data were assessed by very standardized, validated scales known as FACT-P, or Functional Assessment of Cancer Therapy Prostate scale, or Brief Pain Inventory tool. And there are many other tools. So I will show you the results. And we can see here consistently there was no difference in quality of life as reported by the patients, or I would say any adverse impact on quality of life for these patients in any of these questions. As they were taking these questionnaires. So whether it was physical wellness, emotional wellness, functional well-being, social, or family, we go in and look at fatigue and there was no adverse impact on quality of life. At least from this perspective, we should not be concerned about using these drugs up front in our patients who have newly diagnosed metastatic prostate cancer.  Greg Guthrie: Great. And so what does this mean for patients?  Dr. Agarwal: From patient perspective, we can see here very clearly that using standardized tools, very validated tools, which have been used in multiple trials in the past, patients are not reporting any adverse impact on their quality of life when being treated with intensified androgen deprivation therapy. In this context, apalutamide. Greg Guthrie: Great. Alright. So let's move on to our next study, which is, “Phase 3 study of lutetium-177-PSMA-617 in patients with metastatic castration-resistant prostate cancer.” The VISION trial. Dr. Agarwal: Thank you. In my view, this is 1 of the most important studies presented in the 2021 ASCO Annual Meeting. This study was a phase 3 study where 7,000 patients were recruited, and they had metastatic castration-resistant prostate cancer and had disease progression on a prior novel hormonal therapy such as enzalutamide or abiraterone and the patients had received a taxane chemotherapy. So at least 1 taxane chemotherapy was required before the trial, and the patient had to have disease progression on a novel hormone therapy. These patients were randomized in 2 to 1 fashion to a novel drug, which is a type of radiation, intravenous radiation, as I would explain to my patients, and this is known as beta radiation. And this is a novel radiotherapy where radiation particle, which is delivering beta radiation particle to the cancer cells, is tagged to a molecule, which binds with the prostate cancer cells. So I'm simplifying it for the sake of our patients. And this particle or this compound was added to standard of care therapy and patients were randomized to standard of care therapy versus standard of care therapy plus this new compound. And standard of care therapy was a novel hormonal therapy or anything which did not include chemotherapy or radium 223, which is another type of radiation particle, but a different kind of particle known as alpha particle. So in this study, radiographic progression-free survival and overall survival were primary endpoints. We can see here that the study met both primary endpoints. There was a significant improvement in radiographic progression-free survival with an almost 5 month, 5.4 months, to be precise, improvement in radiographic progression-free survival, with a 60% reduction in risk of disease progression or death. If you look at overall survival, it was also improved in a significant fashion in patients who received the new compound known as lutetium-PSMA-617, and the median survival was improved by 4 months with an approximately 40% reduction in risk of death.  This was a well-tolerated drug overall, and if you look at hybrid side effects, treatment, and emergent side effects, there were 52.7% of patients in the experimental arm, and 38% in the control arm had those treatment-related side effects. So overall, Wwell-tolerated regimen with improved overall survival and radiographic progression. Thank you very much. Greg Guthrie: Thank you, Dr. Agarwal. This is really interesting, and it will be interesting to see if this treatment does change standard of care based on this research. Let's move on to Dr. Grivas and bladder cancer research. Let's see, so Dr. Grivas, your first study is, “Avelumab first-line maintenance for advanced urothelial carcinoma: analysis of clinical and genomic subgroups from the JAVELIN Bladder 100 trial.” And Dr. Grivas was a co-principal investigator in this trial and is senior author of the New England Journal of Medicine publication and co-author of this abstract. Go ahead, Dr. Grivas.  Dr. Grivas: Thank you so much, Greg, and thank you to Cancer.Net for the opportunity, and thanks to the audience. We welcome questions. I would like to update the audience today about the data we saw at the ASCO meeting, and I would like to place this data in context, and I would remind the audience the JAVELIN Bladder 100 trial that changed clinical practice was initially presented last year at the ASCO Virtual Meeting 2020 by Professor Powles. And this particular trial tried to answer the following question: does the immunotherapy, especially the PD-L1 inhibitor avelumab, add value in patients who completed chemotherapy in the first-line setting of metastatic urothelial cancer compared to just best supportive care in terms of longer life, in terms of overall survival, and time until the cancer grows or death, progression-free survival? This is important because until this study came about last year, the practice was, in the setting of spread metastatic urothelial cancer, when the chemotherapy stops, was we cannot give it for a long time because of potential side effects. Usually you used to wait until the cancer grows back, it progresses, or grows. So this trial compared this approach, the best supportive care, versus the immunotherapy with avelumab and the best supportive care. This particular trial, so the significant improvement of life expectancy and overall survival as well as progression-free survival, time until progression of the cancer or death, in the patients that received this immunotherapy drug avelumab as a way to maintain or sustain the benefit that is seen with chemotherapy. So we call this a maintenance therapy approach because we tried to maintain or sustain the benefit with chemotherapy. I want to highlight that this was published in the New England Journal of Medicine and the audience can retrieve that from PubMed if one wants to read the manuscript. The bottom line is this trial changed practice, and we can go now to updates. We saw this in this particular meeting, ASCO 2021, and I think the main question was, are there any particular subsets of patients, different categories of patients, who benefit more from the avelumab maintenance approach, or does this benefit all the patients? And we saw at the ASCO meeting, we saw that the benefit with this immunotherapy appears consistent across the board, across different subcategories of groups of patients. And I think that it's important to point out that we looked at patients who had what we call local disease around the bladder, that was invading this area, and the pelvic side wall that was not amenable to surgical rejection and also patients with spread of the cancer in distant sites, what we call metastasis. And we look at patients who had a primary origin in the bladder or higher up in the urinary tract, what we call kidney pelvis, or ureter, and we call this upper urinary tract, versus the lower tract, which is the bladder, and we also look at patients who had metastatic spread in the lymph nodes only or other parts of the body. And with the bottom line, we saw that the benefit with the immunotherapy was consistent across the different groups of patients. So many patients benefit from this treatment, again, with variable degrees, variable magnitude of benefit, but overall, the bottom line is, take home message is if you have clinical factors or other molecular factors, we do not have a reliable, accurate tool to select which patients should go with avelumab, so we offer it nowadays in every patient who has no contraindication to get immunotherapy and has received some disease control. Meaning a response of the cancer or stabilization of the cancer with the chemotherapy phase. So that has real clinical implications, and I encourage the audience to discuss with their oncologist about the optimal roles of immunotherapy with this maintenance setting after chemotherapy when this is controlled with chemotherapy. Just for context here, I want to highlight the options the patients have in clinical practice. And when someone is diagnosed with spread urothelial cancer, they can be offered nowadays avelumab as a maintenance strategy to maintain the benefit of chemotherapy, and the other options include immunotherapy up front, like drugs like pembrolizumab or atezolizumab, and I will come back to that question how to select your treatment in my last slide. And I want to point out these are the options, and obviously clinical trials are always a great option for patients, and they should ask their oncologist about those options. So since I talked about immunotherapy, I want to point out that the ideal chemotherapy is cisplatin-based chemotherapy. Not everybody has enough fitness of the body to tolerate cisplatin. For those patients, we think cisplatin may be too much, we use carboplatin/gemcitabine, and we use avelumab maintenance in that scenario. What about immunotherapy after that? Is there data supporting that use? And the answer is yes. There is some data suggesting that immunotherapy can be an option for some of the patients, and in this particular slide, we update the data from another clinical trial. And I will let Greg, you can read the title of that. Greg Guthrie: Sure, so this study is, “First-line pembrolizumab in cisplatin-ineligible patients with advanced urothelial cancers response and survival results up to 5 years from the KEYNOTE-052 phase 2 study.” Dr. Grivas, you're a co-author on this study. Dr. Grivas: That's right, thank you, Greg. This trial presented longer follow up to see what happened in patients who received the immune checkpoint inhibitor anti-PD called pembrolizumab because they were not fit enough to get cisplatin chemotherapy. Keep in mind this was designed before the previous study I showed you presented the results and included patients who were not fit for cisplatin, but some of them could have been fit for carboplatin. There was no comparison here, everybody received pembrolizumab as a single agent, alone, and in this particular study, we would try to see the degree of shrinkage of the cancer and the overall response rate as well as how long people lived over time. So with longer follow-up, by the way, we published this study in the Lancet Oncology years ago, and we have longer follow-up, and what you see here is a degree of shrinkage of the cancer, what we call overall response rate, was about 29% in what we call all comers, and it was higher size of tumor shrinkage in patients with high PD-L1 expression. PD-L1 is this brake of the immune system, the checkpoint of the immune system and highly expressive measured by particular assay that pembrolizumab works better in those patients. However, some patients even with low PD-L1 measured by this CPS score I put in the slide still might have benefits, so the take-home message here is there is a particular proportion of patients who can benefit from the checkpoint inhibitor pembrolizumab. PD-L1 can be used in that setting to help decide between chemotherapy and immunotherapy. However, we have not compared directly the chemotherapy followed by the available maintenance with immunotherapy up front, so this question is still lingering. However, if the patient has a response shrinkage to pembrolizumab, many of those patients may have a long-lasting response. We tried to figure out with research how can we predict who is going to benefit more from this treatment as a matter of ongoing research. Greg Guthrie: Dr. Grivas, can you really quickly define CPS for our audience? Dr. Grivas: Absolutely. Great question. CPS is a tool we use in the pathology labs to measure the PD-L1 expression. It can be measured by different assessing antibodies, and the pathologists use a score to define if the PD-L1 is high or low. In this particular study, CPS of 10 or higher defines PD-L1 high expression, CPS below 10 defines PD-L1 low expression, and this appears to have some association with a chance of the tumor shrinking with immunotherapy with pembrolizumab. Greg Guthrie: Great. Thanks, Dr. Grivas. So our last study is, “Pembrolizumab versus investigator's choice of paclitaxel, docetaxel, or vinflunine in recurrent, advanced urothelial cancer: 5-year follow-up from the phase 3 KEYNOTE-045 trial.” Dr. Grivas Very quickly, this study compared immunotherapy, pembrolizumab, the anti-PDL1, compared to chemotherapy with paclitaxel, docetaxel, or vinflunine, the latter one is in Europe, after progression of cancer growth on platinum-based chemotherapy. This was published in the New England Journal of Medicine a few years ago, and pembrolizumab prolonged survival, people lived longer compared to the chemotherapy. And this longer follow-up presented by Dr. Bellmunt and colleagues, showed the sustained results with follow-up, this population of patients had already received cisplatin-based chemotherapy and the cancer progressed, growth, despite that chemo, and in those patients, pembrolizumab appears to produce better results compared to this salvage chemotherapy shown in that slide. And this has implications because immunotherapy can be used in those patients after progression on platinum-based chemotherapy. And just to wrap up here the discussion, I just want to give the options to the patients, see if someone has a new urothelial cancer, options include cisplatin/gemcitabine, or if someone is not fit enough for cisplatin, carboplatin/gemcitabine, and both of those scenarios can be followed by avelumab, and those with shrinking or stable disease, patients who have progression on platinum-based chemotherapy can get pembrolizumab and of course other options available. We can go into another podcast, and I encourage the audience to look and discuss with their oncologist about those options, and the take home message, the clinical trials is what got us here, and I recommend clinical trials to be discussed with your oncologist. Thank you so much, and I'll be happy to take questions.  Greg Guthrie: Thanks, Dr. Grivas. So we're going to move on to Dr. Zhang, who is going to talk about kidney cancer. So our first study today is, “Pembrolizumab versus placebo as post-nephrectomy adjuvant therapy for patients with renal cell carcinoma: a randomized, double-blind, phase III KEYNOTE-564 study.” Dr. Zhang: Thanks, Greg. I'm really excited to be here today and thanks, everyone, for joining. KEYNOTE-564 was presented at the ASCO plenary by our colleague Dr. Toni K. Choueiri, and this is a highly anticipated study in the adjuvant space for kidney cancer and enrolled patients with high-risk clear cell kidney cancer who had undergone either nephrectomy or a metastastectomy, removing their few sites of metastatic disease and treating those patients with either pembrolizumab for up to a year or placebo. And the endpoint was disease-free survival, and enough events had occurred by this ASCO for us to see the primary results. So the overall -- the study was positive. For the primary endpoint, disease-free survival improvement was met with a hazard ratio of 0.68 and the estimated disease-free survival rate at 2 years was 77% for patients treated with pembrolizumab versus 68% for patients treated with placebo. The overall survival favored pembrolizumab, but it was not yet statistically significant, and follow-up will be needed. Overall, we see an improvement in disease-free survival delaying time until recurrence for patients treated with pembrolizumab, and this was the first study in this adjuvant space showing checkpoint inhibition has a role in adjuvant treatment of renal cell carcinoma.  Greg Guthrie: Thanks, Dr. Zhang. Our next study is, “Pembrolizumab plus axitinib versus sunitinib as first-line therapy for advanced clear cell renal cell carcinoma: results from 42-month follow-up of KEYNOTE-426.” Dr. Zhang: This study, KEYNOTE-426, we are all very familiar with. Pembrolizumab and axitinib has been used for the last 2 years in the first-line treatment of clear cell metastatic kidney cell cancer, and it's a longer-term follow-up, more events and more understanding of what happens to these patients once they're treated in a longer term, so primary endpoints of course of this phase 3 study were progression-free survival and overall survival. When we're looking at this medium duration of follow-up at 42 months, so about 3 and a half years, pembrolizumab and axitinib improved both median overall survival as well as median progression-free survival. We'd point out that the -- at the 3 and a half year mark, the overall survival rate for patients treated with the combination was about 57.5%. And the progression-free survival rate was about 25%, so about a third of patients had not had progression of disease at 3 and a half years. Which is quite meaningful if they can stay on their first-line treatment for that long. The objective response was 60%, and of note, the complete response rate had been updated to about 10%. So there are some patients that do have delayed complete responses. And no new safety signals were observed. So overall, certainly still provides a lot of evidence to treat with pembrolizumab and axitinib for patients in the front-line setting. Greg Guthrie: Great. And our last study here is, “Health-related quality of life analysis from the phase 3 CLEAR trial of lenvatinib plus pembrolizumab or everolimus versus sunitinib for patients with advanced renal cell carcinoma.” Dr. Zhang: This was the phase III trial in first-line treatment of metastatic clear cell kidney cancer that was reported at GU ASCO in February of 2020, and it was a 3-arm randomization to lenvatinib with everolimus in the standard study, and lenvatinib with pembrolizumab or sunitinib alone, and we saw the efficacy data in February, and here we're seeing the quality of life outcomes, and looking at how patients are doing, patient-reported outcomes on these treatments. And so with multiple quality of life measures, we're seeing improvements in patients that had better disease-related scores of symptoms when treated with lenvatinib and pembrolizumab versus sunitinib. We're seeing pain scores improve and patients having less diarrhea, appetite loss, when we're comparing against sunitinib. Of note, it's hard to specifically tie a particular symptom, if that's improved, because they've had better disease control or if it's more from the treatment side effect itself. So still hard to tease out a causality in these quality of life measures, but overall, improvement in patients' quality of life when treated with lenvatinib and pembrolizumab. And certainly provides some more data for patients receiving this combination. And so I just wanted to highlight our ongoing phase 3 combination trials and first-line metastatic kidney cancer. PIVOT-09 with bempegaldesleukin has completed accrual in the first triplet of COSMIC-313 with ipilimumab, nivolumab and cabozantinib has completed accrual, so the actively enrolling studies currently are PEDIGREE and PROBE. These are studies that are being carried out in the cancer cooperative groups, as well as a triplet belzutifan lenvatinib with pembrolizumab, a study that Merck is running and all 3 very important studies we will continue to learn from and answer some important, clinically relevant sequencing treatment discontinuation, nephrectomy side effect questions. Thanks to everybody. Greg Guthrie: We have 1 more. So, “Clinical activity of durvalumab and savolitinib in MET-driven, metastatic papillary renal cancer.” Dr. Zhang: Dr. Rodriguez from Spain presented this of papillary renal cell carcinoma treated with savolitinib and durvalumab, and specifically looked at the MET-driven subset of 14 patients out of these 42 patients. The efficacy primary end point was objective response rate. And of note, and median progression-free survival for the 42 patients who were all treated, it was 4.9 months and in MET-driven disease, so savolitinib targets MET, so MET-driven disease was 10.5 months and the median overall survival in everyone was 14 months, versus MET-driven was 27 months, and also higher response rates for patients with MET-driven disease. So I think personally, hypothesis generating, we will likely be seeing more trials with durvalumab and savolitinib in MET-driven papillary renal cell carcinoma. Greg Guthrie: Thank you, again, Dr. Zhang. And Dr. Gilligan, we're going to talk about some testicular cancer research now, and the first study is, “Testicular cancer in the cisplatin era: causes of death and mortality rates in a population-based cohort.” Dr. Gilligan: So this study was looking at what happens with testicular cancer patients who are cured of their cancer, are they at risk of dying of other causes? They looked at over 5,000 men treated between 1980 and 2009, so it's important to recognize that some of the treatments given back then are a little different than the way they're given now. And it looked at the risk of death from causes other than testis cancer compared to men without testicular cancer in the general population, and the concerning finding from this study, and it's not the first study to report this, was that the risk of non-testicular cancer death, that is, death from other causes, was increased by about 28% in men who had been treated with radiation therapy and about 23% in men treated with chemotherapy. There's a risk of non-testicular cancer death, the risk, excuse me, was doubled in those whose treatment included both. So it was higher with either radiation or chemo and it was actually 100% higher or double than both those who had chemotherapy and radiation. As you got more chemotherapy, the risk went up. There was no trend towards the increase with just 1 or 2 cycles. We started to see the increase with 3 cycles, and it became statistically significant with 4 cycles. But there wasn't much difference between 3 and 4 in terms of the absolute number that was seen. In terms of death from other cancers, so why is this happening? Other cancers are a major issue after chemotherapy or radiation. Again, the risk was increased 60% after radiation therapy and 43% after chemotherapy, and those who got both, the risk of cancer was 3 times higher than the general population. So that's in men who had chemotherapy plus radiation therapy. Fortunately, there are not a lot of men who get both of those treatments anymore. Non-cancer deaths increased 17% after chemo and 55% of treatment included both. So the risk for non-cancer deaths was not as high as the risk for death from secondary malignancies. Interestingly, the risk of suicide increased 63% in men treated with chemotherapy. That's not affecting as many men as those other numbers, even though 63% number looks high, but it is a concern. Those treated only with surgery did not have an increased risk of non-testicular cancer death. What does this mean for patients? It really means when we can use surgical treatments instead of chemotherapy or radiation as an additional incentive to try do that, and what that may mean is there should be a larger role for retroperitoneal lymph node dissection as an alternative to chemotherapy or radiation therapy. Secondly, for patients getting chemotherapy, it's important to minimize the number of cycles of chemo as long as we're not sacrificing long-term cure rates, because the biggest risk of death is dying from the cancer, but that means limiting to the 3 cycles instead of 4 cycles is probably a good idea, and I think it's an argument to use 3 cycles of BPE instead of 4 cycles of EP because it's really the etoposide and the cisplatin that is linked to the secondary cancer risk, not the bleomycin, as far as we know. And then lastly, we need to pay attention to the mental health needs of men treated with chemotherapy. That there is more emotional distress and we're seeing here a higher risk of suicide.  Greg Guthrie: So our second trial is the, “SEMS trial: result of a prospective multi-institutional phase 2 clinical trial of surgery in early metastatic seminoma.” Dr. Gilligan: So if we're going to use more retroperitoneal dissection and less chemotherapy or radiation, 1 place to do that is in stage 1 and stage 2 seminoma, and many centers around the country have started doing that, and this was a trial that looked at that approach. So these are men who normally would be treated with chemotherapy, 3 cycles of BEP, or radiation therapy to the back of the abdomen and part of the pelvis potentially. This study looked at the small number of patients, 55 men, low volume, stage 2 seminoma up to 3 centimeters of size and maximum dimension. And what they reported of those men undergoing retroperitoneal lymph node dissection, 10 relapsed, so 18% relapsed after median follow-up of 24 months, they were all alive at the end of the study. No deaths. 8 of 10 relapses were treated with chemotherapy, and 2 were treated with additional [surgery]. Out of the 55 men, 8 ended up getting chemotherapy. Normally, all of them would have gotten either chemo or radiation. Relapse-free survival was 87%, overall survival was 100%. Seven (7) patients developed complications after RPLND and 5 of them were mild. Two (2) were more severe. So it's a well-tolerated treatment, if it's done at a large volume center, it's worth noting that the centers participating in the study were large volume centers. Again, if not treated with RPLND, all of these men would have gotten chemo or radiation. The relapse rate after chemotherapy or radiation is about 5%. So the relapse risk is higher after surgery, but in the sense, if we take 100 men with early stage 2 seminoma and do an RPLND instead of chemo or radiation, we can spare 80% of them the long-term effects of chemotherapy or radiation. Alternatively, if the priority is simply to prevent a relapse, radiation therapy and chemotherapy are more effective at that, the relapse risk being 5% but at the cost of long-term side effects from chemotherapy or radiation. Bottom line there is an additional treatment option for low volume stage 2 seminoma for men who prioritize avoiding the complications of chemotherapy or radiation therapy. Both of which are associated with an increased risk of death from other causes. The price we pay for that is the relapse risk is higher with RPLND compared to the other approaches. Not all centers are going to be offering this, but major centers that do a lot of testicular cancer, this is becoming a new treatment option. With the caveat that we have less experience with this approach. This is a relatively small study. And we have a lot more experience with chemotherapy or radiation. I don't think there's a one size fits all here, but I think patients should talk about it with their doctor. If they have early-stage seminoma, they should talk about surgery as an alternative to radiation or chemo. Greg Guthrie: Here we go. “Surveillance after complete response in patients with metastatic non-seminomatous germ-cell tumor.” Dr. Gilligan: So this study is looking at the question, if you take a man who has retroperitoneal lymph nodes that are enlarged and metastatic non-seminomatous testis cancer with lymphadenopathy in the back of the abdomen and you put them through chemotherapy and at the end, all retroperitoneal nodes are now within normal limits, normal size nodes, and no bigger than 10 millimeters or 1 centimeter, do we need to do a retroperitoneal lymph node dissection on those patients? Some centers recommend it and some don't. This looked at 388 men in that situation. They were put on surveillance. These men did not undergo the post-chemo RPLND. Two years survival, overall survival was 97.8%. Two-year progression-free survival was at 90%, 34 patients relapsed, and 10 of the men died. Men who did relapse had surgery, chemotherapy, or both as subsequent treatment. There's a prior similar study that was multicenter that had longer follow-up of 5 years, and they reported of ;161 men who had a complete response to the first-line chemo, 10 relapsed (that's 6%) and none died. If we combine these 2 studies together, the bottom line is you would have to perform a post-chemotherapy retroperitoneal dissection, which is a big operation, on about 550 men to prevent potentially at most 44 relapses and 10 deaths. We don't know if we would prevent or how many of those relapses and deaths we would prevent. But there's a lot of operations with a relatively low yield. In the future, we hope to have blood tests that will tell us which men need surgery. And even right now, we're close to the point that we have blood tests that will detect residual cancer. And the chance is we worry about residual cancer in these patients and we don't have the blood test to pick it up. But the bottom line is in the meantime, the preferred management strategy is surveillance rather than surgery for most men. There's some men for whom RPLND may make sense in the center in this setting and some centers that will probably continue to recommend it for most men. I think this data really casts doubt on whether we ought to be doing this operation in these men as a routine practice as opposed to an exceptional practice for men who have particular characteristics. Thank you. Greg Guthrie: Thank you, Dr. Gilligan. And now we can move on to answering some questions. What is the average time expected to see a decline in PSA in patients treated with lutetium-177 PSMA? Dr. Agarwal: I think this a great question and I think we're waiting for the manuscript published to go through the nuances of those data. Right now, what Dr. Michael Morris from Memorial Sloane-Kettering presented were the high-level data on pre-survival and overall survival and some secondary endpoints. We are anxiously waiting the full data in the form of a manuscript. And until then, I will not be able to answer that question. I would like to add that usually the median time, if you look at how -- for how long patients were receiving lutetium, it was 5 to 6 months. If I -- if my recollection is correct. Greg Guthrie: Is radiation required prior to initiating chemo if there's tumor presence? And Dr. Gilligan, you responded. “We rarely use radiation therapy for testicular cancer at this time. Sometimes it is used for stage 1 or stage 2 seminoma as primary treatment instead of chemotherapy.” And I'll just read these aloud for our viewers here. If a patient has both prostate and bladder cancer, how do you decide which therapy should take priority, also, is the CPS typically included on the biopsy report? And Dr. Grivas, you responded, which I'll read here. “This is a bit of a complicated scenario that requires detailed discussion with a urologist and medical oncologist. Regarding CPS, the possible role is only in the first-line setting of metastatic disease to help somewhat decide between chemotherapy followed by avelumab maintenance and immunotherapy. However, it's not a perfect biomarker and not part of the pathology report, it's a special test that requires specific ordering.” I have a question for you, Dr. Zhang. Why do combination treatments seem to work better in kidney cancer? Wouldn't you have more side effects because you're taking 2 drugs at the same time? Dr. Zhang: It's an interesting question. You know, our immunotherapy backbones seem to have good treatment benefit for these immune responsive diseases. The VEGF inhibitors that blocked blood vessel formation for many of our patients with clear cell kidney cancer, they tend to have an immunomodulatory role, so if we normalize blood vessels in the tumor microenvironment, the thought is that the T cells and immune cells can actually get into that space more readily. And so many of these blood vessel blockers are hypothesized to have increased immunomodulatory times of behaviors and the combination actually can be more effective than either agent alone, and we've certainly seen that in practice and really excited to see these combination strategies thrive and be standard of care for our patients now and first-line treatment. For the side effect question, you know, I do think that sometimes we do have to tease out which of the side effects is related to the oral treatment, the blood vessel blocker versus the immune therapy. But it's often experienced oncologists who are able to manage these side effects. We can try to tailor and see which of the side effects is due to which treatment and how to reduce or hold treatments when necessary. Greg Guthrie: Great. I just got a follow-up question for you, Dr. Zhang. Are there any studies for papillary type kidney cancer with sarcoma? Dr. Zhang: I would assume you're asking about sarcomatoid renal cell carcinoma within papillary, so for papillary type of kidney cancers, there are ongoing studies. For example, with FH mutations and FMH loss. For sarcomatoid disease, this is a special type of histology that can occur with any of our actual histologies of kidney cancer. And we know from our phase 3 trials in clear cell sarcomatoid renal cells that these tend to respond to the immunotherapy combinations. And so I would urge using an immune therapy combination in patients who had sarcomatoid renal cell carcinoma. Greg Guthrie: Dr. Agarwal, here is a question for you. There were several studies in here that showed many patients did not receive combination ADT with other novel therapies, which you describe as the standard of care, including the one you discussed. Is this something that patients should proactively bring up with their doctors? Dr. Agarwal: Fantastic question. I'm so glad you asked. The answer is yes: It is our responsibility as physicians and providers, but it doesn't hurt if our patients are educated and challenge us in our decision-making. It is a shared decision-making, it is not the doctor's decision. In my view, it's the patient's decision with help from the doctors. So, yes, please go do it. Doctors usually welcome that. Greg Guthrie: Great. Dr. Grivas: I see one for Dr. Gilligan about surveillance imaging that just popped up. [Is there any data on the benefits vs. risks for imaging based surveillance (CT, MRI, none) for longer-term follow-up periods (e.g. 2+ years)?] Dr. Gilligan: Yeah, they're asking whether there's data on benefit versus risk for imaging-based surveillance and it's actually a very timely question in the sense that we're starting to get data that MRI is very accurate for this. And may likely become a substitute for CT scans at some point in the future. This is something we talk about a lot in terms of surveillance for testicular cancer patients, can we switch to MRI from CT because CT has ionization that can cause other cancers, and MRI does not. The good news is it looks like with current CT scanning, which is lower dose than older CT scanning, the risk of cancer from the CT scan seems really miniscule. Ultimately, it would be great to get it down to 0 and not do them, but we're still doing them. The switch to MRI is being held up by the fact that when you go in and get an imaging study for surveillance, your scans get looked at by a radiologist and also by the oncologist and all of us who do a lot of testicular cancer have multiple stories of catching stuff that the radiologist missed, and they also catch stuff that we miss. It goes both directions, and we're having 2 different people read the films to get a more accurate read. With MRI, most oncologists are not competent to read an MRI well and some radiologists are not great, and the centers where they have excellence have shown that MRIs are just as good as CT scans if read by fully qualified people. And the concern is: are they going to be skillfully read? So the switch to MRI will happen in the future, and I have spoken with people very recently about this that are practicing around the country and the people I talked to were not ready to make the switch because of the concern that stuff might get missed. And I think we can be reassured with the modern lower-dose CT scans, the risk seems to be quite small, and I look forward in the future to making that switch at some point.  Greg Guthrie: And I think that's going to be our last question this afternoon. Thank you to all our participants for sharing this great research with us, as well as your expertise, it's been a real pleasure on this live webinar here. ASCO: Thank you Dr. Agarwal, Dr. Grivas, Dr. Zhang, and Dr. Gilligan.  You can find more research from recent scientific meetings at www.cancer.net. And if this podcast was useful, please take a minute to subscribe, rate, and review the show wherever you listen to podcasts. This Cancer.Net podcast is part of the ASCO Podcast Network. This collection of 9 programs offers insight into the world of cancer care, covering a range of educational, inspirational, and scientific content. You can find all 9 shows, including this one, at podcast.asco.org. Cancer.Net is supported by Conquer Cancer, the ASCO Foundation, which funds breakthrough research for every type of cancer, helping patients everywhere. To help fund Cancer.Net and programs like it, donate at conquer.org/donate. This presentation is provided solely for informational purposes. The ideas and opinions expressed in this presentation do not necessarily reflect the views of the American Society of Clinical Oncology (ASCO) or its affiliates. The mention of any product, service, or therapy in this presentation should not be construed as an endorsement of any product, service, or therapy mentioned. The information herein does not constitute medical or legal advice, and is not intended for use in the diagnosis or treatment of individual conditions or as a substitute for consultation with a licensed medical professional. ASCO assumes no responsibility for any injury or damage to persons or property arising out of or related to any use of the presentation or any errors or omissions. © ASCO 2021, all rights reserved.

The combined clinical cell-cycle risk (CCR) score uses clinical and genetic factors to assess the risk of metastasis after radiation therapy in patients with prostate cancer. The CCR score has proven accurate in studies and can guide post-radiation treatment decisions in practice, according to Jonathan D. Tward, MD, PhD, of the University of Utah, Salt Lake City. Dr. Tward discusses the CCR score with host David Henry, MD, in this episode. About the score The CCR score combines the cell-cycle progression (CCP) score (available commercially as the Prolaris test) and the Cancer of the Prostate Risk Assessment (CAPRA) score to more precisely determine the postradiation risk for metastatic disease. Investigators identified a threshold for determining precise risk levels (2.112), which allows for personalized treatment decision-making based on more individual characteristics than standard risk-group categorizations, according to Dr. Tward. He noted that standard risk groups can include a broad range of actual risk even within a given category. Risk groups are “reasonably good at prognosticating who may or may not go on to have metastasis etc., but they’re not that good,” Dr. Tward said. CCR score proves effective Dr. Tward and colleagues evaluated the CCR score in a retrospective study published in Clinical Genitourinary Cancer (https://bit.ly/3vlgUwe). The study included 718 men with intermediate- or high-risk localized prostate cancer who received single modality or multimodality therapy. Results showed that patients with CCR scores below the identified threshold (2.112) could safely forgo multimodality therapy. CCR score bests other scoring systems In another study, the CCR score proved more accurate than other scoring systems. Dr. Tward presented findings from this study at the 2021 Genitourinary Cancers Symposium (https://bit.ly/3eBvAjM). The study included 741 men with intermediate- or high-risk localized prostate cancer who received single modality or multimodality therapy. The CCR score predicted metastasis (hazard ratio, 2.21; C-index, 0.78) and did so better than National Comprehensive Cancer Network risk groups (C-index, 0.70), the CAPRA score alone (C-index, 0.71), or the CCP score alone (C-index, 0.69). Dr. Tward said he has used the CCR score in his own practice for years and found it helpful. Show notes written by Sharon Worcester, a reporter for MDedge and Medscape. Disclosures Both studies were funded by Myriad Genetics, the company that developed the Prolaris test. Dr. Tward disclosed relationships with Myriad Genetics and other companies. Dr. Henry has no relevant disclosures. *  *  * For more MDedge Podcasts, go to mdedge.com/podcasts Email the show: podcasts@mdedge.com Interact with us on Twitter: @MDedgehemonc David Henry on Twitter: @davidhenrymd 

Proceedings from a webinar held in conjunction with the 2021 Genitourinary Cancers Symposium. Featuring perspectives from Dr Thomas E Hutson and Prof Thomas Powles, moderated by Dr Neil Love.

Proceedings from a webinar held in conjunction with the 2021 Genitourinary Cancers Symposium. Featuring perspectives from Drs Tanya B Dorff, Fred Saad, A Oliver Sartor and Matthew R Smith, moderated by Dr Neil Love.

Proceedings from a webinar held in conjunction with the 2021 Genitourinary Cancers Symposium. Featuring perspectives from Drs Arjun Balar, Elisabeth I Heath and Jonathan E Rosenberg, moderated by Dr Neil Love.

Dr. Sonpavde discusses key data presented during the 2021 Genitourinary Cancers Symposium in urothelial carcinoma and anticipated research directions with immunotherapy, chemotherapy, and antibody-drug conjugates.

This week, we're continuing our coverage of results presented at the 2021 Genitourinary Cancers Symposium, focusing on research findings in renal cell carcinoma and bladder cancer.To listen to more podcasts from ASCO, visit asco.org/podcasts.

The 2021 Genitourinary Cancers Symposium took place virtually from February 11 to 13. This week, we're hearing from three authors of novel research in bladder and kidney cancers.To listen to more podcasts from ASCO, visit asco.org/podcasts.

ASCO: 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 world’s leading professional organization for doctors who care for people with cancer. The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Cancer research discussed in this podcast is ongoing, so clinical trials described here may no longer be enrolling patients, and final results are not yet available.   Before any new cancer treatment can be approved for general use, it must be studied in a clinical trial in order to prove it is safe and effective. In today’s podcast, members of the Cancer.Net Editorial Board discuss 3 clinical trials that are exploring new treatment options across prostate, bladder, and kidney cancer. This podcast will be led by Dr. Timothy Gilligan, Dr. Neeraj Agarwal, Dr. Tian Zhang, and Dr. Brian Shuch. Dr. Gilligan is an Associate Professor and Medical Oncologist at the Cleveland Clinic Taussig Cancer Center. He has no relevant relationships to disclose. Dr. Agarwal directs the Genitourinary Oncology Program at the Huntsman Cancer Institute at the University of Utah. He has served in a consulting or advisory role for Janssen and Bristol-Myers Squibb. Dr. Zhang is an assistant professor of medicine at Duke University School of Medicine and is a medical oncologist at Duke Cancer Institute. She has served in a consulting or advisory role for Janssen and Bristol-Myers Squibb. Dr. Shuch is the director of the Kidney Cancer Program at UCLA Health and the Alvin & Carrie Meinhardt Endowed Chair in Kidney Cancer Research at the institution. He has served in a consulting or advisory role for Bristol-Myers Squibb. View full disclosures for Dr. Gilligan, Dr. Agarwal, Dr. Zhang, and Dr. Shuch  at Cancer.Net. Dr. Gilligan: Hi, I'm Dr. Timothy Gilligan from the Cleveland Clinic Taussig Cancer Institute. I'm joined today by Dr. Neeraj Agarwal from the Huntsman Cancer Institute and the University of Utah and Dr. Tian Zhang from the Duke Cancer Institute and Brian Shuch from the UCLA Institute of Urologic Oncology. Today, we're going to discuss 3 ongoing trials in prostate cancer, bladder cancer, and kidney cancer. As you may know, clinical trial are the way that doctors are able to find better treatment for diseases like cancer. Patient participation is vital for clinical trials. By participating in the clinical trial, you can directly help researchers develop better treatment, reduce side effects, and even reduce the risk of cancer altogether. The 3 trials we'll discuss today were chosen by members of the Cancer.Net Editorial Board Genitourinary Cancers Panel from the trials in progress abstracts that were presented at ASCO 2020 Genitourinary Cancers Symposium. Because these are ongoing clinical trials, final results from these studies are not yet available. I'd like to note that none of us have any direct involvement in any of these trials. To view our full disclosures, please visit the show notes for this episode on Cancer.Net. We're going to start with Dr. Agarwal and a study looking at prostate cancer, the MAGNITUDE trial. [A Study of Niraparib in Combination With Abiraterone Acetate and Prednisone Versus Abiraterone Acetate and Prednisone for Treatment of Participants With Metastatic Prostate Cancer (MAGNITUDE)] Dr. Agarwal, can you tell us a little bit about this study? Dr. Agarwal: This is a large phase III trial of 1,000 patients. This trial includes patients who have progressive, metastatic, castrate-resistant prostate cancer and have never received any other systemic therapy for their castrate-resistant prostate cancer. Dr. Gilligan: Why don't we clarify for listeners what we mean by castrate-resistant prostate cancer? Who are these patients? Dr. Agarwal: When patients present with advanced prostate cancer which has [spread] to different parts of the body, that is called metastatic prostate cancer. And the most effective strategy, which is the backbone of treatment of these patients, is androgen deprivation therapy or castration therapy, which blocks the production of testosterone from the gonads. At this point of time, utilizing medical castration [with drugs] or surgical castration can effectively slow down the progression of cancer. Dr. Gilligan: So these are patients who are already on first-line hormonal therapy to lower their testosterone level? Dr. Agarwal: Yes. Once they start progressing on this first-line castration therapy, we call this state to be castrate-resistant prostate cancer. So this is the patient population which is having disease progression on first-line therapies for the advanced prostate cancer, and now, testosterone levels are low, but still, the prostate cancer is progressing. Dr. Gilligan: So what's the current standard of care for this population of patients who are progressing on first-line hormonal therapy? Dr. Agarwal: In the last 2, 3 years, the treatment of castration-sensitive prostate cancer, which is the newly diagnosed advanced prostate cancer we were just talking about, has changed dramatically. Multiple drugs which are being used, or were being used, in the castrate-resistant prostate cancer have moved to the setting of castration-sensitive prostate cancer. Having said that, many patients with castration-resistant prostate cancer have not yet received any of those drugs. So as an example, in this clinical trial, a patient could have received chemotherapy with docetaxel in the first-line therapy setting or a newly-diagnosed metastatic prostate cancer setting. But then when they have disease progression, the most commonly utilized medications are either abiraterone or enzalutamide, both are oral pills, we call them novel hormonal therapies. So those are still the backbone of treatment for castrate-resistant prostate cancer. Dr. Gilligan: So for patients going on this study, what would the treatment be on the trial? Dr. Agarwal: Patients will be randomized to treatment with abiraterone, which is a novel hormonal therapy, plus prednisone, which is utilized with abiraterone to negate the side effects of abiraterone, plus/minus a new class of drug known as a PARP inhibitor. And in this trial, the drug which is being used is called niraparib. Niraparib is a novel drug, a PARP inhibitor, and just to elaborate a little bit more on PARP inhibitors, this class of drug have recently been approved [to treat patients with] the later phases of castrate-resistant prostate cancer. So 2 drugs, olaparib and rucaparib, were recently approved by FDA in those patients who have had disease progression on novel hormonal therapy plus/minus docetaxel chemotherapy, so for pretty late phases of prostate cancer or castrate-resistant prostate cancer. In this trial, a PARP inhibitor is being moved upstream so that patients don't have to wait for disease progression or novel hormonal therapy or chemotherapy in metastatic castrate-resistant prostate cancer, and they will have the availability of this drug upfront in this setting of newly diagnosed metastatic castrate-resistant prostate cancer. Dr. Gilligan: When this drug is used in the more advanced setting, it's limited to patients who have particular mutations. Is that the case in this study as well? Dr. Agarwal: This trial is targeting the strategy to 2 different patient populations. So 1 patient population is that [in which the] tumor has defects or mutations in the DNA repair genes. We call them homologous recombination repair mutations. I put it simply, DNA repair gene mutations. So there is a cohort of patients, a group of patients, among these 1,000 patients, who will harbor DNA repair gene-related defects in the tumors. And there is another cohort of patients who do not have to have those defects, and we call them unselected patients. This trial is enrolling both groups of patients, and, in fact, the patients' unselected cohort has actually completed accrual. So the trial is now only looking at those patients who are harboring DNA repair gene-related defects in the tumors. Just to complete the story in this context, as you said, the drugs olaparib and rucaparib, which have already been approved in the later phases of castrate-resistant prostate cancer, they are only approved for patients who are harboring DNA repair defects. Dr. Gilligan: So for the patients who can go on the trial now, who have these defects, the question this trial is asking then is, does it help to use this treatment earlier on rather than waiting until later? Dr. Agarwal: Absolutely. So given these are oral therapies, reasonably well tolerated, better tolerated than traditional chemotherapies, it makes sense to move these oral pills to upfront or earlier settings where more patients can be candidates for these drugs which can be taken at home, and these patients don't have to have disease progression on chemotherapy to [receive] these medications. Just to complete, Tim, I just want to add that there are 2 endpoints of this trial. One is radiographic progression-free survival, which is the primary endpoint, and the secondary endpoint is overall survival and many other endpoints we'd like to see, like pain progression or toxicities and so on. Radiographic progression-free survival means how long these drugs or drug combination is able to contain the disease from progressing [or worsening] as detected by the scans. We hope that this trial will show delayed progression on the novel combination compared to abiraterone. Dr. Gilligan: Thank you. So one last question, are there any known risks that patients should be aware of? What are the side effects of this class of medication? Dr. Agarwal: Yes. Two major side effects. Every drug has side effect. And so do niraparib and abiraterone. So abiraterone is already approved for patients with metastatic castrate-resistant and castration-sensitive prostate cancer. So I'm not going to elaborate much on abiraterone. Regarding niraparib, this class of drug, including olaparib and rucaparib which I earlier mentioned, they have this class of side effects, which belong to this class of drugs. And 1 of the most common side effects is anemia, which is low hemoglobin, and which happens because these drugs can also slow down the replication of red [blood] cells. Other less common side effects are decrease in the platelet counts and decrease in the white cell counts. But they happen with much lesser degree compared to anemia. Another common side effect is nausea. Nausea and vomiting can happen, and we have to keep an eye on nausea and vomiting because the side effect can easily be prevented or treated with anti-nausea medications. There are many other side effects which are less common, and I won't get into them, but these are the 2 most common side effects, which are fortunately easy to handle in the clinic. Dr. Gilligan: And I just want to repeat what you said before that there is accrual still going on for the study, but it's limited to patients who have particular mutations in their cancers. Dr. Agarwal: Yes. So currently the study is not accruing for those patients who do not have those DNA repair general-related events. But it is still accruing patients, looking for patients who are known to have those mutations in the prostate cancer. Dr. Gilligan: What proportion of patients with prostate cancer have these kinds of mutations? Dr. Agarwal: Depending upon the study, I would say up to 20% of patients can have DNA repair gene-related defects in their tumors. So it is very important to bring this up with our clinical or medical oncologists who are treating patients with metastatic or advanced prostate cancer, and especially with approval of 2 drugs, it is very important that every single patient who is deemed to be a candidate for treatment with this class of drug, PARP inhibitor, undergoes comprehensive genomic profiling or simply speaking, mutation testing of their prostate cancer tumors. Dr. Gilligan: Thank you. And I think that's worth emphasizing. This is an example of personalized cancer care based on the genomics of the individual's tumor which is happening more and more, and as Dr. Agarwal said, if you have metastatic prostate cancer, we are recommending a standard of care that people get genomic testing now. So this is an example of a step in that direction. So thank you, Dr. Agarwal. Dr. Zhang, why don't we move on and talk about the bladder cancer trial that you were going to discuss, the PROOF 302, that also has a personalized genomic component to it, I believe. [Study of Oral Infigratinib for the Adjuvant Treatment of Subjects With Invasive Urothelial Carcinoma With Susceptible FGFR3 Genetic Alterations] Dr. Zhang: In bladder cancer, we've come to a place where the genomic profiling is very important to find FGFR mutations or fusions, and this subset of patients that have FGFR mutations or fusions, these patients tend to have good responses to now standard of care treatments in the metastatic setting. And this particular trial is looking at using a drug called infigratinib in this patient population, specifically targeting that FGFR and inhibiting it. This is a trial in the adjuvant setting for patients who have urothelial cancer of either the bladder or of the ureters and upper tract who received surgery and then go onto this trial or treatment with infigratinib versus a placebo. Dr. Gilligan: Can you spell out for our listeners who the group of patients are who are going to be eligible for the study? Dr. Zhang: Sure. These are patients who have already undergone surgery for either their bladder cancer or an upper tract tumor. And so these are patients in that 4-month window after surgery, who have already had their surgeries, and it's either for patients who have had prior chemotherapy before their surgeries or not with higher-risk features defined based on each of those populations. But it is for a higher-risk patient population that have a higher risk for having disease recurrence and spread of their urothelial cancers after surgery. In this setting, we really don't have any approved adjuvant treatments. And so the point of this study is really to try to prevent disease recurrence. Dr. Gilligan: I want to clarify 1 thing. My understanding was for these patients who have not had preoperative chemotherapy, they are not patients who were considered eligible for postoperative cisplatin-based chemotherapy since that is often used in the adjuvant setting. Is that correct? Dr. Zhang: That's absolutely correct, Tim, and thanks for pointing that out. So if patients had not received preoperative chemotherapy, they have to be ineligible for cisplatin-based chemotherapy, which we would often recommend in the postoperative setting. But if they are not eligible for chemotherapy after surgery and have these higher-risk features, then they would qualify for this study. Dr. Gilligan: I think it's important for patients to understand that because if considering going on this trial, the standard of care would be just to watch. And so what it's asking is, can we do something instead of just watching that would lower the risk of relapse or worse outcome with the cancer? Dr. Zhang: Absolutely. I think we always try to recommend proven strategies first, and in this particular case, the recommendation for somebody who is a candidate for chemotherapy after surgery would still be to go with chemo first. Dr. Gilligan: The genetic testing that will be done to determine eligibility for the study, can you say a little bit more about that? Dr. Zhang: Sure. My understanding is that the study will take most genomic tests that are currently commercially available, but they have to fulfill the criteria of having FGFR mutations and/or fusions in the tumor in order to go on the study. So we often now will send the surgical specimens for genomic testing, especially in our higher-risk patients that are defined like the study defines. And so that particular patient population, because they're at higher risk for recurrence, we try to identify these FGFR mutations and fusions early on so that we can know whether the standard treatment for these patients would be an option later on. Dr. Gilligan: Are there cost implications of that for the patients? Dr. Zhang: Certainly, now some of the commercially available genomic testings are approved by insurance and are billable through insurance, but patients may be responsible for a copay. I want to add 1 more thing about the drug itself because I do think there's some interesting activity of infigratinib that has been published in the last year, and that is in the earlier-phase studies of infigratinib in the metastatic setting, in the more advanced urothelial cancer settings, we saw pretty high response rates as well as disease control rates, particularly in patients who had disease in the upper tracts, so in the ureters and above. And so I think it's promising and potentially very interesting to study this for patients who have had disease removal, and surgeries. Dr. Gilligan: That's an important point for listeners to understand, that this is an exciting new class of drugs and in patients for whom this treatment is appropriate, we're seeing very good response rates in more advanced disease settings, and there's a natural progression. When we see it work in the advanced setting, we try to move it to an earlier setting to see if we see a similar or greater benefit. As Dr. Agarwal was saying about prostate cancer, we've found a number of times that using drugs earlier works better. This is another example of studying that to see if that's the case here. Dr. Zhang: I absolutely agree. Dr. Gilligan: What should listeners know about potential risks or side effects for this class of treatment? Dr. Zhang: FGFR inhibitors like infigratinib have a class effect, and I think the main toxicities that we've come to see are skin toxicities and nail toxicities, as well as there are some eye toxicities as well. So particularly for patients who are going on these types of treatments, we often will recommend baseline eye exams, and then to follow them on treatment, particularly for any blurry vision or other vision changes that arise. And 1 of the class effects of these FGFR inhibitors is also to cause increases in phosphorus levels [in the blood], and that is due to their inhibition in the renal tubules to prevent phosphorus excretion. And so there was a recent publication also that for patients who develop high phosphorus levels, while getting infigratinib or these FGFR inhibitors, that these patients actually have potentially a higher response rate as well. So I think that has to be proven more in these bigger trials, but it's an interesting biomarker potentially for patients who might have good responses. Dr. Gilligan: So for patients who had urothelial cancer resected or at high risk for relapse, this is an exciting new option for them, if they have the right genomic composition of the cancer and would not otherwise receive chemotherapy. So thank you for the summary. Okay. So now we're going to talk about kidney cancer and the CYTOSHRINK discussion. [SBRT With Combination Ipilimumab/Nivolumab for Metastatic Kidney Cancer (CYTOSHRINK)] And we have Dr. Brian Shuch with us to discuss that. Brian, can we start off with who this study is designed for? Dr. Shuch: It's really designed for patients with metastatic kidney cancer. Could be any type of kidney cancer, presenting with metastatic disease. We call that de novo metastatic disease. So they would have their primary tumor still in place in their kidney, with disease outside of that organ in other locations. Dr. Gilligan: So these are patients with-- they have the tumor in their kidney, it's spread somewhere else, and they haven't had any other treatment so far? They haven't had any surgery or any drugs? Dr. Shuch: Correct. These will be patients that are treatment-naïve that are going to start on their first course of treatment, which, in general, would be a discussion of either surgery or systemic therapy. Dr. Gilligan: So at this point in time, what's the standard of care for such patients? Dr. Shuch: We used to take every patient to surgery upfront. We call that a cytoreductive nephrectomy. Since we've had much better agents in recent years, and these agents have a lot of activity, we've done less upfront surgery as it appears that some patients may not benefit from racing off to the OR. So these are patients that generally would get started on systemic therapy first because this population, and this trial, has some risk factors for worse disease. We call that intermediate- or poor-risk features. Dr. Gilligan: So these are patients who we would not normally do surgery on because it doesn't seem to help them, unlike some of the other patients who we do, the good-risk patients. Dr. Shuch: Well, we are investigating that in other trials, but there are plenty of patients who are not going to run right to surgery, and these are the ones that we would consider deferring surgical management of the primary tumor. We would get started on systemic therapy, and we would reassess how they would be [treated] in the future, whether surgery was an option. But there are emerging entities such as radiation, which we'll discuss, which could be another exciting approach. Dr. Gilligan: So if a patient that was going to go on this trial didn't go on the trial, they would most likely be treated with medications at this point in time. Is that correct? Dr. Shuch: Correct. There'd be standard medications which are available off clinical trial which are right now dual therapy with 2 immune agents, or an immune agent and a tyrosine kinase inhibitor. So these are standard drugs that are available off a trial. Patients get started on therapy, and we see how they do later for other treatment options. Dr. Gilligan: So what is this study looking at? What's the new thing that it's introducing and the question that it's asking? Dr. Shuch: So kidney cancer, 10, 15 years ago, there was never really any role for radiation except for very rare circumstances. But now we have newer types of radiation where we're doing radiation at much higher doses in shorter time periods, and we call that ablative dosing. And as we've used that in brain and bone lesions for kidney tumors, and with excellent efficacy, with great—what we call local control. That has been applied to the primary tumor as well, and that's been used in many fields, that type of alternative radiation approach. We call that stereotactic radiation or the term radiosurgery, which is really a misnomer. It's just high dose ablative radiation, and it can be used in the primary tumor as a way maybe to kill the tumor. Dr. Gilligan: And what is that outcome that we're hoping for? How would success be measured if this trial is positive? Dr. Shuch: Well, we do know for small tumors, it seems to be a fairly effective measure at stopping tumors from growing. In this situation, it's employed after initiation of systemic therapy. Half the patients will get this radiation therapy to that primary kidney tumor, and the goal is to see if it delays progression of the disease. What we call progression is generally growth of lesions that are existing, or development of new lesions, new spots around the body. So the goal is to see if radiation with the standard immune therapy would delay progression versus the standard immune therapy alone. Dr. Gilligan: So just to reiterate then, I guess for patients who are on this trial, normally they would get treated just with the immunotherapy or combined immunotherapy and targeted therapy, and what we're asking here is, if we give them radiation too, do they do better? Do we delay progression of disease? That we keep things under control longer, that they live longer? Dr. Shuch: Correct. Obviously, living longer is a major factor. That's another objective of the study, but the study doesn't have enough patients or enough power to kind of detect that. The real issue is, does it delay the progression? And progression is important because if you have progression, often patients will progress to another line of therapy, meaning disease is not under good control. Dr. Gilligan: Are there any known risks from the radiation therapy the patient should be aware of? Dr. Shuch: Depending on the size of the tumor and the location to other organs, radiation could have some local effects. Obviously, there's some potential damage to surrounding structures such as the skin. There's some radiation that potentially could stray into other surrounding organs like the duodenum on the right side or the liver, the colon, small bowel, the ureter. And those organs generally can have some degree of toxicity. Generally, it's self-limiting with minor long-term effects, but we haven't done this for many, many years because it's a newer emerging modality. We do believe it's safe with large studies of smaller tumors, but patients do need to be aware that there could be some local irritation from radiation. Dr. Gilligan: Is this trial still open to patients? Dr. Shuch: So this is a trial based out of Canada by 1 of their cooperative groups in Ontario. It's a small study - only 78 patients - that opened this year. In discussion with the investigators, this study is accruing well, but it is anticipated to be open for another year. Because they're looking at what's called progression-free survival, we're hoping we can have results of this study within the next 2 years. Obviously, it is something open only to Canadian residents right now, but I will tell you that there are other groups in the U.S. that are considering similar types of trials in the Cooperative Group Network. Dr. Gilligan: There's 1 final point I wanted to give you an opportunity to clarify for our listeners who may not be familiar with the idea of cytoreductive nephrectomy or cytoreductive treatment. So this is a treatment where we are targeting the primary tumor, even though there's other cancer elsewhere in the body that we can't remove. Can you just talk a little bit about the rationale for that, and why we're doing that? Dr. Shuch: Historically in kidney cancer, when we had no effective therapy, we would have this phenomena: we removed the big bulky tumor, and 1% to 2% of patients would have their distant sites shrink, okay? And whether that was related to an immunologic phenomenon, maybe the tumor was secreting something, or maybe it was just overwhelming the body's defense mechanisms because they had a big tumor making them sick, it was kind of unclear. But we did know in larger trials with immune therapy, when we gave immune therapy in the old days, the agents like interferon-alpha or IL-2, we gave these agents, the primary tumor wouldn't shrink. Sometimes the distant sites could shrink, but it would not lead to what we call complete responses. So anyone who wanted to have a home run therapy where it was hoping to cure them, they would have their primary tumor removed first, and then they would potentially have the systemic immunotherapy. We've done 2 trials which showed, early in the 90s, that if you were able to remove the primary tumor and treat with these older immune agents, patients would have better outcome. And as those agents were pretty ineffective, we thought the survival benefit was really due to removing the big bulky primary. So the rationale for this trial is, you're not removing the big bulky primary tumor, you're potentially killing it with radiation, so you're overall reducing the burden of disease. There are some theoretical benefits of radiation where you kill tumors, and the tumors release what we call antigens. Basically, I try to explain that to people it's basically like a patch. Like a Boy Scout or Girl Scout has a new patch on them, and you'd recognize them as maybe having a badge of like hunting. So the tumor potentially might expose some of these bad patches, and the immune system might wake up and recognize them, and hopefully, then attack other sites of disease. So, again, the goal is either you're reducing the overall burden of disease in the body, or you're maybe allowing the body's immune system to kick in because you're killing a [tumor] there. We're just not sure really the mechanism, but it's been long used in kidney cancer, this idea of reducing the burden of disease. Dr. Gilligan: Thank you for listening to this podcast. There are many different clinical trials currently enrolling people with genitourinary cancers. If you're wondering whether participating in a clinical trial might be right for you, please talk to your health care team. ASCO: Thank you, Drs. Gilligan, Agarwal, Zhang, and Shuch. Visit www.cancer.net/clinicaltrials to learn more about participating in clinical trials. All treatments have side effects—please talk to your health care team about possible side effects to watch out for. And if this podcast was useful, please take a minute to subscribe, rate, and review the show on Apple Podcasts or Google Play. This Cancer.Net podcast is part of the ASCO Podcast Network. This collection of 9 programs offers insight into the world of cancer care, covering a range of educational, inspirational, and scientific content. You can find all 9 shows, including this one, at podcast.asco.org. Cancer.Net is supported by Conquer Cancer, the ASCO Foundation, which funds breakthrough research for every type of cancer, helping patients everywhere. To help fund Cancer.Net and programs like it, donate at conquer.org/donate.

Cleveland Clinic Cancer Center oncologist Shilpa Gupta, MD discusses promising findings in the treatment of advanced bladder cancer in this week's Cancer Advances podcast. Dr. Gupta shares data from the phase II Bladder Cancer Signal Seeking Trial (BLASST-1), recently presented at the American Society of Clinical Oncology’s Genitourinary Cancers Symposium. She also provides an update on additional in-progress clinical trials and what’s on the horizon for bladder cancer research.

ASCO: 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 world’s leading professional organization for doctors who care for people with cancer. The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Cancer research discussed in this podcast is ongoing, so clinical trials described here may no longer be enrolling patients, and final results are not yet available.   Before any new cancer treatment can be approved for general use, it must be studied in a clinical trial in order to prove it is safe and effective. In today’s podcast, members of the Cancer.Net Editorial Board discuss 3 clinical trials that are exploring new treatment options across prostate, germ cell, and kidney cancer. This podcast will be led by Dr. Sumanta (Monty) Pal, Dr. Neeraj Agarwal, Dr. Timothy Gilligan, and Dr. Tian Zhang. Dr. Pal is co-director of City of Hope's Kidney Cancer Program and is the head of the kidney and bladder cancer disease team at the institution. He has served in a consulting or advisory role for Astellas Pharma, and Bristol-Myers Squibb. Dr. Agarwal directs the Genitourinary Oncology Program at the Huntsman Cancer Institute at the University of Utah. He has served in a consulting or advisory role for Astellas Pharma, Bristol-Myers Squibb, Nektar Therapeutics, and Merck. Dr. Gilligan is an Associate Professor and Medical Oncologist at the Cleveland Clinic Taussig Cancer Center. He has no relevant relationships to disclose. Dr. Zhang is an assistant professor of medicine at Duke University School of Medicine and is a medical oncologist at Duke Cancer Institute. She has served in a consulting or advisory role for Bristol-Myers Squibb and Merck. View full disclosures for Dr. Pal, Dr. Agarwal, Dr. Gilligan, and Dr. Zhang at Cancer.Net. Dr. Pal: Hi. I'm Dr. Monty Pal from the City of Hope. I'm joined today by Dr. Neeraj Agarwal from the Huntsman Cancer Institute and University of Utah, Dr. Timothy Gilligan from the Cleveland Clinic Taussig Cancer Institute, and Dr. Tian Zhang from Duke Cancer Institute. Today we're going to discuss 3 ongoing clinical trials in prostate, germ cell, and kidney cancer. As you may know, clinical trials are the main way that doctors are able to find better treatment for diseases like cancer. Patient participation is vital for clinical trials. By participating in a clinical trial, you can directly help researchers develop better treatment, reduce side effects, and even reduce the risk of cancer altogether. The 3 trials we'll discuss today were chosen by members of the Cancer.Net Editorial Board Genitourinary Cancers Panel from the trials in progress abstracts that were presented at ASCO's 2020 Genitourinary Cancers Symposium. Because these are ongoing clinical trials, final results from these studies are not available yet. I'd like to note that none of us have any direct involvement with any of these trials. To view our full disclosures, please visit the show notes for the episode on Cancer.Net. Now, the first trial we're going to discuss is the KEYNOTE-641 trial for prostate cancer.  [Study of Pembrolizumab (MK-3475) Plus Enzalutamide Versus Placebo Plus Enzalutamide in Participants With Metastatic Castration-resistant Prostate Cancer (mCRPC) (MK-3475-641/KEYNOTE-641)] Dr. Agarwal, can you tell us who this study is designed for? Dr. Agarwal: This trial is designed for patients with advanced prostate cancer, or metastatic prostate cancer, who are experiencing disease progression on standard androgen deprivation therapy, a state known as castrate resistant prostate cancer. Dr. Pal: And if you see these patients in your clinic right now, what is the current standard of care? Dr. Agarwal: The most commonly utilized [treatments for] these patients include drugs which block androgen signaling inside the prostate cancer cell. And one of the most commonly utilized drugs is enzalutamide followed by abiraterone. Dr. Pal: Tell us a little bit about how this particular study aims to improve or change the current standard of care. Dr. Agarwal: Early clinical data showed that adding the immunotherapy agent pembrolizumab to enzalutamide may improve survival outcomes. The response rates in that smaller study were meaningful and were very promising. Based on those earlier data, this trial has been designed and is asking two main questions. Number one, whether adding the immunotherapy agent pembrolizumab to enzalutamide will improve overall survival. And the second question is, whether adding pembrolizumab to enzalutamide will delay disease progression. Dr. Pal: Are there any risks that patients should be aware of with this regimen? Dr. Agarwal: Both agents are very commonly utilized for many years now in oncology clinics. Enzalutamide is an oral pill which blocks androgen signaling and is associated with side effects such as fatigue, muscle loss, bone loss, falls, and many others which are relatively easy to manage over time. Pembrolizumab is an intravenous therapy approved for multiple cancer types, and is associated with immune-related side effects. Many of these can be severe in 4 to 5 percent of patients receiving pembrolizumab. These can include diarrhea, abnormal liver function tests, or liver toxicity, a skin rash, lung toxicity, which can include pneumonitis [or lung inflammation]. But most of these side effects can be managed as long as they are promptly detected. So I think education and close monitoring with oncologists is the key for early prevention and management of the side effects. Dr. Pal: Those are great tenets, not just for this clinical trial but in using these agents in general. Thanks a lot. And final question for you, Dr. Agarwal. Is this trial still open right now? And if so, when do you think we might see some results from it? Dr. Agarwal: This trial is open across the United States and different parts of the world. And the primary results, early results, will be available, I'm hoping, in 2023, in the middle of 2023. Dr. Pal: Well thank you for that excellent overview, Dr. Agarwal. I'm going to turn my attention now to Dr. Gilligan to discuss a topic that we don't often have on this podcast. But this is nonetheless a critical disease space for us to discuss. Dr. Gilligan is going to tell us about the P3BEP clinical trial in testicular cancer. [Accelerated v's Standard BEP Chemotherapy for Patients With Intermediate and Poor-risk Metastatic Germ Cell Tumours (P3BEP)] Dr. Gilligan, can you tell us a little bit about who this study is designed for? Dr. Gilligan: Yes, germ cell tumors are cancers that start in the reproductive cells, most commonly in testicles of adolescent or adult men. But germ cell tumors can also start in children - typically not in the testicles but elsewhere in the body - and they can start in women in the ovaries or elsewhere. In children, we sometimes see [germ cell tumors starting in the brain]. Those are not included in this trial. But basically, everybody else with germ cell tumors are eligible for this - men, women, and children - if they have a poor or intermediate prognosis. And just to clarify one more piece about that, this is for people who have advanced stage disease. Again, men, women, or children with advanced stage metastatic germ cell tumors, as long as it didn't start in the brain. And as long as their prognosis is in the intermediate or poor risk category, not the good risk category. Dr. Pal: So glad that you pointed that out, Tim. I have to tell you that I gave this incorrect label of a testicular cancer study, but critical for our listenership to know the germ cell tumors can occur both in males and females. Can you tell us a little bit about the current standard of care for the patients that are being [included] in this study? Dr. Gilligan: Absolutely. Chemotherapy for germ cell tumors has been one of the huge success stories of modern oncology, and the cure rate is extremely high. Overall, [we cure about 96% of men with testis cancer.] However, when you start to look at advanced stage disease in intermediate and poor risk patients, the success rate goes down. It's about a 75% cure rate for patients with intermediate risk tumors and 60% for [those with] poor risk tumors. The standard of care has been the same for a long time. It's 4 cycles of chemotherapy called BEP, and that's what has produced those results. And while those results are good, we would like them to be a lot better. Dr. Pal: So Dr. Gilligan, you've used this term intermediate and poor risk in the context of patients with germ cell tumor. Can you tell us a little bit about what intermediate and poor risk [means]? Dr. Gilligan: Yes, it's based mostly on where the cancer has spread to and how high certain blood tests are. There are things called tumor markers which are proteins in the blood that are made by the cancer, and the higher those levels, the worse the prognosis. Similarly, if the cancer has spread to certain organs, such as the liver or the bones or the brain, organs other than the lungs, then patients have a poorer outcome and a poorer prognosis. The last category is men and women who have certain germ cell tumors that grow in the chest called extragonadal tumors. They also have a prognosis that's not as good as other germ cell tumors. So it's a little bit complicated, and for patients, when you see your oncologist, they can clearly tell you which prognostic category you fall into. Dr. Pal: How does this study aim to improve or change the standard of care? Dr. Gilligan: So mainly we'd like to get those numbers better. And I think the key idea in this study is that with chemotherapy, which is different than the kinds of drugs we talked about in the prior conversation, the philosophy is to basically give patients as much of a dose as they can safely tolerate. And the idea of this trial is that if we give the chemotherapy more frequently - if we kind of squeeze together the cycles so that rather than every 3 weeks we're repeating it every 2 weeks - can we get a better response in killing the cancer without having too much toxicity? Dr. Pal: So they use this term in the title “accelerated.” Is that what you're referring to there? Dr. Gilligan: Yes. So if you think of chemotherapy as something that is repeated, we're repeating it sooner. And we used to give the patient 3 weeks to recover. On this trial, they're comparing that standard approach every 3 weeks to giving it every 2 weeks. In other words, we're making it denser. You get the chemotherapy faster. And the question is, will we cure more people that way or not? Dr. Pal: And Dr. Gilligan, any known risks that patients should be aware of as they [consider] a study like this? Dr. Gilligan: Well I think the risk with this approach is that we may increase toxicity without improving outcomes. Past attempts to do better than the standard treatment have not been successful. And the current standard treatment has been the standard for a long time as a result. We are hoping the new approach will be better, but we don't know until we try it, and it's possible that it will be more toxic. Dr. Pal: When do you think we might see some results from this? Dr. Gilligan: I don't know when we will see results. My guess is that it will be within a few years. Germ cell tumors grow quickly; they're aggressive cancers, so you tend to get your results pretty quickly, but I don't know exactly. Dr. Pal: Dr. Gilligan, thank you for that excellent overview. Last, but certainly not least, we're going to turn our attention to Dr. Tian Zhang for discussion of a very important study in kidney cancer. [A Study of Bempegaldesleukin (NKTR-214: BEMPEG) in Combination With Nivolumab Compared With the Investigator's Choice of a Tyrosine Kinase Inhibitor (TKI) Therapy (Either Sunitinib or Cabozantinib Monotherapy) for Advanced Metastatic Renal Cell Carcinoma (RCC)] Tell us a little bit about this study and who it's designed for. Dr. Zhang: PIVOT-09 is a study of a combination of a [novel] immunotherapy called bempegaldesleukin in combination with nivolumab compared to investigator-selected sunitinib or cabozantinib. So these are standard blood vessel blockers. The study is designed for patients with metastatic clear cell kidney cancer who have had no prior medication treatments and also measurable disease that can be followed on subsequent scans. Dr. Pal: And when you're seeing these patients in clinic with metastatic kidney cancer, what is the current standard of care? What are you using to treat patients these days? Dr. Zhang: We've known for a long time that kidney cancer will respond to these immune activating therapies, and [it has been demonstrated that a drug called IL-2, when given in high doses,] improved the overall survival for a subset of patients with metastatic kidney cancer and [produced] really durable complete responses for a small number of patients. However, it was highly, highly toxic, and there were lots of patients who ended up in the hospital. It had significant toxicities and patients were treated in the hospital for about a week at a time. So since about 2018, our standard of care immunotherapy options [have included] agents like ipilimumab and avelumab or the combination of pembrolizumab or avelumab with a blood vessel blocking agent. This is an easier way to give immune activating treatments in a more targeted fashion. [With this study we are testing] whether the IL-2 cytokine can be modified and given more in a more safe and effective manner. Dr. Pal: This is an interesting drug. If I understand it correctly, we're taking IL-2 from yesteryear, a drug that we used more than a decade ago to treat patients with advanced kidney cancer, and we're retooling it a bit for patients to really enhance the efficacy, maybe really enhance the safety of the compound as well. Can you tell us how this compound's doing that? Dr. Zhang: Right so bempegaldesleukin is a special formulation of IL-2. It's actually a pegylated form of the IL-2 cytokine, so it includes this polyethylene glycol molecule around the IL-2. And this pegylation allows that cytokine to be released slowly [in the bloodstream] so that in itself may improve the side effect profile. And then it also activates the tumor fighting subset of immune cells, T cells and natural killer cells in the tumor microenvironment, without activating other suppressive T cells. So the thought from preclinical studies is that bempegaldesleukin, because of its pegylated form, will actually decrease the side effects while activating the tumor fighting cells in the tumor microenvironment. Dr. Pal: And in this trial, how will success be evaluated? How will we know the treatment is working, that it's positive? Dr. Zhang: So the primary objective for this particular trial is a composite of objective responses as well as overall survival, and then secondary objectives include progression free survival - so lengthening time until disease progression - as well as evaluating the safety of the combination and the quality of life for patients who are treated on this combination. Dr. Pal: Now I remember IL-2, the drug that you referred to, from more than a decade ago, giving it to patients and certainly it came with a lot of toxicity. What are some of the toxicities of patients receiving bempegaldesleukin should be aware of? Dr. Zhang: Some of the early phase 1 trials that evaluated bempegaldesleukin found that some of the toxicities included low blood pressure as well as syncope where patients would feel lightheaded [or faint,] headaches, edema, swelling in their legs and fluid buildup, as well as infusion reactions. And I think we should also think about the immunotherapy-related toxicities of nivolumab where we're giving it in combination. So diarrhea, rashes, endocrine dysfunction are pretty common. So those would be some of the expected side effects of the immunotherapy cohort. And then we shouldn't forget about the control cohort treated with standard sunitinib or cabozantinib, and those side effects would include hypertension, hand foot syndrome or other rashes, diarrhea, nausea, hypothyroidism, and loss of protein in the urine. Dr. Pal: Right. Well a final question for you Dr. Zhang. Is this trial still open to patients, and if it is, when do you think we might see some results from it? Dr. Zhang: Yes, the trial is still open. It's enrolling up to 600 patients total and it's currently open globally in the U.S., Mexico, South America, Asia, Russia, and Australia. I'm hoping we will see results from this phase 3 trial in the next 2 to 3 years. Dr. Pal: Well thank you very much, Dr. Zhang, Dr. Gilligan, Dr. Agarwal. There are many different clinical trials currently enrolling people with genitourinary cancers. If you're wondering whether participating in a clinical trial might be right for you, please talk to your health care team. Thanks so much for listening. ASCO: Thank you, Drs. Pal, Agarwal, Gilligan, and Zhang. Visit www.cancer.net/clinicaltrials to learn more about participating in clinical trials. All treatments have side effects—please talk to your health care team about possible side effects to watch out for. And if this podcast was useful, please take a minute to subscribe, rate, and review the show on Apple Podcasts or Google Play. This Cancer.Net podcast is part of the ASCO Podcast Network. This collection of 9 programs offers insight into the world of cancer care, covering a range of educational, inspirational, and scientific content. You can find all 9 shows, including this one, at podcast.asco.org. Cancer.Net is supported by Conquer Cancer, the ASCO Foundation, which funds breakthrough research for every type of cancer, helping patients everywhere. To help fund Cancer.Net and programs like it, donate at conquer.org/donate.

ASCO: 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 world’s leading professional organization for doctors who care for people with cancer. The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Cancer research discussed in this podcast is ongoing, so clinical trials described here may no longer be enrolling patients, and final results are not yet available.   Before any new cancer treatment can be approved for general use, it must be studied in a clinical trial in order to prove it is safe and effective. In today’s podcast, members of the Cancer.Net Editorial Board discuss 3 clinical trials that are exploring new treatment options across prostate, bladder, and kidney cancer. This podcast will be led by Dr. Timothy Gilligan, Dr. Sumanta (Monty) Pal, Dr. Petros Grivas, and Dr. Tian Zhang. Dr. Gilligan is an Associate Professor and Medical Oncologist at the Cleveland Clinic Taussig Cancer Center. He has no relevant relationships to disclose. Dr. Pal is co-director of City of Hope's Kidney Cancer Program and is the head of the kidney and bladder cancer disease team at the institution. He has served in a consulting or advisory role for Astellas Pharma, Exelixis, and Pfizer. Dr. Grivas is the clinical director of the Genitourinary Cancers Program at University of Washington Medicine. He is also an associate member of the clinical research division at the Fred Hutchinson Cancer Research Center. He has served in a consulting or advisory role for Exelixis, Merck, and Pfizer. Dr. Zhang is an assistant professor of medicine at Duke University School of Medicine and is a medical oncologist at Duke Cancer Institute. She has served in a consulting or advisory role for Exelixis, Merck, and Pfizer. View full disclosures for Dr. Gilligan, Dr. Pal, Dr. Grivas, and Dr. Zhang at Cancer.Net. Dr. Gilligan: Hi. I'm Dr. Timothy Gilligan from the Cleveland Clinic. I'm joined today by Dr. Monty Pal from the City of Hope Cancer Center, Dr. Petros Grivas from the Fred Hutchinson Cancer Research Center and University of Washington, and Dr. Tian Zhang from Duke Cancer Institute. Today, we're going to discuss three ongoing clinical trials in prostate, bladder, and kidney cancer. As you may know, clinical trials are the main way the doctors are able to find better treatment for cancer and other diseases. Patient participation is vital for clinical trials. By participating in a clinical trial, you can directly help researchers develop better treatment, reduce side effects, or even reduce the risk of cancer all together. The three trials we'll discuss today were chosen by members of the Cancer.Net Editorial Board Genitourinary Cancers Panel from the trials and progress abstracts that were presented at ASCO's 2020 Genitourinary Cancers Symposium. Because these are ongoing clinical trials, final results from these studies are not available yet. I'd like to note that none of us have any direct involvement with any of these trials. To view our full disclosures, please visit the show notes for this episode on Cancer.Net. So to get started, the first study we'll discuss is the TALAPRO-2 trial for prostate cancer, [Talazoparib + Enzalutamide vs. Enzalutamide Monotherapy in mCRPC (TALAPRO-2)] and Dr. Pal is going to discuss this. So if we could get started, just to begin with, who is the study designed for? Dr. Pal: Thanks a lot, Dr. Gilligan. Well, this study addresses a unique disease population. It's patients with prostate cancer that's metastatic, and that implies that the cancer has migrated out of the prostate to other organs. But beyond that, it also implies that these patients have also developed some resistance to first line hormone treatment. So patients in this study [have] so-called hormone resistant or castration resistant [prostate cancer]. Dr. Gilligan: So if a patient was in this situation, and they weren't going on this trial, what would be the standard treatment for them at this time? Dr. Pal: There are several options for these patients. Hormone therapies like abiraterone and enzalutamide could be considered. Chemotherapy is also a consideration. Dr. Gilligan: And can you say a little bit more about what the patients would receive if they went on it? The subjects of the study, what they'll get? Dr. Pal: Some patients with prostate cancer may have [a deficiency in their cancer’s ability to repair damage to DNA]. This is something that we've seen in other tumor types, breast cancer perhaps being the most notable example. Pancreatic cancer being another one. In this particular trial, [the researchers] try to exploit that by using a class of drugs called PARP inhibitors. In this case, a drug called talazoparib. So patients in this study receive a standard hormone therapy called enzalutamide. And they receive that with or without this drug, talazoparib. Dr. Gilligan: So they will get either-- what you described before is the standard of care—hormonal therapy, or that combined with this new drug. Dr. Pal: That's exactly right, Dr. Gilligan. Dr. Gilligan: I wanted to make that clear because this is a trial that has placebo, and sometimes research [participants] have concern about, "Do I want to be on a trial that has a placebo?" Do you want to say anything about that? Dr. Pal: It's very important to bear in mind that every patient that enrolls in this study is going to get the standard treatment in this setting. As I've mentioned before, enzalutamide represents one of those options. And, of course, in this trial above and beyond that, they have the possibility of getting talazoparib or a placebo. So certainly patients won't be receiving placebo alone in this trial. Dr. Gilligan: Do you want to say anything more about what's kind of interesting about this new approach to treating prostate cancer? Dr. Pal: What I think is quite inventive about this study is that talazoparib, the PARP inhibitor, is being combined with hormone therapy. And I think that's the real difference in what this protocol offers versus the treatment strategies that now represent a standard option for patients. Dr. Gilligan: Right. And my understanding is that the hope is that by using this combination, we'll be able to make treatment more effective. Dr. Pal: Absolutely. When we talk about PARP inhibitors and prostate cancer currently, we're typically restricting it to patients who have these so-called DNA damage repair mutations. And that's certainly a finite group of individuals. In this particular trial, we're actually going to look not just at those patients, but all patients within this disease state. So we go beyond the 25 to 30 percent of patients who are estimated to have alterations in DNA damage repair. Dr. Gilligan: Right. I think that's an important point: to get on this trial, patients don't have to have a particular genetic profile. So how will success be evaluated? How will we know if it's working? Dr. Pal: In this case, we're going to be looking at the delay in cancer growth as the primary outcome measure. We're certainly hoping that the combination of enzalutamide with talazoparib is going to slow growth relative to enzalutamide plus placebo. The innovative endpoint that's explored in this study is also diving deeper and looking at those patients who have these DNA damage repair mutations that's going to also reflect one of the primary outcome measures in this study. And that's something quite important to bear in mind. Dr. Gilligan: So we have some experience with PARP inhibitors. Can you say something about what we know about the side effects? Dr. Pal: Fatigue is a relatively common side effect. Decreases in blood counts is another potential side effect. And in particular in my clinical experience, I've seen drops in the white blood cell counts. That of course makes patients more susceptible to infection. Diarrhea may also be one of the consequences within this class of drugs. And certainly, I would refer patients to a more comprehensive discussion of these side effects with their clinicians before entering into the study. Dr. Gilligan: Is the trial still accruing patients? And do we know when we might expect results? Dr. Pal: I think that there are many trials within this particular space. This one is ambitious in that it hopes to accrue over a thousand patients. I don't have a good finger on the pulse of when results will report. But I'm sure that'll be the subject of future podcasts for us.  Dr. Gilligan: Well, thank you very much Dr. Pal. It's a very exciting study and exciting new area of research in prostate cancer. Dr. Pal: Definitely. Dr. Gilligan: We're going to move on now to the second study we want to talk about, which is the KEYNOTE-905 study. [Perioperative Pembrolizumab (MK-3475) Plus Cystectomy or Perioperative Pembrolizumab Plus Enfortumab Vedotin Plus Cystectomy Versus Cystectomy Alone in Cisplatin-ineligible Participants With Muscle-invasive Bladder Cancer (MK-3475-905/KEYNOTE-905/EV-303)] And Dr. Grivas is going to talk to us about that. Can you orient us, Dr. Grivas, to what this study is, for which group of patients, and what it's looking at? Dr. Grivas: This clinical trial is applicable to patients with localized, meaning not spread, bladder cancer. And when the bladder cancer has invaded the muscle layer of the bladder, we call this muscle invasive bladder cancer. And these patients usually go for cystectomy, the removal of the bladder. And ideally, they get chemotherapy before, but some patients may not be fit enough for chemotherapy. So those patients go straight to cystectomy, the removal of the bladder. So this clinical trial is trying to evaluate whether immunotherapy with this drug, called pembrolizumab, helps these patients before they get the cystectomy. Dr. Gilligan: Can you tell us a little bit more about pembrolizumab and what we know about it? Where it's used currently in bladder cancer? Dr. Grivas: Pembrolizumab has three different indications for patients with bladder cancer. The first one is in an earlier stage, what we call non-muscle invasive bladder cancer, which is a very superficial cancer, when the cancer is not invading through the muscle layer. And there's a specific indication for those patients who get therapy with BCG, which is a form of immunotherapy given inside the bladder. And if the cancer is not responding well to this BCG, usually, they go for removal of the bladder. But some of them may not be able to do that or do not want that. And pembrolizumab has a track record in those specific scenarios of BCG-unresponsive tumors as we call them for those patients who cannot get cystectomy or don't want to have it. The other two indications are for patients who have metastatic, [meaning bladder cancer that has spread to other organs.] And there are two specific indications of pembrolizumab immunotherapy in that particular setting. So this trial is trying to expand upon the role of pembrolizumab in bladder cancer. Dr. Gilligan: So it's been shown to be a benefit when the disease is more advanced and now we want to see if it's helpful earlier on in the period of time around surgery. Dr. Grivas: Right. And it's interesting in a particular setting we're looking at this trial, because we have indications literally before and after in an earlier states, the non-muscle invasive disease setting. And also as you mentioned, Dr. Gilligan, in the more advanced setting. So we're trying now to see whether this middle setting of muscle invasive bladder cancer, whether there's a role of pembrolizumab by itself before removing the bladder. Dr. Gilligan: Are patients who are eligible to get chemotherapy prior to cystectomy able to go on this trial or is it only for patients who are not [well enough] to get chemotherapy? Dr. Grivas: This is for patients who are not in good condition to undergo chemotherapy. So if someone is in good condition to undergo chemotherapy, then the trial does not apply to them. This is only in those who cannot safely receive chemotherapy before the cystectomy. Dr. Gilligan: Thank you for clarifying that. What data do we have that makes us think that it may be a good idea to give immunotherapy prior to cystectomy? Because this has been looked at a little bit already, and I think it's why this trial is being done. Can you say a little bit about that? Dr. Grivas: Sure. I would like to underline that as you alluded before, the standard of care therapy for patients who undergo cystectomy, the removal of the bladder, is to undergo chemotherapy with a drug called cisplatin before cystectomy. But as we discussed before, this is the standard of care with a high evidence. However, many patients, maybe 50, maybe 55 percent of patients may not have enough condition to undergo this chemotherapy safely. And that is the population we would try to capture. And to answer your question, there have been so far, four clinical trials looking at immunotherapy before cystectomy. And all of those four clinical trials look very promising in that regard. So based on this promising information, this new trial the KEYNOTE-905 is a phase III trial trying to confirm the promising data from the previous phase II trials and help us make a final decision whether this should be the standard of care or not in patients who cannot undergo safely chemotherapy in that setting. Dr. Gilligan: What are the known side effects and risks of immunotherapy? Dr. Grivas: Immunotherapy overall is much better tolerated than chemotherapy. However, it can still cause significant side effects, especially in a small proportion of patients. So the main thing we need to keep an eye on is if the immune system gets too overstimulated, it can cause what we call immunotherapy-related adverse events or side effects. And any organ of the body could in theory be attacked by an overstimulated, overactive, immune system. So they are different forms of “-itis.” For example, if you have inflammation in the lungs, it's pneumonitis. In the liver, hepatitis. So we have to be careful and educate our patients, educate our medical providers and the teams, follow the patients and then report any new symptoms for changes in order to be able to recognize early and manage properly these side effects. As I mentioned, it's not common to have a severe reaction, but it can happen. So education helps, and I recommend to the patients to discuss with a medical provider the potential of those immunotherapy-related adverse events that usually, if they occur, can be managed with proper treatment to try to suppress, “cool down,” the immune system. So education is important. Dr. Gilligan: So just to summarize then, this is a trial for patients who would normally be treated with surgery alone, and we're looking at whether adding immunotherapy before and after surgery can improve those outcomes. Dr. Grivas: That's exactly right. Especially for those patients who cannot safely undergo chemotherapy before the surgery. Dr. Gilligan: And how are we going to measure whether it's successful? Whether that immunotherapy has improved outcomes or not? Dr. Grivas: The two measures that we're are looking at in this particular trial are the following. Number one, we tried to see how many patients--what is the proportion of patients from everybody who gets in the trial—who has no residual cancer cells at the time of the removal of the bladder, at the cystectomy. When the pathologist looks at the cystectomy sample in the lab after the bladder is removed from the body, what is the proportion of patients with no cancer inside the bladder after the immunotherapy compared to no immunotherapy at all? So we're going to compare these. We call this “complete response,” meaning no cancer is found in the bladder after its been removed, after the immunotherapy. And we're going to compare this complete response in the two groups. The other metric we use is to see how many patients have no recurrence regardless, meaning the cancer came back after the treatment. After the cystectomy, how many of those patients either had the cancer come back later or died from another cause. So we use these metrics and we compare the two metrics in the two populations in the trial with and without immunotherapy before the surgery. Dr. Gilligan: And currently, the relapse rate's roughly 50 percent, so we're hoping for a lower number than that. Dr. Grivas: Correct. We try to look for a lower number, and we try to see to compare these two populations with and without immunotherapy and see if immunotherapy adds value in that particular setting. Dr. Gilligan: Is this trial still open and do you know when we might see results from it? Dr. Grivas: The trial is open. It started recently, so I will strongly encourage the patients to discuss with their providers and look at particular locations where this trial is open. So definitely, there is room to go. And I think the trial will take a few years to complete and then report the results. So definitely an ongoing trial options for the patients. Dr. Gilligan: Great. Well, thank you very much. So an exciting trial for patients with localized bladder cancer going through surgery to see if we can improve outcomes, increase the cure rate, by adding this interesting new immunotherapy. Thank you, Dr. Grivas. Dr. Grivas: Thank you so much. Dr. Gilligan: So now we're going to move on and talk about the COSMIC-313 trial with Dr. Zhang from the Duke Cancer Institute. [Study of Cabozantinib in Combination With Nivolumab and Ipilimumab in Patients With Previously Untreated Advanced or Metastatic Renal Cell Carcinoma (COSMIC-313)] Can you tell us who this trial is designed for, or which group of patients? Dr. Zhang: Absolutely. We know that for patients with kidney cancer with a clear cell component and intermediate or poor risk by IMDC criteria, that both immunotherapy combinations with ipilimumab and nivolumab as well as the targeted therapy blocking blood vessel formation, called cabozantinib, have both demonstrated significant benefit for these patients. And these are approved treatments. So this particular trial is attempting to combine these starting as a triplet of ipilimumab, nivolumab, cabozantinib for four cycles and then maintenance nivolumab with cabozantinib. And this triplet treatment is compared to a placebo-controlled regimen of the same immunotherapies without the targeted therapy. Dr. Gilligan: So if a patient weren't going to go on this trial, what's the current standard of care? Dr. Zhang: Both the immunotherapy combination as well as having the cabozantinib by itself, are our standard of care therapies for these patients in these categories. Dr. Gilligan: Is this restricted to any particular group of kidney cancer patients? Dr. Zhang: These patients must have at least one of the IMDC criterion. So these are markers of inflammation, like high neutrophil count, low hemoglobin, or high platelet levels, high calcium levels, as well as poor performance status in less than one year from diagnosis to needing these type of treatments. Patients have to have kidney cancer that spread to other sites of their body or locally advanced disease which is not surgically resectable. And as a note, other treatments that are approved in patients who have intermediate poor risk disease include combinations of immunotherapies with targeted therapies like pembrolizumab with axitinib or avelumab with axitinib. Dr. Gilligan: So then just to be clear, these are drugs that are already being used, have already been shown to work, and we're trying to see if we combine them do we get a better result than using them by themselves. Dr. Zhang: That's right. And I think that's a main point. If two agents work on their own, can they be combined to work better? It is important to note that we must follow these patients for their side effects to make sure that the benefit of the triplet therapy would be worth the potential added toxicity of this combination. Dr. Gilligan: So as you mentioned, there's already a standard treatment that includes targeted therapies, immunotherapies, axitinib and pembrolizumab. What do you think is the interesting or different about the approach in this study? Dr. Zhang: The main difference of this triplet combination is the addition of ipilimumab which is a CTLA 4 inhibitor. This is even a bit of a stronger immunotherapy, which targets the dendritic cell interaction with cells to activate the immune cells even more. And so we know that ipilimumab in kidney cancer does drive increase the ability for us to achieve a complete response, meaning that this combination is a really active immunotherapy combination for metastatic kidney cancer. So if we can add the ipilimumab effect with a very strong targeted effect of the cabozantinib the thought is that this triplet might be even more effective than the current standard of care, pembrolizumab-axitinib or avelumab-axitinib combinations. Dr. Gilligan: Thank you for clarifying that. Just to make sure our listeners are clear on this. They're two doublets that are already approved—two kinds of immunotherapy or immunotherapy combined with targeted therapy. This will be the first triplet, if I understand correctly, that if this is shown to be more effective, it would be the first triplet therapy where we're using three different agents, our strongest immunotherapy combined with targeted therapy. Is that a fair summary? Dr. Zhang: Absolutely. I think that's a great summary. Dr. Gilligan: So how will success be evaluated? What are the endpoints for this? Dr. Zhang: Success for this particular study will be evaluated by improving time until tumor growth and the safety of the triplet combination so the primary outcome of this particular study is improving progression free survival. But one of the key secondary endpoints, of course, is to make sure that the benefit of this triplet is worth the potential combined side effects. And then also to follow patients and see if it also improves survival to make patients live longer. Dr. Gilligan: Do we have any sense of how long it'll be before we see outcomes from this? Or results? Dr. Zhang: This is an ongoing international trial enrolling in the US but also spanning Europe, Asia, South America, Australia, and New Zealand sites. It will enroll up to 676 patients, and it's open currently. And patients should discuss it with their oncologist and see if it's open in a site close to them. Dr. Gilligan: Dr. Grivas earlier told us about some of the side effects or risks with immunotherapy. This is combining immunotherapy with targeted therapy. Can you say a little bit about what we're gonna be watching for in terms of side effects or what we might expect? Dr. Zhang: Sure. I think all of the immunotherapy side effects that Dr. Grivas told us about pertain to this study as well. The rashes, the diarrhea, inflammation of the lungs or liver, and affected endocrine dysfunction. But the targeted therapies can also have high blood pressure, rashes on the hand and feet, so called hand foot syndrome, also diarrhea, and elevation of liver enzymes, as well as the loss of protein in the urine. I think the one overlapping toxicity of cabozantinib with a combination of ipilimumab and nivolumab, the immunotherapy combination, is the diarrhea. So patients who start on this trial should be careful to report any diarrhea early on so that their oncologist and their investigators on the study can get an early handle and manage their diarrhea well. Dr. Gilligan: Thank you. That's very helpful. One last question, I want to get back to that issue of eligibility. Sometimes when cancer patients want to go on a trial and they find that they are told they're not eligible to go on, this trial looking at intermediate risk patients specifically so a good risk patient might want to go on it and couldn't. Can you say a little bit about how those decisions are made and what the rationale for selecting groups of patients for trials is? Dr. Zhang: Sure. We know that the IMDC criteria were really made in the setting of targeted therapies, and they were a set of prognostic markers and markers of inflammation, for example, and of time from initial diagnosis to treatment. But now they've been used often as stratification markers in our treatment trials and as selection now for eligibility. In particular for this patient population, ipilimumab, nivolumab seem to have more benefit in this intermediate and poor risk population. And so that's why, for this particular study, they're selecting specifically those patients with intermediate poor-risk disease. Dr. Gilligan: So we want to focus on the patients who are most likely to benefit, it sounds like you're saying. Dr. Zhang: That's right. So the favorable risk patient population do have a better prognosis in general, but those patients may not have as much benefit from the immunotherapy doublet. Dr. Gilligan: All right. Thank you. Well, that brings us to the end of this podcast. Thanks for listening. There are many different clinical trials currently enrolling people with genitourinary cancers. If you're wondering whether participating in a clinical trial might be right for you, please talk to your health care team. This is Timothy Gilligan. Thank you very much. ASCO: Thank you, Drs. Gilligan, Pal, Grivas, and Zhang. Visit www.cancer.net/clinicaltrials to learn more about participating in clinical trials. All treatments have side effects—please talk to your health care team about possible side effects to watch out for. And if this podcast was useful, please take a minute to subscribe, rate, and review the show on Apple Podcasts or Google Play. This Cancer.Net podcast is part of the ASCO Podcast Network. This collection of 9 programs offers insight into the world of cancer care, covering a range of educational, inspirational, and scientific content. You can find all 9 shows, including this one, at podcast.asco.org. Cancer.Net is supported by Conquer Cancer, the ASCO Foundation, which funds breakthrough research for every type of cancer, helping patients everywhere. To help fund Cancer.Net and programs like it, donate at conquer.org/donate.

Proceedings from a CME symposium held at the 2020 Genitourinary Cancers Symposium. Featuring perspectives from Dr Toni K Choueiri, Dr Thomas E Hutson, Dr David F McDermott and Prof Thomas Powles. Introduction Program Overview: Dr Neil Love (00:00) Optimizing Front-Line Decision-Making for Advanced Renal Cell Carcinoma (RCC) Roundtable Discussion (0:34) Faculty Presentation — Prof Powles (23:01) Selection and Sequencing of Therapy for Patients with Relapsed/Refractory RCC Roundtable Discussion (37:02) Faculty Presentation — Dr Choueiri (46:49) Novel Strategies Under Investigation in RCC Roundtable Discussion (1:00:09) Faculty Presentation — Dr Hutson (1:13:29) Identification and Management of Adverse Events Associated with Immune Checkpoint Inhibitor and TKI Therapy Roundtable Discussion (1:25:45) Faculty Presentation — Dr McDermott (1:34:03) CME information and select publications

Proceedings from a CME symposium held at the 2020 Genitourinary Cancers Symposium. Featuring perspectives from Drs Emmanuel S Antonarakis, Andrew J Armstrong, Karim Fizazi and Matthew R Smith. Introduction Program Overview: Dr Neil Love (00:00) Integration of Antiandrogens into the Management of Nonmetastatic Castration-Resistant Prostate Cancer (CRPC) Roundtable Discussion (0:44) Faculty Presentation — Dr Fizazi (16:53) Current Treatment of Metastatic Hormone-Sensitive PC Roundtable Discussion (29:35) Faculty Presentation — Dr Smith (43:16) Optimal Management of Metastatic CRPC (mCRPC) Roundtable Discussion (53:24) Faculty Presentation — Dr Armstrong (1:03:03) PARP Inhibition as a Therapeutic Strategy in mPC Roundtable Discussion (1:17:24) Faculty Presentation — Dr Antonarakis (1:26:14) CME information and select publications

Proceedings from a CME symposium held at the 2020 Genitourinary Cancers Symposium. Featuring perspectives from Drs Peter H O’Donnell, Daniel P Petrylak, Elizabeth R Plimack, Jonathan E Rosenberg and Guru Sonpavde. Introduction Program Overview: Dr Neil Love (00:00) Immune Checkpoint Inhibitors for Patients with Nonmetastatic Urothelial Bladder Cancer (UBC) Roundtable Discussion (1:05) Faculty Presentation — Dr Plimack (13:05) Role of Anti-PD-1/PD-L1 Antibodies in the Up-Front Management of Advanced UBC Roundtable Discussion (25:17) Faculty Presentation — Dr Rosenberg (39:50) Application of Anti-PD-1/PD-L1 Antibodies for Progressive Metastatic Disease; Ongoing Investigation of Immune Checkpoint Inhibitors in Advanced UBC Roundtable Discussion (54:11) Faculty Presentation — Dr O’Donnell (1:02:25) Approved and Investigational Antibody-Drug Conjugates for Advanced UBC Roundtable Discussion (1:13:41) Faculty Presentation — Dr Petrylak (1:23:53) FGFR-Targeted Strategies in Advanced UBC Roundtable Discussion (1:35:35) Faculty Presentation — Dr Sonpavde (1:45:18) CME information and select publications

This week, we'll be reviewing data from three influential abstracts presented at the recent 2020 Genitourinary Cancers Symposium in San Francisco—one on a novel, first-in-class, small molecule, hypoxia-inducible factor 2 alpha inhibitor for heavily pretreated patients with metastatic clear cell renal cell carcinoma; the second, on whether pembrolizumab in combination with the antibody-drug conjugate enfortumab vedotin may be an alternative option for platinum-ineligible patients with locally advanced or metastatic urothelial carcinoma; and the third, on treatment with pembrolizumab plus enzalutamide after disease progression on enzalutamide in patients with castration-resistant prostate cancer.

ASCO: 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 world’s leading professional organization for doctors who care for people with cancer. The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Cancer research discussed in this podcast is ongoing, so clinical trials described here may no longer be enrolling patients, and final results are not yet available.   Before any new cancer treatment can be approved for general use, it must be studied in a clinical trial in order to prove it is safe and effective. In today’s podcast, members of the Cancer.Net Editorial Board discuss 3 clinical trials that are exploring new treatment options across prostate, bladder, and kidney cancer. This podcast will be led by Dr. Sumanta (Monty) Pal, Dr. Neeraj Agarwal, Dr. Petros Grivas, and Dr. Tian Zhang. Dr. Pal is co-director of City of Hope's Kidney Cancer Program and is the head of the kidney and bladder cancer disease team at the institution. He has served in a consulting or advisory role for Novartis, Genentech Roche, and Bristol-Myers Squibb. Dr. Agarwal directs the Genitourinary Oncology Program at the Huntsman Cancer Institute at the University of Utah. He has served in a consulting or advisory role for Novartis and Bristol-Myers Squibb. Dr. Grivas is the clinical director of the Genitourinary Cancers Program at University of Washington Medicine. He is also an associate member of the clinical research division at the Fred Hutchinson Cancer Research Center. He has served in a consulting or advisory role for Genentech Roche and Bristol-Myers Squibb. Dr. Zhang is an assistant professor of medicine at Duke University School of Medicine and is a medical oncologist at Duke Cancer Institute. She has served in a consulting or advisory role for Genentech Roche and Bristol-Myers Squibb. View full disclosures for Dr. Pal, Dr. Agarwal, Dr. Grivas, and Dr. Zhang at Cancer.Net. Dr. Pal: Hi, I'm Monty Pal from City of Hope. I'm the Associate Editor for Genitourinary Cancers for Cancer.Net, ASCO's patient education website.  I'm really excited to be here with my colleagues: Dr. Petros Grivas, Dr. Neeraj Agarwal, and Dr. Tian Zhang. We're really excited about this effort. We're hoping it brings some salient details about clinical trials straight to you, our most important audience. Keep in mind that clinical trials are the main way that doctors are able to find better treatments for diseases like cancer. And before any new drug can be approved by the FDA, it must be studied in the context of a clinical trial. Patient participation is vital for clinical trials. By participating in a clinical trial, you can directly help researchers develop better treatments, reduce side effects, or even reduce the risk of cancer altogether. While you may receive new treatments within a clinical trial, the primary purpose of these studies is to move the field of cancer research forward. Keeping participants safe is probably the most important concern in clinical trials, and there may be some risks involved. Because of that, your healthcare team is going to discuss with you in detail these risks before you join on to a clinical study. Now, at this point in time, we're going to discuss 3 studies that are being done in the area of kidney, bladder, and prostate cancer. These studies were chosen by members of the Cancer.Net Editorial Board Genitourinary Cancers panel from the Trials in Progress abstracts that are going to be presented at ASCO's 2020 Genitourinary Cancers Symposium. I'd like to note that none of us have any direct involvement with any of these trials. Each one of us will post our disclosures on the ASCO website if you'd like to see them. We'll certainly have them posted on the Cancer.Net website. I'd like to begin by introducing my very esteemed panel.  First, is Dr. Tian Zhang, who's an expert in kidney, bladder, and prostate cancer from Duke Cancer Research Institute. We have Dr. Neeraj Agarwal, who heads up the Genitourinary Cancers Program at the Huntsman Cancer Institute at the University of Utah. And last, but not least, we have Dr. Petros Grivas from the Fred Hutchinson Cancer Research Institute in Seattle, Washington, an expert in many disease types, including bladder cancer. I'd like to bring on my first guest, Dr. Neeraj Agarwal, to discuss the VISION study. [VISION: An International, Prospective, Open Label, Multicenter, Randomized Phase 3 Study of 177Lu-PSMA-617 in the Treatment of Patients With Progressive PSMA-positive Metastatic Castration-resistant Prostate Cancer (mCRPC)] Neeraj, this is a study in prostate cancer. What particular patient population within prostate cancer are we focused on here with this study? Dr. Agarwal: So this is a patient population with advanced prostate cancer where prostate cancer has gone beyond prostate to different parts of the body. In technical terms, we call it metastatic prostate cancer. The usual treatment paradigm for these patients is to be treated with hormonal blockade therapies, which can include injections and oral pills, which have different mechanisms to prevent stimulation of testosterone to the prostate cancer cells. However, every patient with metastatic prostate cancer eventually are failed by these treatment options, and the next commonly used treatment option is chemotherapy, which usually controls the disease for a period of many months, up to one year. And after, patient's disease progresses on these 2 different therapeutic options, which include hormonal therapies and chemotherapies. And this is the patient population in which this novel type of radiation therapy or radiation particle treatment is being tested. Dr. Pal: Tell us about what question this study aims to answer. Dr. Agarwal: This study is testing a novel medication, which is a type of a radiation particle, which is supposed to target prostate cancer cells. So whether using this kind of radiation particle in patients with advanced prostate cancer, who have been failed by previous chemotherapy and novel, hormonal therapies. The study is asking whether using this radiation particle as a treatment may improve overall survival. Dr. Pal: Now, this compound is called 177Lutetium-PSMA-617. It's a long name. Tell us about what it actually does. What's the rationale for using this particular drug? Dr. Agarwal: I would like to divide this long name into 2 parts to make it simple. So 1 is the lutetium particle, which is the radiation particle, is a type of radiation known as beta radiation. So lutetium is tagged onto a PSMA-identifying agent known as PSMA-617. So if we just inject PSMA-617, it will go and seek prostate cancer cells, which are expressing PSMA on their surface. If you tag this radiation particle lutetium to the PSMA-617, what essentially happens is that PSMA-617 takes this radiation particle directly to the prostate cancer cells. Dr. Pal: Now, what is this study attempting to demonstrate? Dr. Agarwal: This study is specifically looking at 1 question, which is whether using this radiation particle can improve survival in patients with metastatic prostate cancer who have had disease progression on novel hormonal therapies and chemotherapies. Dr. Pal: And again, it's hard to be comprehensive in a podcast like this, so of course, we refer patients to their physicians for a discussion around safety of these drugs. But could you tell us about any known risks that patients should be aware of in the context of this agent? Dr. Agarwal: Yes. So as you can imagine, this PSMA-617, which is loaded with this radiation particle, is looking for those cells in our body which are expressing PSMA. So of course, the PSMA is expressed highly by prostate cancer cells. But there are also normal cells which express PSMA to a lesser degree. And those cells may also have the potential to be targeted by this radiation particle. So technically, their other cells which may express PSMA, or which are in the vicinity of these cancer cells in the bone, such as bone marrow, these can be targeted to a much lesser degree because of the specificity of this compound. We can see some off-target toxicities, as we call them, but given the highly targeted nature of this compound, those toxicities are usually very well tolerated, except in rare circumstances. Dr. Pal: Excellent, Neeraj. Now, for a little additional commentary on the VISION trial, I'm going to throw it to Dr. Tian Zhang, again, an expert at the Duke Cancer Research Institute Tian, you've had some experience enrolling patients on VISION, correct? Dr. Zhang: That's right, Monty. Thanks so much for having me on. And VISION has actually completed accrual. It was open for a few months here at Duke. We were able to enroll about 10 patients and we're really looking forward to seeing the results of VISION over the next year or 2. And I think it'll be quite applicable to clinical practice. Now, I want to mention that although VISION has completed enrollment, there are other clinical trials that are using PSMA-targeted Lutetium-617 agent as a possibility for other patients to enroll on to other trials in clinical development as we speak, and so there will be other opportunities to receive this agent. Dr. Pal: We're going to shift gears now from prostate cancer and move on to the topic of bladder cancer. And again, I'm thrilled to have Dr. Petros Grivas from the Fred Hutch Cancer Research Institute to discuss a very important trial called INTACT. [Phase III Randomized Trial of Concurrent Chemoradiotherapy With or Without Atezolizumab in Localized Muscle Invasive Bladder Cancer (Study SWOG/NRG 1806)] Petros, the study INTACT really addresses a very important question. Can you tell us a little bit more about it? Dr. Grivas: Thank you, Monty. I think this trial is very important for a number of reasons. Number 1 is trying to address an important clinical question, which is the following: Patients who we consider candidates for bladder-preservation approach, meaning, we try to keep the bladder in place and still kill the cancer, which is not a good option for everybody with bladder cancer. But the proportion of patients after discussions of pros and cons with their providers could be offered this bladder-preservation approach, which is consisted of an optimal resection of the tumor through a procedure called transrectal bladder tumor resection, which means try to remove the bladder tumor through a procedure that is similar to cystoscopy, when you look inside the bladder. And after this tumor is removed, then there is a combination of chemotherapy and radiation, at the same time—we call this concurrent or concomitant—at the same time, chemotherapy and radiation. This approach, which involves the collaboration between the urologic oncologist, medical oncologist, and radiation oncologist, is the standard of care, the standard approach, how we try to preserve the bladder and still kill the cancer in those patients who are considered good candidates for this approach, which, as I've mentioned, is not for everybody. The clinical question is can we improve upon this backbone of chemotherapy and radiation, which is current standard of care, by using a third modality, a third type of treatment, which is immunotherapy? And immunotherapy is known to improve how people live in patients who have metastatic bladder cancer. For example, there's this particular drug called atezolizumab, which is already having FDA approval for patients with metastatic bladder cancer. The question is can we add this drug, the immunotherapy drug, that is activating the immune system, into the backbone of chemotherapy and radiation and use all three approaches, chemotherapy, radiation and immunotherapy together? And if that's the case, is that triplet combination better or not to the current standard of care, which is chemotherapy and radiation? So the INTACT trial is chemotherapy, radiation, plus immunotherapy with this drug called atezolizumab, together, all 3 of them compared to chemotherapy and radiation alone, in order to see whether we can improve upon the results we're getting with chemotherapy and radiation. The primary end point of this particular trial is what we call bladder intact disease-free survival, which means the proportion of patients who have no cancer coming back after treatment. They have what we call a complete response, remission of the cancer, and they still have the bladder intact, in place. And this is what we call a metric of success. This is a huge effort among different investigators across the country. These studies open in multiple cancer centers and sites across the nation. And I think it's a very good example of what can happen in terms of a clinical trial design that is applicable to many patients when different collaborations take place and when people put their minds together. So we're really very enthusiastic about this study, and we'll try to support the accrual and offer this option to the patients who are considered to be good candidates for this attempt for bladder preservation. Dr. Pal: Petros, thanks. That was a great overview of the study. You've really highlighted the rationale and some detail and the metrics for success of this trial. Now, on the subject of this approach, are there any risks that you think patients should be particularly aware of? And again, we leave it to the discretion of treating physicians to have that very thorough discussion of risks and benefits. But off the top of your head what would you counsel patients, in general? Dr. Grivas: I think, Monty, that's a great question, in general, because when a patient is undergoing evaluation for a clinical trial, it's important for them to understand thoroughly the pros and cons of this particular therapy and other procedures and what those mean for the patient's logistical, day-to-day schedules, as well as potential short-term and long-term side effects. In that particular study, I think the important take-home message is we're trying to evaluate the additional role of immunotherapy to the backbone of chemotherapy and radiation. So potential side effects of immunotherapy are something that are very important to be discussed with the patient. Some of the patients may develop fatigue or some degree of occurrence of what we call immune-related adverse events, which means the immune system gets activated, stimulated against the cancer but can, potentially, in a small proportion of patients generate a significant reaction, an immune system activated related reaction against different parts of the body or some parts of the body. So I think it's very important for the patients to discuss carefully with the providers what are those uncommon, but sometimes significant, immune-related adverse events, and have a very good understanding of what symptoms [to] look for in order to be able to communicate or recognize early those potential side effects and have a proper management plan. Because most of those side effects could be managed properly, and with good success, especially if they're caught up early. So I think it's important to have these thorough discussions with the provider. And of course, the side effects of chemotherapy and radiation should be discussed in thorough detail. This is the standard of care, but still is important to delineate what potential side effects can happen. At the end of the day, it's in the balanced discussion about pros and cons. This is a very exciting trial, but I think good education for the patient and their families and their caregivers are very important and critical for the successful detection or diagnosis of any potential side effects. Overall, I think this is a very relevant discussion to have with the provider and a very exciting trial to be involved in. Dr. Pal: Excellent, Petros. Well, great discussion of some of the risks associated with this approach. Neeraj, any thoughts on INTACT? Why should patients be excited about this particular trial? Dr. Agarwal:  I was recently talking to one of my patients about this upcoming trial, who is preparing to go on radiation therapy plus chemotherapy as a treatment option for his muscle-invasive bladder cancer, and cystectomy is not an option. And the way I explained this to the patient is 95% of the work he will have to do will be done by the time he's getting radiation therapy and chemotherapy. And after that, 5% of the work, as far as patient's effort, side effects, toxicities, impact, and quality of life, all are concerns, 95% of that, in my view, is coming from radiation therapy and chemotherapy. And after that, little work from that perspective by the patient has to be done by atezolizumab, as far as getting treatment with atezolizumab is concerned. So as Petros said, this is a highly well-tolerated treatment, which is immunotherapy. And if you look at the potential of this drug to control the recurrence of the disease and allow our patients to maintain their bladder—it’s tremendous. So I think the expected returns are very high, and how much effort patients will have to put on the trials are not as high as you would expect if you are thinking about a trial. Dr. Pal: That was an excellent discussion of toxicities associated with this particular regimen, Neeraj. Petros, before we move on any closing thoughts? Dr. Grivas: No, I agree completely with Neeraj. I think these are important points. I just wanted to add a couple of key take-home message for the patients. Number 1, this trial is available for patients who either are or are not candidates for radical cystectomy, which is the removal of the bladder and again, it has to be a discussion with the providers whether they're good candidates for the attempt for bladder preservation. Half of the patients get the standard of care, which is chemotherapy and radiation at the same time, and the other half get chemotherapy and radiation, plus this immunotherapy called atezolizumab. And again, I think the last point to make is that chemotherapy and radiation have to happen at the cancer center, and some of the patients live far away, so I think it's important to discuss with the patients the pros and cons of the trial because it might entail some back and forth transportation for them if they have to get the radiation and the chemotherapy in the cancer center that is offering the trial. But overall, as Neeraj pointed out, we are very enthusiastic, and I'm personally enthusiastic about the study. Dr. Pal: That's great Petros, appreciate that. Now, in the final portion of our program, we're going to shift gears and talk about the type of cancer that I actually focus on personally in the clinic, and that is kidney cancer. And we have our resident expert in kidney cancer on the Cancer.Net panel, Dr. Tian Zhang from Duke here to discuss the PROSPER study, a very important national effort. [A Phase 3 Randomized Study Comparing Perioperative Nivolumab vs. Observation in Patients With Renal Cell Carcinoma Undergoing Nephrectomy (PROSPER RCC)] Tian, can you tell us about PROSPER? Dr. Zhang: PROSPER is a phase III trial that's open currently for patients who have locally advanced kidney cancer, and we know that in this population of patients who have locally advanced kidney cancer who undergo their surgery, there's still a high rate of recurrence up to about 50% with many dying, unfortunately, from disease recurrence. And so the question that PROSPER aims to answer is can we prevent disease from recurring, and thereby, can we allow patients to live longer from giving up-front systemic therapy in addition to their surgery? And so in kidney cancer, we know that patients will benefit from immune checkpoint inhibitors, and the big question of the study is that with the primary kidney cancer in place, what is the effect of this immunotherapy called nivolumab before and after surgery compared to surgery alone, and how should we use these immunotherapy agents in the perioperative setting to improve overall survival? Dr. Pal: That's very interesting. Of course, in kidney cancer, just as we discussed with prostate cancer, you've got patients who have the disease confined to the kidney. You have patients where the disease has spread. What particular patient population does this study focus on? Dr. Zhang: This study is enrolling patients with locally advanced disease, so either clinical stage II or higher. So that's patients who have primary tumors of greater than seven centimeters, or if they have positive lymph nodes on their scan, so clinical detection of lymph node-positive cancer. Or the study, actually, also allows cancer that has spread to no more than three, so one, two, or three, other sites, which can also be definitively treated at the time of the primary surgery. Patients who have disease spread to the lung, adrenal gland, lymph nodes, pancreas, or soft tissue are allowed. Patients who have spread to the liver or bone are not allowed. And the study is currently ongoing, Monty. It is randomizing up to 805 patients total. As of late January 2020, they're currently at about 390 patients already enrolled. So there's plenty more, about 400 more patients to go on the study. And it is an open and enrolling study. Dr. Pal: That's really interesting. Now, Petros gave us some insights as to the rationale for using immunotherapy in cancer. Is it the same rationale for using this treatment strategy in kidney cancer? Dr. Zhang: Sure. So our standard of care in this setting, as you know, for locally advanced disease is truly just nephrectomy alone to remove the kidney, usually without treatment afterward. And there are multiple adjuvant studies using immunotherapies in this post-operative setting, however, those are all pending. And we're hoping that immunotherapy used earlier in the disease course will allow us to see a benefit overall. Now, nivolumab, the immunotherapy that's studied in the PROSPER trial, is approved for metastatic kidney cancer. And therefore, we know nivolumab is effective at extending overall survival for these patients. And so the question is if we can use this active immunotherapy agent earlier in the disease course if we can to try to prevent disease recurrence. Dr. Pal: That makes a lot of sense. Now, what is this particular study attempting to demonstrate? What are we trying to prove here with this trial? Dr. Zhang: Right. So the primary outcome of PROSPER is the time to disease recurrence or spread to other sites, what we call recurrence free-survival. There are secondary outcomes. So trying to get patients to live longer, overall survival, toxicity of giving nivolumab up front for these patients. As well as, specifically in patients who have clear cell kidney cancer, the time to disease recurrence for those patients, as well. So there are patients who are on the control cohort of surgery alone, and we'll be able to study that tissue in conjunction and compare those with patients who have received immunotherapy or nivolumab prior to their surgeries. So they have a number of biomarkers planned for the tissue that's being collected from the study. Dr. Pal: Very interesting. Well, I can't wait to see the results, ultimately, of this trial. But in the meantime, Petros had outline some of the risks associated with immunotherapy in the context of the study he discussed. Anything to add to that, in terms of the risks that might be entailed in this trial? Dr. Zhang: Right. So it is certainly a randomized trial, as Petros mentioned, so there are patients who are randomized to surgery alone versus patients who are randomized to the immunotherapy up front. So one dose of nivolumab followed by surgery and then maintenance treatment with nivolumab. And I fully agreed with the toxicity profile that Petros outlined very nicely. And when we get patients started on these immunotherapies treatments in clinic, I often talk about, we're activating your immune system, and therefore, toxicities can occur where the immune system is very active. So on the skin it can cause a rash, in the GI tract it can cause diarrhea or colitis, in a very small proportion of patients it can cause inflammation in the lungs or liver, and then, finally, it can affect their endocrine organs: the pituitary, thyroid, adrenal glands, and pancreas. And one more note about treatment with these immune checkpoint inhibitors of nivolumab, and other agents like nivolumab, is that these are really not for patients who have active autoimmune disease. We think that those patients who have active autoimmune disease requiring prednisone or other disease-modifying agents, those patients are probably going to have worsening of their baseline autoimmune disorder. So patients who do have that need to have a very close discussion with their providers before going on any of these trials. Dr. Pal: Well, that's an excellent overview of toxicity, and again, just as I mentioned earlier, I certainly leave it in the hands of the patient and their respective clinicians to go through a very thorough discussion of toxicity, but I think that was a fantastic primer on it, Tian. Thank you for that. Before we close, I wanted to go to Petros for any additional comments on this concept of the PROSPER study. Petros, any additional thoughts? Dr. Grivas: I think that Tian did a wonderful job summarizing all the key points. I think one of the key characteristics of this trial is, again, their rationale. The reasoning behind it, which as Tian mentioned, is we have the immunotherapy up front in the beginning of the treatment while the tumor is still present and the proteins, the antigens of the tumor, are still present, and that might be relevant in the recognition of those elements by the immune system when you give the immunotherapy. And then you have surgery, and then you have continuation of postoperative treatment, as Tian mentioned, and maybe that combination approach may be relevant. We have to see, of course, but I think it's a very, very compelling design that makes sense, at least scientifically speaking. The other point, I think, is as [inaudible] already mentioned, this very [inaudible] teamwork, team effort from multiple investigators across the country. And that speaks volumes of the very nice design, as well as the collaborative in spirit, which I think is important for that patient to know, that people do work together to come up with these clinical trials. We all hope that this trial will keep accruing well and will end up with accrual target in order to answer this important question which is, as Tian mentioned, whether immunotherapy before and after surgery prolongs life and improves the times of cancer remission, which is important and clinically relevant question. And of course, it's a key point to have discussions about sometimes uncommon but significant immune-related reaction and go through the different nuances carefully with the providers when a patient's considering clinical trial. But clinical trials, as you mentioned Monty, is the way to develop new therapies and are very important part of a discussion in the routine patient care. Dr. Pal: Excellent, Petros. Well, on behalf of Dr. Petros Grivas, Dr. Neeraj Agarwal, and Dr. Tian Zhang, I really want to thank you for joining our very first podcast from Cancer.Net. There's so many different clinical trials out there enrolling patients with genitourinary cancers, and we've only had time here to discuss 3 of them. If you have interest in participating in clinical trials, please do get in touch with your healthcare team. And of course, Cancer.Net serves as an excellent resource to communicate with experts in the field and learn more about respective genitourinary types of cancer. Thank you again for joining. ASCO: Thank you, Drs. Pal, Agarwal, Grivas, and Zhang. Visit www.cancer.net/clinicaltrials to learn more about participating in clinical trials. All treatments have side effects—please talk to your health care team about possible side effects to watch out for. And if this podcast was useful, please take a minute to subscribe, rate, and review the show on Apple Podcasts or Google Play. This Cancer.Net podcast is part of the ASCO Podcast Network. This collection of 9 programs offers insight into the world of cancer care, covering a range of educational, inspirational, and scientific content. You can find all 9 shows, including this one, at podcast.asco.org.  Cancer.Net is supported by Conquer Cancer, the ASCO Foundation, which funds breakthrough research for every type of cancer, helping patients everywhere. To help fund Cancer.Net and programs like it, donate at conquer.org/donate.

Consensus or Controversy? Clinical Investigators Provide Perspectives on the Current and Future Management of Prostate Cancer. A special audio supplement to a CME symposium held during the 2019 Genitourinary Cancers Symposium featuring expert comments on the application of emerging research to patient care. Interview with Emmanuel S Antonarakis, MD conducted by Neil Love, MD. Produced by Research To Practice.

Consensus or Controversy? Clinical Investigators Provide Perspectives on the Current and Future Management of Prostate Cancer. A special audio supplement to a CME symposium held during the 2019 Genitourinary Cancers Symposium featuring expert comments on the application of emerging research to patient care. Interview with Matthew R Smith, MD, PhD conducted by Neil Love, MD. Produced by Research To Practice.

Consensus or Controversy? Clinical Investigators Provide Perspectives on the Current and Future Management of Prostate Cancer. Proceedings from a CME symposium held at the 2019 Genitourinary Cancers Symposium. Featuring perspectives from Drs Emmanuel S Antonarakis, A Oliver Sartor, Howard I Scher, Matthew R Smith and Cora N Sternberg. Moderated by Neil Love, MD. Produced by Research To Practice.

Faculty presentations from a CME symposium held at the 2019 Genitourinary Cancers Symposium. Featuring perspectives from Drs Emmanuel S Antonarakis, A Oliver Sartor, Howard I Scher, Matthew R Smith and Cora N Sternberg: Incorporation of Androgen Receptor Antagonists into the Management of M0 Prostate Cancer (PC) — Dr Smith (00:00) Management of Metastatic Hormone-Sensitive PC — Dr Sternberg (05:12) Current and Future Management of Metastatic Castration-Resistant PC — Dr Scher (16:06) Biologic Rationale for and Ongoing Evaluation of PARP Inhibitors in the Management of Metastatic PC — Dr Antonarakis (26:04) Bone-Targeted Therapies and Other Emerging Radiopharmaceuticals — Dr Sartor (37:06) Select publications  

Go online to PeerView.com/FEJ860 to view the entire program with slides. In this activity, based on a recent live symposium held at the 2019 Genitourinary Cancers Symposium in San Francisco, experts in renal cell carcinoma (RCC) dip into their patient “CaseBook” to offer insights from their own practice on how best to bridge the divide between clinical research and daily care in the management of RCC. Pairing analysis of the latest evidence with application of key clinical concepts to decision-making in a complex therapeutic landscape, the expert panel explores how best to leverage the potency of newer agents across different RCC settings. Upon completion of this activity, participants should be better able to: Assess the latest evidence with and clinical implications of novel approaches, including new targeted agents, immune checkpoint inhibitors, and combination therapies in advanced renal cell carcinoma (RCC), Apply recently validated immunotherapy and targeted therapy options effectively for patients with advanced RCC that reflect optimal patient-centric selection and sequencing through multiple lines of therapy, Employ effective strategies to prevent and/or manage treatment-related complications with multi-targeted TKIs and immune checkpoint inhibitor therapy in patients with RCC, Recommend ongoing clinical trials assessing the latest therapies and/or combination approaches for advanced RCC patients in different disease settings.

Go online to PeerView.com/FEJ860 to view the entire program with slides. In this activity, based on a recent live symposium held at the 2019 Genitourinary Cancers Symposium in San Francisco, experts in renal cell carcinoma (RCC) dip into their patient “CaseBook” to offer insights from their own practice on how best to bridge the divide between clinical research and daily care in the management of RCC. Pairing analysis of the latest evidence with application of key clinical concepts to decision-making in a complex therapeutic landscape, the expert panel explores how best to leverage the potency of newer agents across different RCC settings. Upon completion of this activity, participants should be better able to: Assess the latest evidence with and clinical implications of novel approaches, including new targeted agents, immune checkpoint inhibitors, and combination therapies in advanced renal cell carcinoma (RCC), Apply recently validated immunotherapy and targeted therapy options effectively for patients with advanced RCC that reflect optimal patient-centric selection and sequencing through multiple lines of therapy, Employ effective strategies to prevent and/or manage treatment-related complications with multi-targeted TKIs and immune checkpoint inhibitor therapy in patients with RCC, Recommend ongoing clinical trials assessing the latest therapies and/or combination approaches for advanced RCC patients in different disease settings.

Go online to PeerView.com/FEJ860 to view the entire program with slides. In this activity, based on a recent live symposium held at the 2019 Genitourinary Cancers Symposium in San Francisco, experts in renal cell carcinoma (RCC) dip into their patient “CaseBook” to offer insights from their own practice on how best to bridge the divide between clinical research and daily care in the management of RCC. Pairing analysis of the latest evidence with application of key clinical concepts to decision-making in a complex therapeutic landscape, the expert panel explores how best to leverage the potency of newer agents across different RCC settings. Upon completion of this activity, participants should be better able to: Assess the latest evidence with and clinical implications of novel approaches, including new targeted agents, immune checkpoint inhibitors, and combination therapies in advanced renal cell carcinoma (RCC), Apply recently validated immunotherapy and targeted therapy options effectively for patients with advanced RCC that reflect optimal patient-centric selection and sequencing through multiple lines of therapy, Employ effective strategies to prevent and/or manage treatment-related complications with multi-targeted TKIs and immune checkpoint inhibitor therapy in patients with RCC, Recommend ongoing clinical trials assessing the latest therapies and/or combination approaches for advanced RCC patients in different disease settings.

Go online to PeerView.com/FEJ860 to view the entire program with slides. In this activity, based on a recent live symposium held at the 2019 Genitourinary Cancers Symposium in San Francisco, experts in renal cell carcinoma (RCC) dip into their patient “CaseBook” to offer insights from their own practice on how best to bridge the divide between clinical research and daily care in the management of RCC. Pairing analysis of the latest evidence with application of key clinical concepts to decision-making in a complex therapeutic landscape, the expert panel explores how best to leverage the potency of newer agents across different RCC settings. Upon completion of this activity, participants should be better able to: Assess the latest evidence with and clinical implications of novel approaches, including new targeted agents, immune checkpoint inhibitors, and combination therapies in advanced renal cell carcinoma (RCC), Apply recently validated immunotherapy and targeted therapy options effectively for patients with advanced RCC that reflect optimal patient-centric selection and sequencing through multiple lines of therapy, Employ effective strategies to prevent and/or manage treatment-related complications with multi-targeted TKIs and immune checkpoint inhibitor therapy in patients with RCC, Recommend ongoing clinical trials assessing the latest therapies and/or combination approaches for advanced RCC patients in different disease settings.

Go online to PeerView.com/FEJ860 to view the entire program with slides. In this activity, based on a recent live symposium held at the 2019 Genitourinary Cancers Symposium in San Francisco, experts in renal cell carcinoma (RCC) dip into their patient “CaseBook” to offer insights from their own practice on how best to bridge the divide between clinical research and daily care in the management of RCC. Pairing analysis of the latest evidence with application of key clinical concepts to decision-making in a complex therapeutic landscape, the expert panel explores how best to leverage the potency of newer agents across different RCC settings. Upon completion of this activity, participants should be better able to: Assess the latest evidence with and clinical implications of novel approaches, including new targeted agents, immune checkpoint inhibitors, and combination therapies in advanced renal cell carcinoma (RCC), Apply recently validated immunotherapy and targeted therapy options effectively for patients with advanced RCC that reflect optimal patient-centric selection and sequencing through multiple lines of therapy, Employ effective strategies to prevent and/or manage treatment-related complications with multi-targeted TKIs and immune checkpoint inhibitor therapy in patients with RCC, Recommend ongoing clinical trials assessing the latest therapies and/or combination approaches for advanced RCC patients in different disease settings.

Go online to PeerView.com/FEJ860 to view the entire program with slides. In this activity, based on a recent live symposium held at the 2019 Genitourinary Cancers Symposium in San Francisco, experts in renal cell carcinoma (RCC) dip into their patient “CaseBook” to offer insights from their own practice on how best to bridge the divide between clinical research and daily care in the management of RCC. Pairing analysis of the latest evidence with application of key clinical concepts to decision-making in a complex therapeutic landscape, the expert panel explores how best to leverage the potency of newer agents across different RCC settings. Upon completion of this activity, participants should be better able to: Assess the latest evidence with and clinical implications of novel approaches, including new targeted agents, immune checkpoint inhibitors, and combination therapies in advanced renal cell carcinoma (RCC), Apply recently validated immunotherapy and targeted therapy options effectively for patients with advanced RCC that reflect optimal patient-centric selection and sequencing through multiple lines of therapy, Employ effective strategies to prevent and/or manage treatment-related complications with multi-targeted TKIs and immune checkpoint inhibitor therapy in patients with RCC, Recommend ongoing clinical trials assessing the latest therapies and/or combination approaches for advanced RCC patients in different disease settings.

A special audio program developed from a satellite CME conference held during the 2018 Genitourinary Cancers Symposium featuring expert comments on the application of emerging research to patient care by Charles G Drake, MD, PhD, Peter H O’Donnell, MD, Elizabeth R Plimack, MD, MS, Thomas Powles, MBBS, MRCP, MD and David I Quinn, MBBS, PhD. Moderated by Neil Love, MD. Produced by Research To Practice.

In today’s podcast, Dr. Sumanta Kumar Pal will discuss three studies highlighted at the 2017 Genitourinary Cancers Symposium, including two studies on metastatic kidney cancer and one study on metastatic prostate cancer.  Cancer Research News

Current Strategies and Ongoing Research in the Management of Advanced Prostate Cancer. Proceedings from a CME symposium held at the 2016 Genitourinary Cancers Symposium. Featuring perspectives from Drs Philip Kantoff, William K Oh, Daniel P Petrylak, A Oliver Sartor and Matthew R Smith. Moderated by Dr Neil Love. Produced by Research To Practice.

In today’s podcast, Dr. Sumanta Pal discusses one study highlighted at the 2016 Genitourinary Cancers Symposium that examines whether regular aspirin use lowers the risk of dying from prostate cancer.  Cancer Research News

In today’s podcast, Cancer.Net’s Editor-in-Chief, Dr. Robert Miller talks with patient advocate Wendy Poage about her experience at the 2014 Genitourinary Cancers Symposium. Cancer Research News

In this podcast, we review some of the news announced at the 2014 Genitourinary Cancers Symposium, co-sponsored by ASCO. Cancer Research News

In this podcast, we review some of the news announced at the 2013 Genitourinary Cancers Symposium, co-sponsored by ASCO.

Professor Eleni Efstathiou from MD Anderson Cancer Center, Houston, Texas, USA, and the University of Athens, Greece, summarises for ecancer.TV the latest study findings presented at the 2013 Genitourinary Cancers Symposium, February 14-16, 2013, Orlando, Florida. Professor Efstathiou notes that the third (planned) interim analysis of the COU-AA-302 study has confirmed the benefits of abiraterone in chemotherapy naive, castration-resistant prostate cancer patients with metastatic disease. As well as an increased radiographic progression-free survival, these latest results show the trend towards overall survival (non-significant). No new safety concerns were raised from this prolonged administration analysis, and Professor Efstathiou outlines the implications of these latest findings to physicians. Professor Efstathiou comments on the negative study results from READY and VENICE trials, and offers an explanation for these results. She also outlines a new study assessing the combination of abiraterone and enzalutamide, and the markers being used to assess efficacy and outcomes in this study. Professor Efstathiou discusses the extensive collaborations between institutions to identify markers of efficacy and disease progression in this current period of considerable drug development. She also advises on what and how physicians should currently be prescribing in clinical practice. In her take-home message to physicians, Professor Efstathiou stresses that mCRPC is largely androgen-dependent castration resistant and that the tumour microenvironment determines how the tumour responds to agents; thereby explaining the opportunities offered by the newer agents targeting androgen signalling before moving on to a chemotherapeutic agent.

Professor Kurt Miller, Head of Urology, Charité Universitätsmedizin, Berlin, Germany, talks to ecancer.TV about the data presented at the 2013 Genitourinary Cancers Symposium on mCRPC. Professor Miller expresses excitement about the wide variety of drugs being explored in mCRPC. He points to the latest results of the AFFIRM study with enzalutamide showing positive quality of life data, and emphasises the importance of quality of life data in this patient group. He also notes the data from the Cougar 301 and Cougar 302 studies with abiraterone acetate. He then outlines the key data from the AFFIRM and Cougar 301 and 302 studies, and outlines the differences between abiraterone and enzalutamide. Professor Miller advises physicians on the use of these two agents (as well as their potential use in combination), and of additional new agents on the horizon. In terms of challenges for physicians treating patients with mCRPC, Professor Miller notes the importance of determining response criteria, progression criteria, choice and order of drug therapies.

Professor Karim Fizazi, Head of the Department of Cancer Medicine at the Institut Gustave Roussy, Villejuif, France, and Full Professor in Oncology, University of Paris, France, talks to ecancer about the hottest results presented at the 2013 Genitourinary Cancers Symposium. Starting with the main studies with a negative outcome, he outlines two large phase III studies; one with aflibercept, and the other with dasatinib. Explaining the negative results of the VENICE study (multinational phase III trial examining the efficacy of aflibercept versus placebo in combination with docetaxel/prednisone for first-line treatment of mCRPC), Professor Fizazi suggests that angiogenesis is not a major factor in prostate cancer. As for the negative results from the READY trial (randomised phase III trial examining overall survival and safety of dasatinib/docetaxel versus docetaxel in patients with metastatic castration-resistant prostate cancer (mCRPC), Professor Fizazi suggests that dasatinib is more a bone-targeting agent than an cancer-targeting agent. Outlining the main positive study results, Professor Fizazi points to the new generation endocrine therapies, such as abiraterone acetate. For this agent, the results of the third interim analysis presented from the COU-AA-302 randomised phase III study of abiraterone acetate in chemotherapy naive patients with mCRPC showed positive results. Also, more results from the AFFIRM study with enzalutamide in patients with more advanced disease, in patients with and without corticosteroids. Professor Fizazi also comments on the use of corticosteroids with abiraterone and enzalutamide. Professor Fizazi shares his views on the use of abiraterone and enzalutamide in patients with mCRPC in terms of when and how they should be used. He comments on toxicity, symptom improvement, overall survival improvement and effects on quality of life of these two newer agents. Finally, Professor Fizazi shares his views on the early results with the new androgen-receptor inhibitors, ODM-201 and ARN-509. These agents add to the physicians’ currently growing armamentarium of agents for mCRPC.

In this podcast, we review some of the news announced at the 2013 Genitourinary Cancers Symposium, co-sponsored by ASCO. Cancer Research News

Nicholas Vogelzang, MD, discusses the research highlights from the 2012 Genitourinary Cancers Symposium in San Francisco, California, including research on prostate cancer. Cancer Research News

Nicholas Vogelzang, MD, discusses the research highlights from the 2011 Genitourinary Cancers Symposium in Orlando, Florida, including research on prostate cancer. Cancer Research News

Host: Mark Chyna, MD Listen to the latest research presented at the American Society of Clinical Oncology's 2010 Genitourinary Cancers Symposium, held March 5 - 7 in San Francisco, California, including findings on prostate, penile and bladder cancer.