Podcasts about asco gu

En este episodio, Brian, Tom y Matt Galsky analizan los datos del estudio B15 sobre terapia neoadyuvante para el cáncer de vejiga músculo-invasivo cisplatino-elegible, centrándose en la eficacia de EV-Pembro en comparación con cisplatino-gemcitabina. Exploran la SLE, SG y las implicaciones de la duración del tratamiento así como su individualización. La conversación también aborda el papel del ctDNA en las decisiones terapéuticas, las histologías alternativas y la importancia de la terapia sistémica neoadyuvante. El episodio concluye con reflexiones sobre las futuras direcciones en el tratamiento del cáncer de vejiga y la relevancia de los estudios en curso.

En este episodio se abordan los resultados más recientes del ensayo fase 3 LITESPARK 011 (belzutifan + lenvatinib frente a cabozantinib). Brian, Tom y Bob Motzer analizan la eficacia, seguridad y las implicaciones de los resultados para la secuenciación de tratamiento.

En esta discusión se exploran los últimos avances en el tratamiento adyuvante del cáncer de riñón, centrándose en los recientes resultados del ensayo fase 3 de belzutifan en combinación con pembrolizumab (LITESPARK-022). Se abordan los pormenores del mecanismo de acción, el desarrollo de biomarcadores y futuras direcciones y líneas de investigación.

En este episodio, Evan Yu analiza los datos más recientes sobre cáncer de próstata presentados en ASCO GU, centrándose en los resultados finales de SG del ensayo PEACE-3, las implicaciones del cruce en las curvas de supervivencia y el papel de la terapia con radioligandos e inhibidores de PARP en el tratamiento del cáncer de próstata. 

La conversación gira en torno al ensayo Sunrise 2, un estudio que investiga la eficacia de TAR-200 combinado con cetrilimab frente a quimiorradioterapia convencional en cáncer de vejiga músculo-invasivo. La discusión aborda el diseño del estudio, la población elegida, los resultados y las implicaciones para futuras estrategias terapéuticas, destacando la importancia de la selección de pacientes y el potencial de TAR-200 en etapas más tempranas del tratamiento.

Brian, Silke and Tom discusses the latest data and insights from ASCO GU 2026 across kidney, prostate, and bladder cancer, highlighting new therapies, trial results, and future directions in urologic oncology.

Dr. Aly-Khan Lalani and Dr. Christopher Wallis also highlight Canadian-led innovation in the GUNS trial and early data from the PAnTHA study, and discuss how Prostate Cancer Working Group 4 may redefine trial design. Episode 35 is the first of three ASCO GU recap episodes, so don't miss Episode 36 on bladder cancer and Episode 37 on kidney cancer!The View on GU with Lalani & Wallis integrates key clinical data from major conferences and high impact publications, sharing meaningful take home messages for practising clinicians in the field of genitourinary (GU) cancers. Learn more about The View on GU: theviewongu.caThis podcast has been made possible through unrestricted financial support by Pfizer, Tolmar, AbbVie, Astellas, Eisai, Ipsen, Merck, Bayer, TerSera.

Dr. Aly-Khan Lalani and Dr. Christopher Wallis also discuss the RAMPART trial, LITESPARK-011, and the K-COMPASS model. This final recap episode highlights how evolving adjuvant strategies and combination sequencing are reshaping the kidney cancer landscape. Be sure to listen to Episodes 35 and 36 for the full ASCO GU recap, covering key updates in prostate and bladder cancer!The View on GU with Lalani & Wallis integrates key clinical data from major conferences and high impact publications, sharing meaningful take home messages for practising clinicians in the field of genitourinary (GU) cancers. Learn more about The View on GU: theviewongu.caThis podcast has been made possible through unrestricted financial support by Pfizer, Tolmar, AbbVie, Astellas, Eisai, Ipsen, Merck, Bayer, TerSera.

Dr. Aly-Khan Lalani and Dr. Christopher Wallis discuss practice-changing data in non-muscle invasive and muscle-invasive bladder cancer, including perioperative strategies,bladder-sparing approaches, and emerging targeted therapies. Don't forget to watch or listen to Episode 35 and Episode 37 for updates on prostate and kidney cancer!The View on GU with Lalani & Wallis integrates key clinicaldata from major conferences and high impact publications, sharing meaningful take home messages for practising clinicians in the field of genitourinary (GU) cancers. Learn more about The View on GU: theviewongu.caThis podcast has been made possible through unrestricted financial support by Pfizer, Tolmar, AbbVie, Astellas, Eisai, Ipsen, Merck, Bayer, TerSera.

This week discuss BR.31 trial of adjuvant durvalumab in NSCLC and put it into the context of the positive studies with atezolizumab and pembrolizumab. We also highlight 2 notable presentations at ASCO GU 2026 on perioperative enfortumab vedotin + pembrolizumab in cisplatin-eligible patients with resectable bladder cancer (KEYNOTE-B15) and advjuant pembrolizumab + belzutifan in RCC (LITESPARK-022) Check out the Oncology Insights Newsletter: https://www.kelleycpharmd.com/newsletter-oncopharm

Dr. Monty Pal and Dr. Andrea Apolo discuss practice-changing studies and other novel approaches in bladder, kidney, and prostate cancers that were presented at the 2026 ASCO Genitourinary Cancers Symposium. TRANSCRIPT Dr. Monty Pal: Hello and welcome to the ASCO Daily News Podcast. I'm your host, Dr. Monty Pal. I'm a medical oncologist, professor and vice chair of academic affairs at the City of Hope Comprehensive Cancer Center in Los Angeles.  And today is super exciting, we're highlighting key abstracts that were presented at the 2026 ASCO GU Cancers Symposium, and I'm just delighted to be joined by the chair of this year's meeting, who is also a dear friend, Dr. Andrea Apolo. Dr. Apolo serves within the Center for Cancer Research at the NCI as head of the Bladder Cancer Section, and she is also acting deputy chief of the Genitourinary Malignancies Branch.  Welcome, Andrea, it is so great to have you on the podcast. Dr. Andrea Apolo: Oh, thank you so much for having me. What a great ASCO that we had, it is really exciting, lots of really great data. So I look forward to chatting about it. Dr. Monty Pal: Excellent. And you know, our full disclosures are available in the transcript of this episode in case our listeners want to have a peek.  The theme of this year's GU meeting was "Patient-Centered Care: From Discovery to Delivery." I love that theme. And really, this is one of the most competitive meetings out there, more than 850 abstracts being presented on high-impact science. Andrea, I just wanted to get right into it and dive into what I think we both felt were some of the most exciting abstracts of the meeting.  And the first of those is one that I know is near and dear to your heart, being a bladder cancer expert yourself, and that is the KEYNOTE-B15 study presented by Matt Galsky. Can you give us a flavor for what that study entailed and some of the key results? Dr. Andrea Apolo: Yeah, I think this was kind of the missing study that we have been waiting for since we saw the EV-302 data in metastatic disease in the frontline setting. We wanted to know how well this combination would work in muscle-invasive bladder cancer patients. And we saw half of that puzzle, you can say half of the piece of the puzzle, when we saw the data at ESMO, the EV-303 data in patients that were cisplatin-ineligible. And then now we are getting the full story with patients that are platinum-eligible, cisplatin-eligible, with the EV-304 data. So that study randomized patients to receive chemotherapy, so different than the EV-303 where the patients were randomized just to receive the radical cystectomy. These patients were randomized to receive neoadjuvant EV plus pembro and then adjuvant EV plus pembro versus neoadjuvant gemcitabine and cisplatin with no adjuvant component to the control arm. So I think this is a really, really important study. Dr. Monty Pal: And share with us some of the results because this in my mind is definitely practice-changing. This is one of those studies that I think you walked into the office on Monday and you are like, "Okay, this is what I am doing now," right? Dr. Andrea Apolo: Yeah. So the study was positive. The primary endpoint was event-free survival, and it met the primary endpoint. The secondary endpoint of overall survival was also met. So really, really great results. Consistent with what we saw with EV-303, the median event-free survival was not reached for the EV plus pembro arm, and it was 48 months for the patients receiving gem-cis. And then looking at the 24-month estimated event-free survival, it was 79% for the EV plus pembro and 66% for the chemo, the gem-cis arm. And that was a hazard ratio of 0.5. So that is really exciting. That is the event-free survival. And then the overall survival, the medians were not reached for either arm, but when you look at the 24-month estimated overall survival, it was 87% for the EV plus pembro versus 81% for the gem-cis, and that was a hazard ratio of 0.65. So very positive study.  And then another question that we had was the pathologic CR rate. Very consistent with what we saw with the EV-303, the pathologic response rate was about 56% for the patients that received EV plus pembro and about 32%, 33% for the patients that received gem-cis. So very consistent with the findings that we have been kind of seeing in phase 2 studies, and this is a pT0N0, so that is important. Dr. Monty Pal: So Andrea, you know, I think that the big question in folks' minds is at this point, we see the data from NIAGARA, cis-gem-durva, we have now seen this data. Put it into context for us. Is there a patient in this day and age who maybe shouldn't get IO altogether, who should maybe get the NIAGARA regimen as opposed to EV-pembro in this context? What are your thoughts there? Dr. Andrea Apolo: Now, that is a great question. I would say with this data, it is very enticing to give EV pembro to our patients in the perioperative setting, and for that to be the new standard of care for all patients, regardless of cisplatin eligibility. So similar to what we saw with EV-302 really changing the standard of care in the frontline setting, I think these two studies, the EV-303 and the EV-304, change the standard of care for patients with muscle-invasive bladder cancer in the perioperative setting, and this should be the new standard of care if the patients don't have a restriction to receiving an immunotherapy. Dr. Monty Pal: I totally agree with that assessment. It is great to hear it from the expert's mouth as well. Thanks a lot for that, Andrea.  The next abstract I wanted to tackle is one that is, I would say, near and dear to my heart because I know these folks really well. It is led by the SWOG group, and this is SWOG S1602. The number there for the audience gives you a sense of how long the study has been running for. The 16 prefix means it is something that we kicked off back in 2016. So this study is really 10 years in the making, right? So Rob Svatek presented this data. It is interesting, right, because it addresses this issue of the BCG (Bacille Calmette-Guérin) shortage, right, where we have needed to sort of rely potentially on other alternative sources or regimens and so forth. Tell us about this trial, Andrea. Dr. Andrea Apolo: This is one of my favorite studies. We talked about putting it in the main oral abstracts, but we put it in one of the educational sessions that talked about non-muscle-invasive bladder cancer because we thought that would be the best audience for it. But it doesn't take away from how important this abstract is, and the tremendous effort that went into the study. Almost a thousand patients enrolled. I think 984 were eligible to enroll in this study. So it is a very high enrolling, randomized, cooperative group study in high-grade non-muscle-invasive bladder cancer. And really the study was designed to address two questions. One is the BCG shortage and can we use a different strain, Tokyo versus TICE? And whether there is a priming effect if you gave intradermal BCG to patients with non-muscle-invasive bladder cancer, can that enhance the effect if you gave it a little bit earlier? I think the study is really important, and it met its primary endpoint, which was it is not inferior to TICE. The findings were really terrific in terms of the outcomes. Numerically. When you look at the endpoint, it looked like the Tokyo strain was as good, if not maybe a little bit better, but not statistically significant than the TICE. And then they broke it down by carcinoma in situ, they broke it down by papillary tumors, and the Tokyo strain was non-inferior in both of those instances. But interestingly, the intradermal BCG did not change outcomes. There was really no priming effect, which was really backed up by pre-clinical data that there would be, but there wasn't a priming effect when the intradermal BCG was given in the Tokyo strain. So that was a really, really interesting finding. But a great study, really important outcomes in the field for non-muscle-invasive bladder cancer. Dr. Monty Pal: Totally. And it just seems like we can't get away from BCG, right? You know, as hard as we try, I mean, I appreciate the studies that sort of build on it that are emerging right now, but it seems like BCG at least for the foreseeable future is kind of here to stay, right? Dr. Andrea Apolo: It works. It is one of the most effective treatments we have for non-muscle-invasive bladder cancer. So, you know, I think it is here to stay and, you know, we need to find alternatives in terms of strains so we don't deal with this shortage that we have been dealing with for so many years now. Dr. Monty Pal: Yeah, indeed. Moving on to some of the other highlighted studies from the meeting, you had mentioned the EV-303 data, so we probably don't need to rehash that study design in much detail. But there was also a rapid oral abstract presented by Dr. Ullén that I think is of interest here, right, that really hones in on pathologic outcomes and DFS from that trial. Do you mind just outlining that for our listenership? Dr. Andrea Apolo: This is the KEYNOTE-905, also known as the EV-303 study. This is a follow-up to the EV-303 data looking at the pathologic response rates, looking at the downstaging effect, looking at the surgical margins after treatment with the neoadjuvant EV plus pembro in the 303. Now, remember in the 303, patients got three cycles of neoadjuvant EV plus pembro and then six cycles in the adjuvant setting. A little bit different than the 304, where they got four cycles, which is really kind of the standard in the neoadjuvant setting, and then five cycles in the adjuvant setting. So still a total of nine cycles. But in the 303, the treatment arm had no systemic therapy, so it was just radical cystectomy. And they looked at the negative margins that you get with the EV plus pembro treatment, which was 92.6% versus 79% with patients receiving just the surgery alone. And then the pathologic CR rate, there was more follow-up on that, it was 57% for the patients receiving EV plus pembro, and as we would expect, about 9% for the patients that just went on to surgery alone because you can achieve a pathologic response rate with TURBT alone. Then they looked at the pathologic downstaging, so anything less than a pT2, and that was 66% in the patients that received the EV plus pembro. So very interesting findings, and it is also really just nice to have now the EV-304 data, like I was saying, there were two pieces of it, the cisplatin-eligible and the cisplatin-ineligible, and just to have those contemporary controls are really important. How did the cisplatin-ineligible do versus the cisplatin-eligible patient in terms of the event-free survival and in terms of the overall survival? So I feel like now we have all of this data that we can kind of put together in the perioperative setting and we can really inform our patients a little bit more about their outcomes depending on whether they are cisplatin-eligible or not, which you know cisplatin-ineligible patients often just, they are sicker, they may have obstruction, their tumors may be larger, they just tend to be a more delicate population than the cisplatin-eligible patients. So not surprisingly, you know, we see that in the EV-303 the disease-free survival for the patients is pretty poor. So the disease-free survival that was reported for this follow-up of the specific abstract was 23.6 months for the patients that just got surgery, and it was not reached for the patients that had the EV plus pembro, and that was a hazard ratio of 0.37. Dr. Monty Pal: Excellent, excellent distillation. So Andrea, in the interest of time, I mean, we could probably talk about bladder cancer forever, but I am going to move us on to the subject of kidney cancer. We have two late-breaking abstracts, LITESPARK-011, which looked at lenvatinib and belzutifan versus cabozantinib in the advanced setting, and then we have an adjuvant study, LITESPARK-022, that looked at pembrolizumab with or without belzutifan in the adjuvant setting. Both studies positive. One for progression-free survival, the other for disease-free survival. Both I think making a big dent in how we treat kidney cancer. Can you tell us a little bit about that? Dr. Andrea Apolo: Yeah, we have been waiting for these trials for a long time. So one of the things that we have been talking about at GU ASCO is to have plenary sessions. And if we would have had a plenary session, these two abstracts would have been part of it because they are important data, really big studies where we are trying to improve the outcomes of our patients with kidney cancer. So the first one, the LITESPARK-011, like you said, this is for advanced renal cell carcinoma, clear cell renal cell carcinoma, where we really don't have a standard of care after IO therapy, right? So we give IO-IO, we give VEGF-IO, but we don't really have a good standard of care. We usually give monotherapy TKIs. So the combination of belzutifan and lenvatinib versus what a standard of care is, cabozantinib, is really an important question to ask. And you know, this is a pretty large study, about 750 patients were randomized. And belzutifan plus lenvatinib demonstrated an improvement in progression-free survival and overall survival versus cabozantinib, but not overall survival, at least not yet, is what the authors are saying. So for the progression-free survival, the hazard ratio was 0.7 and it was 14.8 months for the combination, belzutifan plus lenvatinib arm versus cabozantinib, which was 10.7 months. So I think that is significant. And for the overall survival, it did favor the combination again with a hazard ratio of 0.85. The median was 35 months versus 28 months for the monotherapy cabozantinib, but it did not reach statistical significance. And the authors said that this will be further tested at a final analysis, these were the interim results.  And for the overall survival, the overall survival was 53% for the combination versus 40%. This is significant. And the CR rates were lowish for both of them, it was like 5% for the combo and 1% for cabo monotherapy. So I think that the findings are important because we don't have a standard of care. And although there is no survival benefit, there was a trend. So I think this could be considered in patients that are fit, a treatment option for these patients in the later line settings. Dr. Monty Pal: Great points. I mean lots of great discussion around toxicity as well as efficacy. I mean certainly this is a regimen that may not be suitable for every patient in my portfolio, but certainly one to consider.  Now Andrea, let's shift focus to LITESPARK-022, the adjuvant trial that I mentioned previously. So this is again looking at pembrolizumab with or without belzutifan, met the primary endpoint of disease-free survival. What are your impressions there of the data? Dr. Andrea Apolo: Yeah, the data looks great. And this was a really large study, 1,800 patients were randomized, and the study met the primary endpoint of disease-free survival, benefiting the combination of pembro plus belzutifan. And that is really terrific. The medians were not reached for either arm. And in terms of the overall survival results, also the medians were not reached, but the hazard ratio was 0.78 and did not reach a statistical significance. So there was again a statistically significant improvement in disease-free survival for the combination of pembrolizumab plus belzutifan, but not an overall survival benefit.  So I guess, Monty, you know, we can kind of talk about what that means. There was a lot of discussion about belzutifan and some of the side effects, specifically anemia and managing anemia in this setting and requirements for transfusions. Generally, the authors said it was well tolerated, but we know that combination studies do have more toxicity. So it may be a select group of patients again, similar to the advanced setting, where we opt for a combination, possibly until we see more follow-up data in terms of the overall survival. Dr. Monty Pal: I have to agree with you. You know, in my group, we have been talking about a lot of pembrolizumab-based studies that are running right now, some through the NCI, some, you know, our own sort of homegrown investigator-sponsored trials, and you know, I think for the foreseeable future we are comfortable just maintaining pembrolizumab. Things might change if, for instance, we ultimately see a survival advantage emerge, but I just have my own personal doubts around that, that will be interesting.  Okay, so now we are going to move to the last disease category that we are going to cover, which is prostate cancer. So there, we have the long-awaited results from the PEACE-3 study. These are the final OS results from this trial looking at enzalutamide with or without radium-223 in metastatic castration-resistant prostate cancer. So Andrea, would love to get your perspectives on this. Dr. Andrea Apolo: Yeah, so this study had been presented before and we had seen positive results for the combination of enzalutamide and radium with some interim overall survival results also showing a benefit. But like you said, these are the final results with a median follow-up of 58 months. So it was really nice to see the final results. And with the combination of enzalutamide and six cycles of radium, it did show an improvement in overall survival with a hazard ratio of 0.76. The median overall survival increased from 32.6 months to 38.2 months with the combination. So that is really great. There was some crossing over of the overall survival curves around 18 months was still seen. And again, there was also an improvement in the rPFS with a hazard ratio of 0.71, and the median rPFS improved from 16.4 to 19 months with the combination. So, you know, we have been awaiting the final results, but we kind of knew a lot about the benefits of the combination. And it is something that is kind of slowly trickling into the community in terms of adapting it and using it. There is more buzz now about it and I think these overall survival results will hopefully shift the community into incorporating the combination in these patients. Dr. Monty Pal: Brilliant. So well said. I mean, Andrea, congratulations on a terrific meeting. You have really done it again. Incredible, incredible output from this year's ASCO GU. I just want to thank you for joining us on the program today. Dr. Andrea Apolo: Oh, thank you so much for having me, Monty. It was really a joy to work with the ASCO team and with all the investigators and the Education Committee and the Scientific Committee. Everyone was really outstanding. So to me it was an honor to be part of this meeting, and I am so happy that it was so successful and really presented some amazing data that I think will be practice-changing to our patients. Dr. Monty Pal: Oh, thanks a ton. And also a huge thanks to our listeners. If you enjoyed the content of today's podcast, please don't forget to like and subscribe to our channel wherever you listen to podcasts. Thanks so much. Disclaimer: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Follow today's speakers:     Dr. Monty Pal   @montypal  Dr. Andrea Apolo @apolo_andrea  Follow ASCO on social media:          ASCO on X    ASCO on Bluesky         ASCO on Facebook          ASCO on LinkedIn          Disclosures:       Dr. Monty Pal:      Speakers' Bureau: MJH Life Sciences, IntrisiQ, Peerview     Research Funding (Inst.): Exelixis, Merck, Osel, Genentech, Crispr Therapeutics, Adicet Bio, ArsenalBio, Xencor, Miyarsian Pharmaceutical     Travel, Accommodations, Expenses: Crispr Therapeutics, Ipsen, Exelixis     Dr. Andrea Apolo: No disclosures to report.

In this episode, UROONCO BCa chief editor Dr Benjamin Pradere (France) sits down with Matthew Galsky, Professor of Medicine at Icahn School of Medicine at Mount Sinai (New York, USA), to discuss the newly published results of the KEYNOTE-B15 trial.This marks a truly pivotal moment for muscle-invasive bladder cancer. The presentation of KEYNOTE-B15 represents one of the most practice-changing advances in localised MIBC management in recent years, opening a new era of peri-operative systemic therapy and renewed hope for our patients.KEYNOTE-B15 is a randomised phase III trial evaluating peri-operative enfortumab vedotin plus pembrolizumab in cisplatin-eligible patients with MIBC. In this in-depth discussion, Prof. Galsky walks us through the scientific rationale behind the study, the key efficacy and safety results, and crucially, how these data are likely to reshape clinical practice, not only in the immediate future but for years to come.A must-listen conversation for urologists and multidisciplinary teams involved in the care of bladder cancer patients.The KEYNOT-B15 study will be also presented and discussed at upcoming EAU26 on Saturday 14th March in the Game Changer Session. Don't miss the chance to hear more on this important study and mark your agenda! This interview was recorded at ASCO GU26. For more updates on bladder cancer, please visit our educational platform UROONCO BCa.For more EAU podcasts, please go to your favourite podcast app and subscribe to our podcast channel for regular updates: Apple Podcasts, Spotify, EAU YouTube channel.

The conversation revolves around the Sunrise 2 trial, a study investigating the efficacy of TAR-200 combined with cetrilimab versus traditional chemoradiotherapy in muscle-invasive bladder cancer. The discussion covers the study's design, patient population, results, and implications for future treatment strategies, emphasizing the importance of patient selection and the potential for TAR-200 in earlier treatment settings.

This in-depth discussion explores the latest advancements in adjuvant kidney cancer treatment, focusing on the recent phase 3 trial results of Belzutifan combined with Pembrolizumab, mechanistic insights, biomarker development, and future research directions.

summaryThis detailed discussion covers the latest phase three trial results in kidney cancer, focusing on LITESPARK 011: Belzutifan and Levatnib combination versus Cabozantinib. Brian, Tom and Bob Motzer analyze efficacy, safety, and implications for treatment sequencing.

In this podcast , Brian, Tom and Matt Galsky discuss the B15 study data on neoadjuvant therapy for muscle invasive bladder cancer, focusing on the efficacy of EV Pembro compared to gem-cis. They explore event-free survival, overall survival, and the implications of treatment duration and individualization. The conversation also touches on the role of ctDNA in treatment decisions, alternative histologies, and the importance of neoadjuvant systemic therapy. The hosts conclude with reflections on future directions in bladder cancer treatment and the significance of ongoing studies.

In this episode, Evan Yu discusses the latest prostate cancer data presented at ASCO GU, focusing on the final overall survival results of the PEACE 3 trial, the implications of crossing survival curves, and the evolving role of radioligand therapy and PARP inhibitors in prostate cancer treatment.

Two Onc Docs, hosted by Samantha A. Armstrong, MD, and Karine Tawagi, MD, is a podcast dedicated to providing current and future oncologists and hematologists with the knowledge they need to ace their boards and deliver quality patient care. Dr Armstrong is a hematologist/oncologist and assistant professor of clinical medicine at Indiana University Health in Indianapolis. Dr Tawagi is a hematologist/oncologist and assistant professor of clinical medicine at the University of Illinois in Chicago.In this episode, OncLive On Air® partnered with Two Onc Docs to highlight anticipated data from the upcoming 2026 Genitourinary Cancers Symposium, noting presentations to watch at sessions on prostate cancer, bladder cancer, and renal cell carcinoma (RCC).For prostate cancer, the experts revealed that they're looking forward to seeing updated results from the phase 3 PEACE-3 trial (NCT02194842) of enzalutamide (Xtandi) plus radium-223 in patients with metastatic castration-resistant prostate cancer (mCRPC), noting that bone-protecting agents are mandatory for patients receiving radium-223. They also pointed to overall survival data from the phase 2 BRCAAway trial (NCT03012321) of abiraterone (Zytiga) plus prednisone and olaparib (Lynparza) for patients with mCRPC harboring BRCA or ATM alterations. Additionally, they spotlighted the phase 3 PEACE 2 trial (NCT01952223), which explores moving chemotherapy into the localized prostate cancer setting.Regarding bladder cancer, they identified the phase 3 KEYNOTE-B15 trial (NCT04700124) as a potentially practice-changing trial evaluating perioperative enfortumab vedotin-ejfv (Padcev) plus pembrolizumab (Keytruda) in cisplatin-eligible patients with muscle-invasive bladder cancer. They also noted that circulating tumor DNA data are a significant trend, appearing in several clinical trials to guide response-adapted management.For RCC, the hosts highlighted the phase 3 LITESPARK-011 (NCT04586231) and LITESPARK-022 (NCT05239728) trials, which are evaluating the HIF-2α inhibitor belzutifan (Welireg) in different RCC populations. They also emphasized the importance of the CLIMATE study (ACTRN12622000247774) for detecting residual disease in patients with testicular cancer.

This week's episode we discuss what to look forward to at ASCO GU this week. Held in SF Feb 26-28 in San Francisco. We will go over the program in prostate cancer, kidney cancer, bladder cancer, as well as testicular cancer.

Host Dr. Davide Soldato and guests Dr. David Einstein and Dr. Ravi Madan discuss JCO article, "National Cancer Institute's Working Group on Biochemically Recurrent Prostate Cancer: Clinical Trial Design Considerations," underscoring the need for a consensus on clinical trial designs implementing novel endpoints in this population, the importance of PSA doubling time as a prognostic factor and with an emphasis on treatment de-escalation to limit toxicity and improve patient outcomes. TRANSCRIPT The disclosures for guests on this podcast can be found in the show notes. Davide Soldato: Hello and welcome to JCO After Hours, the podcast where we sit down with authors from some of the latest articles published in the Journal of Clinical Oncology. I am your host, Dr. Davide Soldato, medical oncologist at Ospedale San Martino in Genoa, Italy. Today, we are joined by JCO authors Dr. David Einstein and Dr. Ravi Madan. Dr. Einstein is a medical oncologist specializing in genitourinary malignancy working at Beth Israel Deaconess Medical Center, part of the DFCI Cancer Center, and an assistant professor at Harvard Medical School. Dr. Madan is a senior clinician at the National Cancer Institute (NCI), where he focuses on conducting clinical research in prostate cancer, particularly in the field of immunotherapy. Today, we will be discussing the article titled, "National Cancer Institute's Working Group on Biochemically Recurrent Prostate Cancer: Clinical Trial Design Considerations." So, thank you for speaking with us, Dr. Einstein and Dr. Madan. David Einstein: Thanks for having us. This is a great pleasure. Ravi Madan: Appreciate being here. Davide Soldato: So, I just want to start from a very wide angle. And the main question is why did you feel that there was the need to convey a consensus and a working group to talk about this specific topic: biochemically recurrent prostate cancer? What has been the change in current clinical practice and in the trial design that we are seeing nowadays? And so, why was it necessary to convey such a consensus and provide considerations on novel clinical trials? David Einstein: Yeah, so I think it's very interesting, this disease state of biochemically recurrent prostate cancer. It's very different from other disease states in prostate cancer, and we felt that there was a real need to define those differences in clinical trials. Years ago, metastatic castration-resistant prostate cancer was the primary disease state that was explored, and over time, a lot of things shifted earlier to metastatic disease defined on a CAT scan and bone scan to an earlier disease state of metastatic castration-sensitive prostate cancer. And the clinical trial principles from late-stage could be applied to MCSPC as well. However, BCR is very different because the patients are very different. And for those reasons, there are unique considerations, especially in terms of toxicity and treatment intensity, that should be applied to biochemically recurrent prostate cancer as opposed to just using the principles that are used in other disease states. And for that reason, we thought it was very important to delineate some of these considerations in this paper with a group of experts. Davide Soldato: Thanks so much. So, one of the main changes that have been applied in recent years in clinical practice when looking at biochemically recurrent prostate cancer is the use of molecular imaging and particularly of PSMA PET. So, first of all, just a quick question: was the topic of the consensus related on which threshold of PSA to use to order a PET scan to evaluate this kind of patient? David Einstein: Yeah, thanks for that question. It's a super important one. The brief answer is that no, we did not address questions about exactly when clinicians would decide to order scans. We were more concerned with the results of those scans in how you define different disease states. But I think as a broader question, I think a lot of folks feel that finding things on a scan equates that with what we used to find on conventional scans. And fundamentally, we actually sought to redefine that disease space as something that's not equivalent to metastatic disease, and rather coined the term "PSMA-positive BCR" to indicate that traditional BCR prognostic criteria and factors still apply, and that these patients have a distinct natural history from those with more advanced metastatic disease. Ravi Madan: And if I may just add that the National Cancer Institute is running a trial where we're prospectively monitoring PSMA-positive BCR patients. And that data is clearly showing that, much like what we knew about BCR a decade ago, PSMA findings in BCR patients do not change the fact that overall, BCR is an indolent disease state. And the findings, which are usually comprised of five- to seven-millimeter lymph nodes, do not endanger patients or require immediate therapy. And so, while PSMA is a tool that we can be using in this disease state, it doesn't really change the principal approach to how we should manage these patients. And as Dr. Einstein alluded to, there is a drive to create a false equivalency between PSMA-positive BCR and metastatic castration-sensitive prostate cancer, but that is not supported by the data we're accumulating or any of the clinical data as it exists. Davide Soldato: One thing that it's very important and you mentioned in your answer to my question was actually the role of PET scan and conventional imaging, so CAT scan and bone scan that we have used for years to stage patients with metastatic prostate cancer. And you mentioned that there is a distinction among patients who have a positive PET scan and a BCR, and patients who have a positive conventional imaging. And yet, we know that sometimes the findings of the PET scan are not always so clear to interpret. So, I just wanted to understand if the consensus reached an agreement as to when to use conventional imaging to potentially resolve some findings that we have on PET scan among thess patients with BCR? David Einstein: Yeah, I think there's a number of questions actually buried within that question. One of which is: does PSMA PET result in false positives? And the answer has definitely been yes. There's a known issue with false-positive rib lesions. And so, first and foremost, we need to be very careful in calling what truly is suspicious disease and what might actually not be cancer or might be something that is totally separate. So I think that's the first part of the answer to that question. The second is to what extent do we need to use paired PET and conventional imaging to define this disease state? In other words, do you have to have positive findings on one and negative findings on the other in order to enter this definition? The challenge there, as we discussed, is that logistically, oftentimes it's hard to get patients to do multiple sets of scans to actually create that definition. Sometimes it's difficult to get insurers to pay for such scans. And finally, it's hard to sometimes blind radiologists to the results of one scan in reading the other. So, we did have some deliberations about to what extent you could use some of the CAT scan portion of a PSMA PET in order to at least partially define that. We also talked about using bone scans to confirm any bone findings seen on PET. But I think another important part of this is not just the baseline imaging, but also what's going to be done serially on a study in order to define responses and progression. And that's sort of a whole separate conversation about to what extent you can interpret changes in serial PET. Ravi Madan: And just to pick up on the key factor here, I think that the PSMA PET in BCR is pretty good at defining lymph node disease, and that's actually predominantly 80 to 90 percent of the disease seen on these findings. It might be pretty good at also defining other soft tissue findings. The real issues come to bone findings. And one thing the group did not feel was appropriate was to just define only PSMA-positive bone findings confirmed on a CT bone window. There's not really great data on that, but the working group felt that, when in the rare situation, because it is relatively rare, a PSMA-positive finding is in a bone, a bone scan should be done. And it's worth noting that Phu Tran, who is a co-author and a co-leader of this working group, his group has already defined that underlying genomics of conventionally based lesions, such as bone scan, are more aggressive than findings on next-gen imaging, such as PSMA. So, there is also a genomic underlying rationale for defining the difference between what is seen on a PET scan in a bone and what is seen on a bone scan. Davide Soldato: Coming back to this issue of PET PSMA sometimes identifying very small lesions where we don't see any kind of correlates on conventional imaging or where we see only very little alteration on the bone scan or in the CT scan, was there any role that was imagined, for example, for MRI to distinguish this type of findings on the PET scan? Ravi Madan: So, I think that, again, what can be identified on a PSMA frequently cannot be seen on conventional imaging. We didn't feel that it was a requirement to get an MRI or a CT to necessarily confirm the PSMA findings. I think that generally, we have to realize that in this disease state, that questionable lesions are going to be seen on any imaging, including PSMA. We've actually probably put way too much faith in PSMA findings thus far, as Dr. Einstein alluded to with some of the false positives we're seeing. So, I think that these false positives are going to have to be baked into trials. And in terms of clinical practice, it highlights the need to again, not overreact to everything we see and not necessarily need to biopsy everything and put patients' health in jeopardy to delineate a disease that's indolent anyway. Davide Soldato: Thanks so much. That was very clear. So, basically, the main driver was really also the data showing that if we have a BCR, so a patient with a biochemically recurrent disease that is positive on the conventional imaging, this is usually associated with a different aggressiveness of the disease. But coming back to a comment that you made before, Dr. Madan, you said that even if we talk about PSMA-positive BCR, we are still talking about BCR and the same criteria should apply. So, what we have used for years in this space to actually try to stratify the prognosis of patients is the PSA doubling time, so how quickly the PSA rises over time. So, coming back to that comment, was the consensus on the PSA doubling time basically retained as what we were using before, so defining patients with a doubling time less than 12 months, 10 months, 9 months, as patients with a higher risk of progressing in terms of developing metastatic disease? Ravi Madan: Yes, so that's a very important point. And the working group defined high-risk BCR as a PSA doubling time less than six months. And this really comes from Johns Hopkins historical data, which shows that if your doubling time is three months or less, there's about a 67 percent chance of metastasis at five years. If it's between three and six months, it's 50 percent. And if it's over six months, if it's between six and nine months, it's roughly only 27 percent. There are trials that are accruing with eligibility criteria that they may describe as high-risk that are beyond six months, but the data as really it's been defined in the literature highlights that truly high-risk BCR is less than six months. And the working group had a consensus on that opinion, and that was our recommendation. David Einstein: And I think an important follow-on to that is that's regardless of PET findings, right? And so, we present a couple of case studies of patients with positive PET findings who have a long doubling time, in whom the disease is in fact indolent, as you would have expected from a traditional BCR prognostic standpoint. Obviously, there are patients in whom they have fast doubling times, and even if they do not have PET findings, that doesn't make them not high-risk. Ravi Madan: And just to follow up that point, I will let you know a little bit of a free preview that my colleague Melissa Abel from the NCI will be presenting PSMA findings in the context of PSA doubling time at ASCO GU if that data is accepted. Davide Soldato: Looking forward for those data because I think that they're going to clarify a lot of the findings that we have in this specific population. And coming back to one of the points that we made before, so PET PSMA has a very high ability to discriminate also a very low burden of disease, which we currently refer to as oligometastatic biochemically recurrent prostate cancer, which is not entirely defined as an entity. But what we are seeing both in some clinical trials, which use mainly conventional imaging, but also what we're starting to see in clinical practice, is that frequently we use the metastasis-directed therapy to treat these patients. So, just a little bit of a comment on the use of this type of strategy in clinical practice and if the panel thought of including this as, for example, a stratification criteria or mandated in the design of novel clinical trials in the field of BCR? David Einstein: Yeah, I think that's an incredibly important point. You know, fundamentally, there's a lot of heterogeneity in practice where some folks are using local salvage approaches, some are using systemic therapies, in some cases surveillance may be reasonable, or some combination of these different strategies. We certainly have phase two data from multiple trials suggesting that met-directed therapy may help buy patients time off of treatment until subsequent treatments are started. And that in and of itself may be an important goal that we can come back to in discussing novel endpoints. I think what our panel acknowledged was that, in some sense, the clinical practice has gotten even farther ahead than where the data are, and this is being offered pretty routinely to patients in practice. And so, what became clear was that we, in developing clinical trials, cannot forbid investigators from doing something that would be within their usual standard of care, even if it might not be supported by the most robust data. But at minimum, it definitely should be used as a stratification factor, or in some trial designs, you can do met-directed therapy after a primary endpoint is assessed. And that offers a compromise between testing, say, the effect of a systemic therapy but also not excluding patients and investigators from doing what they would have done had they not been on a study. Ravi Madan: And I would just like to follow up your phrasing in the question of "oligometastatic prostate cancer." We have a figure in the paper and it highlights the fact that, unfortunately, that term in prostate cancer is imaging agnostic. And we've already discussed in this podcast, as well as in the paper, that imaging used to define a metastatic lesion, whether it's PSMA or conventional imaging, carries with it a different clinical weight and a different prognosis. So, we feel in the working group, that the correct term for this disease state of PSMA-positive BCR is just that: PSMA-positive BCR. We also have to realize that when we talk about oligometastatic disease, while it's imaging agnostic, it seems to be numerically based, whether it's five or three or 10 depending on the trial. But PSMA-positive BCR does not have a limit in terms of the number of lesions. And so again, we just feel that there is an important need to delineate what we're seeing in this disease state, which again is PSMA-positive BCR, and that should be differentiated frankly from oligometastatic disease defined on other imaging platforms. David Einstein: Right, and that also makes clear that patients can have polyfocal disease on PET that still is not what we would consider metastatic, but goes beyond the traditional definition of oligometastatic. So, in other words, just because someone has PET-detected disease only, that does not automatically equate with oligometastatic. Davide Soldato: Thanks so much. So, you were speaking a little bit, Dr. Einstein, about the different types of treatment that we can propose or not propose to this patient because you mentioned, for example, that in clinical practice MDT, so metastasis-directed therapy, is becoming more and more used. For these patients, we can potentially use systemic treatments, which include androgen deprivation therapy, which can be given continuously or in an intermittent fashion. And recently, we can also use novel systemic therapies, for example, enzalutamide, to treat this type of patient. So, given that the point of the consensus was really to provide consideration for novel clinical trials in this space, what was the opinion on the panel regarding the control arm? So, if we're looking at a novel therapy in the BCR space, does the control arm need to include a therapy or not? And if so, which therapy? David Einstein: Yeah, this is a super important question and one that's subject to a lot of discussion, especially in light of recent data from EMBARK. What we came to a consensus around was the fact that neither MDT nor systemic therapy should be required as a control arm on BCR trials. And we can talk about a number of reasons for that. There's also the pragmatics of what investigators might actually accrue patients to and what they would consider their standard of care, and that's important to factor in, too. I think that one of the major goals of our working group was outlining what kinds of trials we would like to see in the future and where the limitations of the current data stand. For example, EMBARK proposes a strategy of a single treatment discontinuation and resumption at a predefined threshold indefinitely. That's probably not how most people are practicing. Most folks are probably using some version of intermittent therapy as they would have before this trial, but we actually don't have any data supporting that. Moreover, we don't have data comparing different intermittent strategies to one another. We don't know what the right thresholds are, we don't know how much time we buy patients off treatment, and we don't know to what extent MDT modifies that. And so, those are all really important questions to be asking in future versions of these trials. I'd say my second point would be that a lot of drug development is happening with novel therapies that are not hormonal, trying to bring them into this space. And when you think about trying to compare one of those types of therapies to a hormonal therapy on short-term endpoints, the hormonal therapy is always going to win. Hormonal therapy is almost universally effective, it will bring down PSAs, and it will prolong, quote-unquote, "progression." The downside of that is that hormonal therapy doesn't actually modify the disease, it suppresses it, and it tends to have fairly transient effects once you remove it. And so, part of our goal was in trying to figure out some novel endpoints that would allow these novel types of therapies to be examined head-to-head against a more traditional type of hormonal therapy and have some measurement of some of the more long-term impacts. Davide Soldato: So, jumping right into the endpoints, because this is a very relevant and I think very well-constructed part of the paper that you published. Because in the past we have used some of these endpoints, for example, metastasis-free survival, as potentially a proxy for long-term outcomes. But is this the right endpoint to be using right now, especially considering that frequently this outcome is measured using conventional imaging, but we are including in these trials patients who are actually negative on conventional imaging but have a positive PSMA when they enter this type of trial? David Einstein: Yeah, there's a number of challenges with those types of endpoints. One of which is, as you say, we're changing the goalposts a little bit on how we're calling progression. We still don't exactly understand what progression on PET means, and so that's something that is challenging. That said, we're also cognizant of the fact that many times investigators are likely to get PET scans in the setting of rising PSA, and that's going to affect any endpoint that relies purely on conventional imaging. So, there's some tension there between these two different sets of goalposts. One thing that we emphasize is that not only are there some challenges in defining those, but also there're challenges in what matters to a patient. So, if a progression event occurs in the form of a single lesion on a PET scan or even a conventional image, that might be relevant for a clinical trial but might be less relevant for a patient. In other words, that's something that, in the real world, an investigator might use serial rounds of metastasis-directed therapy or intermittent therapy to treat in a way that doesn't have any clinical consequences for the patient necessarily. In other words, they're asymptomatic, it's not the equivalent of a metastatic castration-resistant disease progressing. And so, we also need to be cognizant of the fact that if we choose a single endpoint like PFS, that there's going to be many different versions of progression, some of which probably matter clinically more than others, and some of which are more salvageable by local therapies than others. Ravi Madan: So I think the working group really thoughtfully looked at the different options and underscored perhaps strengths and weaknesses, and I think that's presented as you mentioned in the paper. But I think it's also going to depend on the modality, the approach of the therapeutic intervention. In some cases if it's hormone-based, then maybe PSA is providing some early metrics, maybe metastasis-free survival is more relevant in a continuous therapy, but intermittent therapies might have a different approach. There's emerging immunotherapy strategies, radiopharmaceutical strategies, they might have some more novel strategies as well. I think we have to be open-minded here, but we also have to be very clear: we do not know what progression is on a PSMA scan. Just new lesions may not carry the clinical significance that we think, and we may not know what threshold that ultimately becomes clinically relevant is. So, I do think that there was some caution issued by the working group about using PSMA as an endpoint because we still do not have the data to understand what that modality is telling us. Again, I'm optimistic that the National Cancer Institute's prospective data set that we've been collecting, which has over 130 patients now, will provide some insights in the months and years ahead. Davide Soldato: So, just to ask the question very abruptly, what would you feel like the best endpoint for this type of trials is? I understand that is a little bit related to the type of treatments that we're going to use, whether it's intermittent, whether it's continuous, but do we have something that can encapsulate all of the discussion that we have up until this point? David Einstein: Yeah, so that's a perfect segue to the idea of novel endpoints, which we feel are very important to develop in these novel disease spaces. So, one thing that we discussed was an endpoint called treatment-free survival, which conceptually you can think of as exactly what it sounds like, but statistically you actually have to do some work to get there. And so essentially, you imagine a series of Kaplan-Meier curves overlaid: one about overall survival, one time to next therapy, one time on initial therapy. You can actually then take the area under those curves or between those curves and essentially sum it up using restricted mean survival time analysis. And that can give you a guide about the longitudinal experience of a patient: time spent on treatment versus off treatment; time spent with toxicity versus without toxicity. And importantly, each one of those time-to-event metrics can be adjusted depending on exactly what the protocol is and what is allowed or not allowed and what's prespecified as far as initiation of subsequent therapies. So, we felt that this was a really important endpoint to develop in this disease space because it can really capture that longitudinal aspect. It can really reward treatments that are effective in getting durable responses and getting patients off of therapy, because unfortunately, PFS-based endpoints generally reward more or longer systemic therapy versus shorter or no systemic therapy, and that's sort of an artificial bias in the way those endpoints are constructed. So, I think that there are challenges of course in implementing any new endpoint, and some of the things that are really critical are collecting data about toxicity and about subsequent therapies beyond what a typical trial might collect. But I think in this kind of disease space, that longitudinal aspect is critical because these are really patients who are going to be going through multiple rounds of therapy, going to be going on and off treatments, they're going to be using combinations of local and systemic therapies. And so, any one single endpoint is going to be limited, but I think that really highlights the limitations of using PFS-based endpoints in this space. Ravi Madan: I also think that in the concept of treatment-free survival lies one of the more powerful and, honestly, I was surprised by this, that it was so universally accepted, recommendations from the committee. And that was that the general approach to trials in this space should be a de-escalation of the EMBARK strategy as it's laid out with relatively continuous therapy with one pause. And so, I think again, buried in all of this highlights the need for novel endpoints like treatment-free survival. We get to the fact that these are patients who are not at near-term clinical risk from symptoms of their disease, so de-escalating therapies does not put them at risk. And if you look at, for example, lower-volume metastatic castration-sensitive prostate cancer, it's become realized that we need to de-escalate, and there are now trials being done to look at that. Historically, we know that BCR is an indolent disease process for the vast majority of patients who are not at near-term risk from clinical deterioration. So, therefore, we shouldn't wait a decade into abundant BCR trials to de-escalate. The de-escalation strategy should be from the outset. And that was something the committee really actually universally agreed on. David Einstein: And that de-escalation can really take multiple forms. That could be different strategies for intermittent therapy, different start-stop strategies. It could also mean actually intensifying in the short-term with the goal long-term de-intensification, kind of analogous to kidney cancer where we might use dual checkpoint inhibitors up front with some higher upfront toxicity but with the hope of actually long-term benefit and actually being able to come off treatment and stay in remission. Those kinds of trade-offs are the types of things that are challenging to talk about. There's not a one-size-fits-all answer for every patient. And so, that's why some of these endpoints like treatment-free survival would be really helpful in actually quantifying those trade-offs and allowing each patient to make decisions that are concordant with their own wishes. Davide Soldato: Thanks so much. That was very clear, especially on the part of de-escalation, because, as you were mentioning, I think that we are globally talking about a situation, a clinical situation, where the prognosis can be very good and patients can stay off treatment for a very long period of time without compromising long-term outcomes. And I think that well-constructed de-escalation trials, as you were mentioning and as the consensus endorsed, are really needed in this space also to limit toxicity. This brings us to the end of this episode. So, I would like to thank again Dr. Einstein and Dr. Madan for joining us today. David Einstein: We really appreciate the time and the thought, and I think that even starting these types of discussions is critical. Even just recognizing that this is a unique space is the beginning of the conversation. Ravi Madan: Yeah, and I want to thank JCO for giving us this forum and the opportunity to publish these results and all the expert prostate cancer investigators who were part of this committee. We produced some good thoughts for the future. Davide Soldato: We appreciate you sharing more on your JCO article titled, "National Cancer Institute's Working Group on Biochemically Recurrent Prostate Cancer: Clinical Trial Design Considerations." If you enjoy our show, please leave us a rating and review and be sure to come back for another episode. You can find all ASCO shows at asco.org/podcasts. The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinion of ASCO. 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In this podcast , the Uromigos discuss the upcoming ASCO GU conference. They delve into the latest research findings, including phase 3 trials, combination therapies, and the significance of biomarkers in treatment. The conversation highlights the importance of belzutifan in kidney cancer and explores the evolving landscape of prostate and bladder cancer treatments. The hosts also share their predictions and insights on how these developments may impact clinical practice.

JCO PO author Dr. Timothy Showalter at Artera and University of Virginia shares insights into his JCO PO article, “Digital Pathology–Based Multimodal Artificial Intelligence Scores and Outcomes in a Randomized Phase III Trial in Men With Nonmetastatic Castration-Resistant Prostate Cancer” . Host Dr. Rafeh Naqash and Dr. Showalter discuss how multimodal AI as a prognostic marker in nonmetastatic castration-resistant prostate cancer may serve as a predictive biomarker with high-risk patients deriving the greatest benefit from treatment with apalutamide. TRANSCRIPT  Dr. Rafeh Naqash: Hello and welcome to JCO Precision Oncology Conversations where we'll bring you engaging conversations with authors of clinically relevant and highly significant JCO PO articles. I'm your host, Dr. Rafeh Naqash, podcast Editor for JCO Precision Oncology and assistant professor at the OU Health Stephenson Cancer Center at the University of Oklahoma. Today, we are excited to be joined by Dr. Timothy Showalter, Chief Medical Officer at Artera and professor of Radiation Oncology at the University of Virginia and author of the JCO Precision Oncology article entitled, “Digital Pathology Based Multimodal Artificial Intelligence Scores and Outcomes in a Randomized Phase 3 Trial in Men with Non-Metastatic Castration Resistant Prostate Cancer.” At the time of this recording, our guest's disclosures will be linked in the transcript. Dr. Showalter, it's a pleasure to have you here today. Dr. Timothy Showalter: It's a pleasure to be here. Thanks for having me. Dr. Rafeh Naqash: I think this is going to be a very interesting discussion, not just from a biomarker perspective, but also in terms of how technologies have evolved and how we are trying to stratify patients, trying to escalate or deescalate treatments based on biomarkers. And this article is a good example of that. One of the things I do want to highlight as part of this article is that Dr. Felix Feng is the first author for this article. Unfortunately, Dr. Felix Feng passed away in December of 2024. He was a luminary in this field of prostate cancer research. He was also the Chair of the NRG GU Committee as well as Board of Directors for RTOG Foundation and has mentored a lot of individuals from what I have heard. I didn't know Dr. Feng but heard a lot about him from my GU colleagues. It's a huge loss for the community, but it was an interesting surprise for me when I saw his name on this article as I was reviewing it. Could you briefly talk about Dr. Feng for a minute and how you knew him and how he's been an asset to the field? Dr. Timothy Showalter: Yeah. I'm always happy to talk about Felix whenever there's an opportunity. You know, I was fortunate to know Felix Feng for about 20 years as we met during our residency programs through a career development workshop that we both attended and stayed close ever since. And you know, he's someone who made an impact on hundreds of lives of cancer researchers and other radiation oncologists and physicians in addition to the cancer patients he helped, either through direct clinical care or through his innovation. For this project in particular, I first became involved soon after Felix had co-founded Artera, which is, you know the company that developed this. And because Felix was such a prolific researcher, he was actually involved in this and this research project from all different angles, both from the multimodal digital pathology tool to the trial itself and being part of moving the field forward in that way. It's really great to be able to sort of celebrate a great example of Felix's legacy, which is team science, and really moving the field forward in terms of translational projects based on clinical trials. So, it's a great opportunity to highlight some of his work and I'm really happy to talk about it with you. Dr. Rafeh Naqash: Thanks, Tim. Definitely a huge loss for the scientific community. And I did see a while back that there was an international symposium organized, showcasing his work for him to talk about his journey last year where more than 200, 250 people from around the globe actually attended that. That speaks volumes to the kind of impact he's had as an individual and impact he's had on the scientific side of things as well. Dr. Timothy Showalter: Yes. And we just had the second annual Feng Symposium the day before ASCO GU this year with, again, a great turnout and some great science highlighted, as well as a real focus on mentorship and team science and collaboration. Dr. Rafeh Naqash: Thank you so much for telling us all about that. Now going to what you guys published in JCO Precision Oncology, which is this article on using a biomarker approach to stratify non-metastatic prostate cancer using this artificial intelligence based H&E score. Could you tell us the background for what started off this project? And I see there is a clinical trial data set that you guys have used, but there's probably some background to how this score or how this technology came into being. So, could you superficially give us an idea of how that started? Dr. Timothy Showalter: Sure. So, the multimodal AI score was first published in a peer reviewed journal back in 2022 and the test was originally developed through a collaboration with the Radiation Therapy Oncology Group or Energy Oncology Prostate Cancer Research Team. The original publication describes development and validation of a risk stratification tool designed to predict distant metastasis and prostate cancer specific mortality for men with localized prostate cancer. And the first validation was in men who were treated with definitive radiation therapy. There have been subsequent publications in that context and there's a set of algorithms that have been validated in localized prostate cancer and there's a test that's listed on NCCN guidelines based on that technology. The genesis for this paper was really looking at extending that risk stratification tool that was developed in localized prostate cancer to see if it could one, validate in a non-metastatic castrate refractory prostate cancer population for patients enrolled on the SPARTAN trial. And two, whether there was a potential role for the test output in terms of predicting benefit from apalutamide for patients with non-metastatic prostate cancer. For patients who are enrolled on the SPARTAN study, almost 40% of them had H&E stain biopsy slide material available and were eligible to be included in this study. Dr. Rafeh Naqash: Going a step back to how prostate cancer, perhaps on the diagnostic side using the pathology images is different as you guys have Gleason scoring, which to the best of my knowledge is not necessarily something that most other tumor types use. Maybe Ki-67 is somewhat of a comparison in some of the neuroendocrine cancers where high Ki-67 correlates with aggressive biology for prognosis. And similarly high Gleason scores, as we know for some of the trainees, correlates with poor prognosis. So, was the idea behind this based on trying to stratify or sub-stratify Gleason scoring further, where you may not necessarily know what to do with the intermediate high Gleason score individual tumor tissues? Dr. Timothy Showalter: Well, yeah. I mean, Gleason score is a really powerful risk stratification tool. As you know, our clinical risk groupings are really anchored to Gleason scores as an important driver for that. And while that's a powerful tool, I think, you know, some of the original recognition for applying computer vision AI into this context is that there are likely many other features located in the morphology that can be used to build a prognostic model. Going back to the genesis of the discovery project for the multimodal AI model, I think Felix Feng would have described it as doing with digital pathology and computer vision AI what can otherwise be done with gene expression testing. You know, he would have approached it from a genomic perspective. That's what the idea was. So, it's along the line of what you're saying, which is to think about assigning a stronger Gleason score. But I think really more broadly, the motivation was to come up with an advanced complementary risk stratification tool that can be used in conjunction with clinical risk factors to help make better therapy recommendations potentially. So that was the motivation behind it. Dr. Rafeh Naqash: Sure. And one of the, I think, other important teaching points we try to think about, trainees of course, who are listening to this podcast, is trying to differentiate between prognostic and predictive scores. So, highlighting the results that you guys show in relation to the MMAI score, the digital pathology score, and outcomes as far as survival as well as outcomes in general, could you try to help the listeners understand the difference between the prognostic aspect of this test and the predictive aspect of this test? Dr. Timothy Showalter: So let me recap for the listeners what we found in the study and how it kind of fits into the prognostic and the predictive insights. So, one, you know, as I mentioned before, this is ultimately a model that was developed and validated for localized prostate cancer for risk stratification. So, first, the team looked at whether that same tool developed in localized prostate cancer serves as a prognostic tool in non-metastatic castrate-refractory prostate cancer. So, we applied the tool as it was previously developed and identified that about 2/3 of patients on the SPARTAN trial that had specimens available for analysis qualified as high risk and 1/3 of patients as either intermediate or low risk, which we called in the paper ‘non-high risk'. And we're able to show that the multimodal AI score, which ranges from 0 to 1, and risk group, was associated with metastasis free survival time to second progression or PFS 2 and overall survival. And so that shows that it performs as a prognostic tool in this setting. And this paper was the first validation of this tool in non-metastatic castrate-refractory prostate cancer. So, what that means to trainees is basically it helps you understand how aggressive that cancer is or better stratify the risk of progression over time. So that's the prognostic performance. Dr. Rafeh Naqash: Thank you for trying to explain that. It's always useful to get an example and understand the difference between prognostic and predictive. Now again, going back to the technology, which obviously is way more complicated than the four letter word MMAI, I per se haven't necessarily done research in this space, but I've collaborated with some individuals who've done digital pathology assessments, and one of the projects we worked on was TIL estimation and immune checkpoint related adverse events using some correlation and something that one of my collaborators had sent to me when we were working on this project as part of this H&E slide digitalization, you need color deconvolution, you need segmentation cell profiling. Superficially, is that something that was done as part of development of this MMAI score as well? Dr. Timothy Showalter You need a ground truth, right? So, you need to train your model to predict whatever the outcome is. You know, if you're designing an AI algorithm for Ki-67 or something I think you mentioned before, you would need to have a set of Ki-67 scores and train your models to create those scores. In this case, the clinical annotation for how we develop the multimodal AI algorithm is the clinical endpoints. So going back to how this tool was developed, the computer vision AI model is interpreting a set of features on the scan and what it's trying to do is identify high risk features and make a map that would ultimately predict clinical outcomes. So, it's a little bit different than the many digital pathology algorithms where the AI is being trained to predict a particular morphological finding. In this case, the ground truth that the model is trained to predict is the clinical outcome. Dr. Rafeh Naqash: Sure. And from what you explained earlier, obviously, tumors that had a high MMAI score were the ones that were benefiting the most from the ADT plus the applausive. Is this specific for this androgen receptor inhibitor or is it interchangeable with other inhibitors that are currently approved? Dr. Timothy Showalter: That's a great question and we don't know yet. So, as you're alluding to, we did find that the MMAI risk score was predictive for benefit from apalutamide and so it met the statistical definition of having a significant interaction p value so we can call it a predictive performance. And so far, we've only looked in this population for apalutamide. I think you're raising a really interesting point, which is the next question is, is this generalizable to other androgen receptor inhibitors? There will be future research looking at that, but I think it's too early to say. Just for summary, I think I mentioned before, there are about 40% of patients enrolled on the SPARTAN study had specimens available for inclusion in this analysis. So, the SPARTAN study did show in the entire clinical trial set that patients with non-metastatic castrate-refractory prostate cancer benefited from apalutamide. The current study did show that there seems to be a larger magnitude of benefit for those patients who are multimodal AI high risk scores. And I think that's very interesting research and suggests that there's some interaction there. But I certainly would want to emphasize that we have not shown that patients with intermediate or low risk don't benefit from apalutamide. I think we can say that the original study showed that that trial showed a benefit and that we've got this interesting story with multimodal AI as well. Dr. Rafeh Naqash: Sure. And I think from a similar comparison, ctDNA where ctDNA shows prognostic aspects, I treat people with lung cancer especially, and if you're ctDNA positive at a 3 to 4-month period, likely chances of you having a shorter disease-free interval is higher. Same thing I think for colorectal cancers. And now there are studies that are using ctDNA as an integral biomarker to stratify patients positive/negative and then decide on escalation/de-escalation of treatment. So, using a similar approach, is there something that is being done in the context of the H&E based stratification to de-intensify or intensify treatments based on this approach? Dr. Timothy Showalter: You're hitting right on the point in the most promising direction. You know, as we pointed out in the manuscript, one of the most exciting areas as a next step for this is to use a tool like this for stratification for prospective trials. The multimodal AI test is not being used currently in clinical trials of non-metastatic castrate-refractory prostate cancer, which is a disease setting for this paper. There are other trials that are in development or currently accruing where multimodal AI stratification approach is being taken, where you see among the high-risk scores, at least in the postoperative setting for a clinical trial that's open right now, high risk score patients are being randomized to basically a treatment intensification question. And then the multimodal AI low risk patients are being randomized to a de-intensification experimental arm where less androgen deprivation therapy is being given. So, I think it's a really promising area to see, and I think what has been shown is that this tool has been validated really across the disease continuum. And so, I think there are opportunities to do that in multiple clinical scenarios. Dr. Rafeh Naqash: Then moving on to the technological advancements, very fascinating how we've kind of evolved over the last 10 years perhaps, from DNA based biomarkers to RNA expression and now H&E. And when you look at cost savings, if you were to think of H&E as a simpler, easier methodology, perhaps, with the limitations that centers need to digitalize their slides, probably will have more cost savings. But in your experience, as you've tried to navigate this H&E aspect of trying to either develop the model or validate the model, what are some of the logistics that you've experienced can be a challenge? As we evolve in this biomarker space, how can centers try to tackle those challenges early on in terms of digitalizing data, whether it's simple data or slides for that matter? Dr. Timothy Showalter: I think there's two main areas to cover. One, I think that the push towards digitalization is going to be, I think, really driven by increasing availability and access to augmentative technologies like this multimodal AI technology where it's really adding some sort of a clinical insight beyond what is going to be generated through routine human diagnostic pathology. I think that when you can get these sorts of algorithms for patient care and have them so readily accessible with a fast turnaround time, I think that's really going to drive the field forward. Right now, in the United States, the latest data I've seen is that less than 10% of pathology labs have gone digital. So, we're still at an early stage in that. I hope that this test and similar ones are part of that push to go more digital. The other, I think, more interesting challenge that's a technical challenge but isn't about necessarily how you collect the data, but it certainly creates data volume challenges, is how do you deal with image robustness and sort of translating these tools into routine real-world settings. And as you can imagine, there's a lot of variation for staining protocols, intensity scanner variations, all these things that can affect the reliability of your test. And at least for this research group that I'm a part of that has developed this multimodal AI tool can tell you that the development is sophisticated, but very data and energy intensive in terms of how to deal with making a tool that can be consistent across a whole range of image parameters. And so that presents its own challenges for dealing with a large amount of compute time and AI cycles to make robust algorithms like that. And practically speaking, I think moving into other diseases and making this widely available, the size of data required and the amount of cloud compute time will be a real challenge. Dr. Rafeh Naqash: Thank you for summarizing. I can say that definitely, you know, this is maybe a small step in prostate cancer biomarker research, but perhaps a big step in the overall landscape of biomarker research in general. So definitely very interesting. Now, moving on to the next part of the discussion is more about you as a researcher, as an individual, your career path, if you can summarize that for us. And more interestingly, this intersection between being part of industry as well as academia for perhaps some of the listeners, trainees who might be thinking about what path they want to choose. Dr. Timothy Showalter: Sure. So, as you may know, I'm a professor at the University of Virginia and I climbed the academic ladder and had a full research grant program and thought I'd be in academia forever. And my story is that along the way, I kind of by accident ended up founding a medical device company that was called Advaray and that was related to NCI SBIR funding. And I found myself as a company founder and ultimately in that process, I started to learn about the opportunity to make an impact by being an innovator within the industry space. And that was really the starting point for me. About four years ago, soon after Felix Feng co-founded Artera, he called me and told me that he needed me to join the company. For those who were lucky to know Felix well, at that very moment, it was inevitable that I was going to join Artera and be a part of this. He was just so persuasive. So, I will say, you know, from my experience of being sort of in between the academic and industry area, it's been a really great opportunity for me to enter a space where there's another way of making an impact within cancer care. I've gotten to work with top notch collaborators, work on great science, and be part of a team that's growing a company that can make technology like this available. Dr. Rafeh Naqash: Thank you so much, Tim, for sharing some of those thoughts and insights. We really appreciate you discussing this very interesting work with us and also appreciate you submitting this to JCO Precision Oncology and hopefully we'll see more of this as this space evolves and maybe perhaps bigger more better validation studies in the context of this test. Thank you for listening to JCO Precision Oncology Conversations. Don't forget to give us a rating or review and be sure to subscribe so you never miss an episode. You can find all ASCO shows at asco.org/podcast.   The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.  

On the inaugural episode of ASCO Education: By the Book, Dr. Nathan Pennell and Dr. Don Dizon share reflections on the evolution of the ASCO Educational Book, its global reach, and the role of its new companion podcast to further shine a spotlight on the issues shaping the future of modern oncology. TRANSCRIPT Dr. Nathan Pennell: Hello, I'm Dr. Nate Pennell, welcoming you to the first episode of our new podcast, ASCO Education: By the Book. The podcast will feature engaging discussions between editors and authors from the ASCO Educational Book. Each month, you'll hear nuanced views on key topics in oncology featured in Education Sessions at ASCO meetings, as well as some deep dives on the advances shaping modern oncology. Although I am honored to serve as the editor-in-chief (EIC) of the ASCO Educational Book, in my day job, I am the co-director of the Cleveland Clinic Lung Cancer Program and vice chair for clinical research for the Taussig Cancer Center here in Cleveland. I'm delighted to kick off our new podcast with a discussion featuring the Ed Book's previous editor-in-chief. Dr. Don Dizon is a professor of medicine and surgery at Brown University and works as a medical oncologist specializing in breast and pelvic malignancies at Lifespan Cancer Institute in Rhode Island. Dr. Dizon also serves as the vice chair for membership and accrual at the SWOG Cancer Research Network. Don, it's great to have you here for our first episode of ASCO Education: By the Book. Dr. Don Dizon: Really nice to be here and to see you again, my friend. Dr. Nathan Pennell: This was the first thing I thought of when we were kicking off a podcast that I thought we would set the stage for our hopefully many, many listeners to learn a little bit about what the Ed Book used to be like, how it has evolved over the last 14 years or so since we both started here and where it's going. You started as editor-in-chief in 2012, is that right? Dr. Don Dizon: Oh, boy. I believe that is correct, yes. I did two 5-year stints as EIC of the Educational Book, so that sounds about right. Although you're aging me very clearly on this podcast. Dr. Nathan Pennell: I had to go back in my emails to see if I could figure out when we started on this because we've been working on it for some time. Start out a little bit by telling me what do you remember about the Ed Book from back in the day when you were applying to be editor-in-chief and thinking about the Ed Book. What was it like at that time? Dr. Don Dizon: You know, it's so interesting to think about it.  Ten years ago, we were both in a very different place in our careers, and I remember when the Ed Book position came up, I had been writing a column for ASCO. I had done some editorial activities with other journals for sure, but what always struck me was it was very unclear how one was chosen to be a part of the education program at ASCO. And then it was very unclear how those faculty were then selected to write a paper for the Educational Book. And it was back in the day when the Educational Book was completely printed. So, there was this book that was cherished among American fellows in oncology. And it was one that, when I was newly attending, and certainly two or three years before the editor's position came up, it was one that I referenced all the time. So, it was a known commodity for many of us. And there was a certain sense of selectivity about who was invited to write in it. And it wasn't terribly transparent either. So, when the opportunity to apply for editor-in-chief of the Educational Book came up, I had already been doing so much work for ASCO. I had been on the planning committees and served in many roles across the organization, and editing was something I found I enjoyed in other work. So, I decided to put my name in the ring with the intention of sort of bringing the book forward, getting it indexed, for example, so that there was this credit that was more than just societal credit at ASCO. This ended up being something that was referenced and acknowledged as an important paper through PubMed indexing. And then also to provide it as a space where we could be more transparent about who was being invited and broadening the tent as to who could participate as an author in the Ed Book. Dr. Nathan Pennell: It's going to be surprising to many of our younger listeners to learn that the Educational Book used to be just this giant, almost like a brick. I mean, it was this huge tome of articles from the Education Sessions that you got when you got your meeting abstracts book at the annual meeting. And you can always see people on the plane on the way out of Chicago with their giant books. Dr. Don Dizon: Yes. Dr. Nathan Pennell: That added lots of additional weight to the plane, I'm sure, on the way out. Dr. Don Dizon: And it was not uncommon for us to be sitting at an airport, and people would be reading those books with highlighters. Dr. Nathan Pennell: I fondly remember being a fellow and coming up and the Ed Book was always really important to me, so I was excited. We'll also let the listeners in on that. I also applied to be the original editor-in-chief of the Ed Book back in 2012, although I was very junior and did not have any real editorial experience. I think I may have been section editor for The Oncologist at that point. And I had spoken to Dr. Ramaswamy Govindan at WashU who had been the previous editor-in-chief about applying and he was like, “Oh yeah. You should absolutely try that out.” And then when Dr. Dizon was chosen, I was like, “Oh, well. I guess I didn't get it.” And then out of the blue I got a call asking me to join as the associate editor, which I was really always very thankful for that opportunity. Dr. Don Dizon: Well, it was a highly fruitful collaboration, I think, between you and I when we first started. I do remember taking on the reins and sort of saying, “You know, this is our vision of what we want to do.” But then just working with the authors, which we did, about how to construct their papers and what we were looking for, all of that is something I look back really fondly on. Dr. Nathan Pennell: I think it was interesting too because neither one of us had really a lot of transparency into how things worked when we started. We kind of made it up a little bit as we went along. We wanted to get all of the faculty, or at least as many of them as possible contributing to these. And we would go to the ASCO Education Committee meeting and kind of talk about the Ed Book, and we were thinking about, you know, how could we get people to submit. So, at the time it wasn't PubMed indexed. Most people, I think, submitted individual manuscripts just from their talk, which could be anywhere from full length review articles to very brief manuscripts. Dr. Don Dizon: Sometimes it was their slides with like a couple of comments on it. Dr. Nathan Pennell: And some of them were almost like a summary of the talk. Yeah, exactly. And so sort of making that a little more uniform. There was originally an honorarium attached, which went away, but I think PubMed indexing was probably the biggest incentive for people to join. I remember that was one of the first things you really wanted to get. Dr. Don Dizon Yeah. And, you know, it was fortuitous. I'd like to take all the credit for it, but ASCO was very forward thinking with Dr. Ramaswamy and the conversations about going to PubMed with this had preceded my coming in. We knew what we needed to do to get this acknowledged, which was really strengthening the peer review so that these papers could meet the bar to get on PubMed. But you know, within the first, what, two or three years, Nate, of us doing this, we were able to get this accepted. And now it is. If you look at what PubMed did for us, it not only increased the potential of who was going to access it, but for, I think the oncology community, it allowed people access to papers by key opinion leaders that was not blocked by a paywall. And I thought that was just super important at the time. Social media was something, but it wasn't what it is now. But anybody could access these manuscripts and it's still the case today. Dr. Nathan Pennell: I think it's hard to overstate how important that was. People don't realize this, but the Ed Book is really widely accessed, especially outside the US as well. And a lot of people who can't attend the meeting to get the print, well, the once print, book could actually get access to essentially the education session from the annual meeting without having to fly all the way to the US to attend. Now, you know, we have much better virtual meeting offerings now and whatnot. But at the time it was pretty revolutionary to be able to do that. Dr. Don Dizon: Yeah, and you know, it's so interesting when I think back to, you know, this sort of evolution to a fully online publication of the Ed Book. It was really some requests from international participants of the annual meeting who really wanted to continue to see this in print. At that time, it was important to recognize that access to information was not uniform across the world. And people really wanted that print edition, maybe not for themselves, but so that access in more rural areas or where access in the broadband networks were not established that they still could access the book. I think things have changed now. We were able, I think, in your tenure, to see it fully go online. But even I just remember that being a concern as we went forward. Dr. Nathan Pennell: Yeah, we continued with the print book that was available if people asked for it, but apparently few enough people asked for it that it moved fully online. One of the major advantages of being fully online now is of course, it does allow us to publish kind of in real time as the manuscripts come out in the months leading up to the meeting, which has been, I think, a huge boon because it can build momentum for the Education Sessions coming in. People, you know, really look forward to it. Dr. Don Dizon: Yeah, that was actually a concern, you know, when we were phasing out Ed Book and going to this continuous publication model where authors actually had the ability to sort of revise their manuscript and that would be automatically uploaded. You had a static manuscript that was fully printed, and it was no longer an accurate one. And we did have the ability to fix it. And it just goes to show exactly what you're saying. This idea that these are living papers was really an important thing that ASCO embraced quite early, I think. Dr. Nathan Pennell: And with the onset of PubMed indexing, the participation from faculty skyrocketed and almost within a couple of years was up to the vast majority of sessions and faculty participating. Now I think people really understand that this is part of the whole process. But at the time I remember writing out on my slides in all caps, “THIS IS AN EXPECTATION.” And that's about the best word I could give because I asked if we could make people do it, and they were like, no, you can't make people do it. Dr. Don Dizon: So right.  Actually, I don't think people are aware of the work on the back end every year when I was on as EIC, Nate and myself, and then subsequently Dr. Hope Rugo would have these informational sessions with the education faculty and we would tout the Ed Book, tout the expectation, tout it was PubMed indexed and tout multidisciplinary participation. So, we were not seeing four manuscripts reflecting one session. You know, this encouragement to really embrace multidisciplinary care was something that very early on we introduced and really encouraged people not to submit perspective manuscripts, but to really get them in and then harmonize the paper so that it felt like it was, you know, one voice. Dr. Nathan Pennell: I consider that after PubMed indexing, the next major change to the Ed Book, that really made it a better product and that was moving from, you know, just these short individual single author manuscripts to single session combined manuscript that had multiple perspectives and topics, really much more comprehensive review articles. And I don't even remember what the impetus was for that, but it was really a success. Dr. Don Dizon: Yeah, I mean, I think in the beginning it was more of a challenge, I think, because people were really not given guidance on what these papers were supposed to look like. So, we were seeing individual manuscripts come forward. Looking back, it really foreshadowed the importance of multidisciplinary management. But at the time, it was really more about ensuring that people were leaving the session with a singular message of what to do when you're in clinic again. And the goal was to have the manuscripts reflect that sort of consensus view of a topic that was coming in. There were certain things that people still argued would not fit in a multidisciplinary manuscript. You know, if you have someone who's writing and whose entire talk was on the pathology of thyroid cancer. Another topic was on survivorship after thyroid cancer. It was hard to sort of get those two to interact and cover what was being covered. So, we were still getting that. But you're right, at the end of my tenure and into yours, there were far fewer of those individual manuscripts. Dr. Nathan Pennell: And I think it's even made it easier to write because now, you know, you just have to write a section of a manuscript and not put together an entire review. So, it has helped with getting people on board. Dr. Don Dizon: Well, the other thing I thought was really interesting about the process is when you're invited to do an Education Session at ASCO, you're either invited as a faculty speaker or as the chair of the session. And the responsibility of the chair is to ensure that it flows well and that the talks are succinct based on what the agenda or the objectives were as defined by the education committee for that specific group. But that was it. So really being named “Chair” was sort of an honor, an honorific. It really didn't come with responsibility. So, we use the Ed Book as a way to say, “As chair of the session, it is your responsibility to ensure A, a manuscript comes to me, but B, that the content of that paper harmonizes and is accurate.” And it was very rare, but Nate, I think we got dragged into a couple of times where the accuracy of the manuscript was really called into question by the chair. And those were always very, very tricky discussions because everyone that gets invited to ASCO is a recognized leader in their field. Some of us, especially, I would probably say, dating back 10 years from today, the data behind Standards of Care were not necessarily evidence-based. So, there were a lot of opinion-based therapies. You know, maybe not so much in the medical side, but certainly some of it. But when you went to, you know, surgical treatments and maybe even radiotherapy treatments, it was really based on, “My experience at my center is this and this is why I do what I do.” But those kinds of things ended up being some of the more challenging things to handle as an editor. Dr. Nathan Pennell: And those are the– I'll use “fun” in a broad sense. You know, every once in a while, you get an article where it really does take a lot of hands-on work from the editor to work with the author to try to revise it and make it a suitable academic manuscript. But you know what? I can't think, at least in recent years, of any manuscripts that we turned down. They just sometimes needed a little TLC. Dr. Don Dizon: Yeah. And I think the other important thing it reminds me of is how great it was that I wasn't doing this by myself. Because it was so great to be able to reach out to you and say, “Can you give me your take on this paper?” Or, “Can you help me just join a conference call with the authors to make sure that we're on the same page?” And then on the rare example where we were going to reject a paper, it was really important that we, as the editorial team, and I include our ASCO shepherder, through the whole process. We had to all agree that this was not salvageable. Fortunately, it happened very rarely. But I've got to say, not doing this job alone was one of the more important facets of being the EIC of ASCO's Educational Book. Dr. Nathan Pennell: Well, it's nice to hear you say that. I definitely felt that this was a partnership, you know, it was a labor of love. So, I want to go to what I consider sort of the third major pillar of the changes to the Ed Book during your tenure, and that was the introduction of a whole new kind of manuscript. So up to, I don't know, maybe seven or eight years ago, all the articles were authored just by people who were presenting at the Annual Meeting. And then you had an idea to introduce invited manuscripts. So take me through that. Dr. Don Dizon: Yeah, well, you know, again, it went to this sort of, what can people who are being asked to sort of lead ASCO for that year, what can they demonstrate as sort of a more tangible contribution to the Society and to oncology in general? And I think that was the impetus to use the Ed Book for everyone who was in a leadership position to make their mark. That said, I was here, and I was either president of the society or I was Education Program Chair or Scientific Program Chair, and they got to select an article type that was not being covered in the annual meeting and suggest the authors and work with those authors to construct a manuscript. Never did any one of those folks suggest themselves, which I thought was fascinating. They didn't say, “I want to be the one to write this piece,” because this was never meant to be a presidential speech or a commemorative speech or opportunity for them as leaders. But we wanted to ensure that whatever passion they had within oncology was represented in the book. And again, it was this sort of sense of, I want everyone to look at the Ed Book and see themselves in it and see what they contributed. And that was really important for those who were really shepherding each Annual Meeting each year for ASCO that they had the opportunity to do that. And I was really pleased that leadership really took to that idea and were very excited about bringing ideas and also author groups into the Educational Book who would not have had the opportunity otherwise. I thought that was just really nice. It was about inclusiveness and just making sure that people had the opportunity to say, “If you want to participate, we want you to participate.” Dr. Nathan Pennell: Yeah, I agree. I think the ASCO leadership jumped on this and continues to still really appreciate the opportunity to be able to kind of invite someone on a topic that's meaningful to them. I think we've tried to work in things that incorporate the presidential theme each year in our invited manuscript, so it really allows them to put kind of a stamp on the flavor of each edition. And the numbers reflect that these tend to be among our more highly read articles as well. Dr. Don Dizon: You know, looking back on what we did together, that was something I'm really, really quite proud of, that we were able to sort of help the Educational Book evolve that way. Dr. Nathan Pennell: I agree. You brought up briefly a few minutes ago about social media and its role over time. I think when we started in 2012, I had just joined Twitter now X in 2011, and I think we were both sort of early adopters in the social media. Do you feel like social media has had a role in the growth of the Ed Book or is this something that you think we can develop further? Dr. Don Dizon: When we were doing Ed Book together, professional social media was actually a quite identified space. You know, we were all on the same platform. We analyzed what the outcomes were on that platform and our communities gathered on that platform. So, it was a really good place to highlight what we were publishing, especially as we went to continuous publishing.  I don't remember if it was you or me, but we even started asking our authors for a tweet and those tweets needed work. It was you. It was you or I would actually lay in these tweets to say, “Yeah, we need to just, you know, work on this.” But I think it's harder today. There's no one preferred platform. Alternate platforms are still evolving. So, I think there are opportunities there. The question is: Is that opportunity meaningful enough for the Ed Book to demonstrate its return on an investment, for example? What I always thought about social media, and it's still true today, is that it will get eyes on whatever you're looking at far beyond who you intended to see it. So, you know, your tweets regarding a phase 3 clinical trial in lung cancer, which were so informative, were reaching me, who was not a lung oncologist who doesn't even see lung cancer and getting me more interested in finding that article and more and more pointing to the Educational Book content that speaks to that piece, you know. And I think coupling an impression of the data, associating that with something that is freely accessed is, I think, a golden opportunity not only for our colleagues, but also for anyone who's interested in a topic. Whether you are diagnosed with that cancer or you are taking care of someone with that cancer, or you heard about that cancer, there are people who would like to see information that is relevant and embedded and delivered by people who know what they're talking about. And I think our voices on social media are important because of it. And I think that's where the contribution is. So, if we had to see what the metric was for any social media efforts, it has to be more of the click rates, not just by ASCO members, but the click rates across societies and across countries. Dr. Nathan Pennell: Yeah, social media is, I mean, obviously evolving quite a bit in the last couple of years. But I do know that in terms the alt metrics for the track access through social media and online, the ones that are shared online by the authors, by the Ed Book team, do seem to get more attention. I think a lot of people don't like to just sit with a print journal anymore or an email table of contents for specific journals. People find these articles that are meaningful to them through their network and oftentimes that is online on social media. Dr. Don Dizon: Yes, 100%. And you know what I think we should encourage people to do is look at the source. And if the Ed Book becomes a source of information, I think that will be a plus to the conversations in our world. We're still dealing with a place where, depending on who sponsored the trial, whether it was an industry-sponsored trial, whether it was NCI sponsored or sponsored by the National Institutes of Health, for example, access to the primary data sets may or may not be available across the world, but the Ed Book is. And if the Ed Book can summarize that data and use terms and words that are accessible no matter what your grade level of education is. If we can explain the graphs and the figures in a way that people can actually easily more understand it. If there's a way that we structure our conversations in the Ed Book so that the plethora of inclusion/exclusion criteria are summarized and simplified, then I think we can achieve a place where good information becomes more accessible, and we can point to a summary of the source data in places where the source is not available. Dr. Nathan Pennell: One of the other things that I continue to be surprised at how popular these podcasts are. And that gives you an opportunity pretty much the opposite. Instead of sort of a nugget that directs you to the source material, you've got a more in-depth discussion of the manuscript. And so, I'm delighted that we have our own podcast. For many years, the Ed Book would sort of do a sort of a “Weird Al takeover” of the ASCO Daily News Podcast for a couple of episodes around the Annual Meeting, and I think those were always really popular enough that we were able to argue that we deserved our own podcast. And I'm really looking forward to having these in-depth discussions with authors. Dr. Don Dizon: It's an amazing evolution of where the Ed Book has gone, right? We took it from print only, societally only, to something that is now accessed worldwide via PubMed. We took it from book to fully online print. And now I think making the content live is a natural next step. So, I applaud you for doing the podcast and giving people an opportunity actually to discuss what their article discusses. And if there's a controversial point, giving them the freedom and the opportunity to sort of give more nuanced views on what may not be something that there's 100% consensus over. Dr. Nathan Pennell: Yes. Well, I hope other people enjoy these as well. Just want to highlight a few of the things that have happened just in the couple years since you stepped down as editor-in-chief. One of them, and I don't know if you noticed, but last year we started adding manuscripts from the ASCO thematic meetings, so ASCO GI and ASCO GU, something we had certainly talked about in the past, but had lacked bandwidth to really do. And they seem to be pretty widely accessed. Dr. Don Dizon: That's fantastic. Yes, I do remember talking about the coverage of the thematic meetings and you're right, this takes a long time to sort of concentrate on the Annual Meeting. It may seem like everything happens in the span of like eight weeks. Dr. Nathan Pennell: It does feel like that sometimes. Dr. Don Dizon: Right? But this is actually something that starts a year before, once the education program is set. We're in the room when they set it. But then it's really chasing down manuscripts and then making sure that they're peer reviewed because the peer review is still really important, and then making sure that any revisions are made before it's finalized and goes to press. That is a many months process. So, when we're trying to introduce, “Oh, we should also do ASCO GU or-,” the question was, how do you want to do that given this very, very involved process going forward? So, I'm glad you were able to figure it out. Dr. Nathan Pennell: Well, it's challenging. I don't think people realize quite the compressed timeline for these. You know, the Education Session and authors and invited faculty are picked in the fall, and then basically you have to start turning in your manuscripts in February, March of the following year. And so, it's a really tight turnaround for this. When we talk about the ASCO thematic meetings, it's an even tighter window. Dr. Don Dizon: Right, exactly. Dr. Nathan Pennell: And so, it's challenging to get that moving, but I was really, really proud that we were able to pull that off. Dr. Don Dizon: Well, congratulations again. And I think that is a necessary step, because so much of what's going on in the various disease management sites is only covered cursorily through the Annual Meeting itself. I mean, there's just so much science breaking at any one time that I think if we want to comprehensively catalog the Year in Review in oncology, it kind of behooves us to do that. Dr. Nathan Pennell: Some other things that are coming up because we now have manuscripts that are going to be coming in year-round, and just to kind of make it easier on the editorial staff, we're going to be forming an editorial board. And in addition to our pool of reviewers who get ASCO points, please feel free to go online to the ASCO volunteer portal and sign up if you are interested in participating. So, moving forward, I'm really excited to see where things are going to go. Dr. Don Dizon: Well, that's great. That's great. And I do remember talking about whether or not we needed to have an editorial board. At least when I was there, having this carried by three people was always better than having it carried by one person. And I think as you expand the potential for submissions, it will be very helpful to have that input for sure. And then it gives another opportunity for more members to get involved in ASCO as well. Dr. Nathan Pennell: Absolutely. People want involvement, and so happy to provide that. Dr. Don Dizon: Yes. Dr. Nathan Pennell: Is there anything we didn't cover that you would like to mention before we wrap up? Dr. Don Dizon: Well, I will say this, that ASCO and through its publications not only has had this real emphasis on multidisciplinary management of cancers, especially where it was relevant, but it also always had a stand to ensure representation was front and center and who wrote for us. And I think every president, every chair that I've worked with naturally embraced that idea of representation. And I think it has been a distinct honor to say that during my tenure as EIC, we have always had a plethora of voices, of authors from different countries, of genders, that have participated in the construction of those books. And it stands as a testament that we are a global community and we will always be one. Dr. Nathan Pennell: Well, thank you for that. And I'm happy to continue that as we move forward. Well, Don, thank you. It's been great speaking with you. You played such a pivotal role in the Ed Book's evolution and I'm so glad you were able to join me for our inaugural episode. Dr. Don Dizon: Well, I'm just tickled that you asked me to be your first guest. Thank you so much, Nate. Dr. Nathan Pennell: And I also want to thank our listeners for joining us today. We hope you'll join us again for more insightful views on topics you'll be hearing at the Education Sessions from ASCO meetings throughout the year, as well as our periodic deep dives on advances that are shaping modern oncology. Have a great day. Disclaimer: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity or therapy should not be construed as an ASCO endorsement. Follow today's speakers:   Dr. Nathan Pennell  @n8pennell @n8pennell.bsky.social   Dr. Don Dizon @drdondizon.bsky.social  Follow ASCO on social media:   @ASCO on X (formerly Twitter)   ASCO on Bluesky  ASCO on Facebook   ASCO on LinkedIn   Disclosures:  Dr. Nathan Pennell:      Consulting or Advisory Role: AstraZeneca, Lilly, Cota Healthcare, Merck, Bristol-Myers Squibb, Genentech, Amgen, G1 Therapeutics, Pfizer, Boehringer Ingelheim, Viosera, Xencor, Mirati Therapeutics, Janssen Oncology, Sanofi/Regeneron     Research Funding (Inst): Genentech, AstraZeneca, Merck, Loxo, Altor BioScience, Spectrum Pharmaceuticals, Bristol-Myers Squibb, Jounce Therapeutics, Mirati Therapeutics, Heat Biologics, WindMIL, Sanofi  Dr. Don Dizon: Stock and Other Ownership Interests: Midi, Doximity Honoraria: UpToDate, American Cancer Society Consulting or Advisory Role: AstraZeneca, Clovis Oncology, Kronos Bio, Immunogen Research Funding (Institution): Bristol-Myers Squibb          

Chuck Ryan joins us to discuss his interview with Felix and reflects on his keynote address at ASCO GU 2025.

Dr Thomas Hutson from UMC Cancer Center in Lubbock, Texas, Dr Rana McKay from UC San Diego Moores Cancer Center in California, Dr Tian Zhang from UT Southwestern Medical Center in Dallas, and moderator Dr Sumanta Kumar Pal from City of Hope Comprehensive Cancer Center in Duarte, California, discuss published data and updates from the 2025 ASCO Genitourinary Cancers Symposium meeting on management strategies for clear cell and non-clear cell renal cell carcinoma. CME information and select publications here.

Featuring perspectives from Dr Thomas E Hutson, Dr Rana R McKay, Dr Sumanta Kumar Pal and Dr Tian Zhang, moderated by Dr Pal, including the following topics: Introduction (0:00) Immunotherapeutic Strategies for Localized and Metastatic Clear Cell Renal Cell Carcinoma (RCC) — Dr Hutson (2:34) Optimal Management of Relapsed/Refractory RCC — Dr Zhang (32:49) Role of HIF-2α Inhibitors in the Treatment of Sporadic and von Hippel-Lindau-Associated RCC — Dr McKay (1:04:02) Current and Future Care of Patients with Non-Clear Cell RCC — Dr Pal (1:33:13) CME information and select publications

Dr Thomas Hutson from UMC Cancer Center in Lubbock, Texas, Dr Rana McKay from UC San Diego Moores Cancer Center in California, Dr Tian Zhang from UT Southwestern Medical Center in Dallas, and moderator Dr Sumanta Kumar Pal from City of Hope Comprehensive Cancer Center in Duarte, California, discuss published data and updates from the 2025 ASCO Genitourinary Cancers Symposium meeting on management strategies for clear cell and non-clear cell renal cell carcinoma. CME information and select publications here.

CME credits: 1.00 Valid until: 14-03-2026 Claim your CME credit at https://reachmd.com/programs/cme/collaborative-insights-to-solve-the-puzzle-of-bladder-cancer/30062/ This online educational activity, derived from a live satellite symposium at ASCO GU 2025, explores innovative strategies for personalized care in bladder cancer. Participants will gain a deeper understanding of molecular targets and profiling methodologies, review cutting-edge clinical trial evidence, and examine the latest advances in therapy delivery. The program also focuses on creating effective, evidence-based treatment plans and strategies for sequencing molecularly targeted therapies, as well as integrating interprofessional protocols for managing adverse events. This collaborative approach will equip learners with practical insights to enhance treatment outcomes in bladder cancer. =

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.

ASCOGU2025で発表された臨床試験の結果の解釈について忖度なしに議論しました！！

Dr. Neeraj Agarwal and Dr. Peter Hoskin discuss key abstracts in GU cancers from the 2025 ASCO Genitourinary Cancers Symposium, including novel therapies in prostate, bladder, and kidney cancer and the impact of combination therapies on patient outcomes. TRANSCSRIPT Dr. Neeraj Agarwal: Hello, and welcome to the ASCO Daily News Podcast. I'm Dr. Neeraj Agarwal, the director of the Genitourinary Oncology Program and professor of medicine at the Huntsman Cancer Institute at the University of Utah, and editor-in-chief of ASCO Daily News. Today, we'll be discussing practice-informing abstracts and other key advances in GU oncology featured at the 2025 ASCO Genitourinary Cancers Symposium. Joining me for this discussion is Dr. Peter Hoskin, the chair of this year's ASCO GU Symposium. Dr. Hoskin is a professor in clinical oncology in the University of Manchester and honorary consultant in clinical oncology at the Christie Hospital, Manchester, and University College Hospital London, in the United Kingdom. Our full disclosures are available in the transcript of this episode. Peter, thank you for joining us today. Dr. Peter Hoskin: Thank you so much, Neeraj. I am very pleased to be here. Dr. Neeraj Agarwal: The GU meeting highlighted remarkable advancements across the spectrum of GU malignancies. What stood out to you as the most exciting developments at the ASCO GU Symposium?  Dr. Peter Hoskin: The theme of this year's meeting was "Driving Innovation, Improving Patient Care," and this reflected ASCO GU's incredible milestone in GU cancer research over the years. We were thrilled to welcome almost 6,000 attendees on this occasion from over 70 countries, and most of them were attending in person and not online, although this was a hybrid meeting. Furthermore, we had more than 1,000 abstract submissions. You can imagine then that it fostered fantastic networking opportunities and facilitated valuable knowledge and idea exchanges among experts, trainees, and mentees. So, to start I'd like to come back to you for a second because the first day started with a focus on prostate cancer and some of the key clinical trials. And congratulations to you, Neeraj, on sharing the data from the TALAPRO-2 trial, which we were eagerly awaiting. I'd love to get your thoughts on the data that you presented. Could you tell us more about that trial, Abstract LBA18?  Dr. Neeraj Agarwal: Yes, Peter, I agree with you. It was such an exciting conference overall and thank you for your leadership of this conference. So, let's talk about the TALAPRO-2 trial. First of all, I would like to remind our audience that the combination of talazoparib plus enzalutamide was approved by the U.S. FDA in June 2023 in patients with metastatic castration-resistant prostate cancer harboring HRR gene alterations, after this combination improved the primary endpoint of radiographic progression-free survival compared to enzalutamide alone in the randomized, double-blind, placebo-controlled, multi-cohort phase 3 TALAPRO-2 trial. In the abstract I presented at ASCO GU 2025, we reported the final overall survival data, which was a key alpha-protected secondary endpoint in cohort 1, which enrolled an all-comer population of patients with mCRPC. So, at a median follow-up of around 53 months, in the intention-to-treat population, the combination of talazoparib plus enzalutamide significantly reduced the risk of death by 20% compared to enzalutamide alone, with a median OS of 45.8 months in the experimental arm versus 37 months in the control arm, which was an active control arm of enzalutamide. This improvement was consistent in patients with HRR alterations with a hazard ratio of 0.54 and in those with non-deficient or unknown HRR status, with a hazard ratio of 0.87. In a post hoc analysis, the hazard ratio for OS was 0.78 favoring the combination in those patients who did not have any HRR gene alteration in their tumors by both tissue and ctDNA testing. Consistent with the primary analysis, the updated rPFS data also favored the experimental arm with a median rPFS of 33.1 compared to 19.5 months in the control arm, and a hazard ratio of 0.667. No new safety signals were identified with extended follow-up. Thus, TALAPRO-2 is the first PARP inhibitor plus ARPI study to show a statistically significant and a clinically meaningful improvement in OS compared to standard-of-care enzalutamide as first-line treatment in patients with mCRPC unselected for HRR gene alterations. Dr. Peter Hoskin: Thank you, Neeraj. That's a great summary of the data presented and very important data indeed. There was another abstract also featured in the same session, Abstract 20, titled “Which patients with metastatic hormone-sensitive prostate cancer benefit more from androgen receptor pathway inhibitors? STOPCAP meta-analyses of individual participant data.” Neeraj, could you tell us more about this abstract? Dr. Neeraj Agarwal: Absolutely, I would be delighted to. So, in this meta-analysis, Dr. David Fischer and colleagues pooled individual participant data from different randomized phase 3 trials in the mHSPC setting to assess the potential ARPI effect modifiers and determine who benefits more from an ARPI plus ADT doublet. The primary outcome was OS for main effects and PFS for subgroup analyses. Prostate cancer specific survival was a sensitivity outcome. The investigators pooled data from 11 ARPI trials and more than 11,000 patients. Overall, there was a clear benefit of adding an ARPI on both OS and PFS, with hazard ratios of 0.66 and 0.51, respectively, representing a 13% and 21% absolute improvement at 5 years, respectively, with no clear difference by the class of agent. When stratifying the patients by age group, the effects of adding an ARPI on OS and PFS were slightly smaller in patients older than 75, than in those younger than 65, or aged between 65 and 75 years. Notably, in the trials assessing the use of abiraterone, we saw very little OS effects in the group of patients older than 75, however there was some benefit maintained in prostate-cancer specific survival, suggesting that other causes of death may be having an impact. The effects of the other ARPIs, or ‘lutamides' as I would call them, were similar across all three age subgroups on both OS and PFS. Therefore, the majority of patients with mHSPC benefit from the addition of ARPIs, and the benefits/risks of abiraterone and other ‘amides' must be considered in older patients.  Dr. Peter Hoskin: Thanks, Neeraj. Another great summary relevant to our day-to-day practice. Of course, there's ongoing collection of individual patient data from other key trials, which will allow robust comparison of ARPI doublet with triplet therapy (including docetaxel), guiding more personalized treatment.   Dr. Neeraj Agarwal: I agree with you, Peter, we need more data to help guide personalized treatment for patients with mHSPC and potentially guide de-escalation versus escalation strategies. Now, moving on to a different setting in prostate cancer, would you like to mention Abstract 17 titled, “Overall survival and quality of life with Lu-PSMA-617 plus enzalutamide versus enzalutamide alone in poor-risk, metastatic, castration-resistant prostate cancer in ENZA-p (ANZUP 1901),” presented by Dr. Louise Emmett? Dr. Peter Hoskin: Of course I will. So, ENZA-p was a multicenter, open-label, randomized, phase 2 trial conducted in Australia. It randomized 163 patients into adaptive doses (2 or 4 cycles) of Lu-PSMA-617 plus enzalutamide versus enzalutamide alone as first-line treatment in PSMA-PET-CT-positive, poor-risk, mCRPC. The interim analysis of ENZA-p with median follow-up 20 months showed improved PSA-progression-free survival with the addition of Lu-PSMA-617 to enzalutamide. Here, the investigators reported the secondary outcomes, overall survival, and health-related quality of life (HRQOL). After a median follow up of 34 months, overall survival was longer in the combination arm compared to the enzalutamide arm, with a median OS of 34 months compared to 26 months; with an HR of 0.55. Moreover, the combination improved both deterioration-free survival and health-related quality of life indicators for pain, fatigue, physical function, and overall health and quality of life compared to the control arm. Consistent with the primary analysis, the rPFS also favored the experimental arm with a median rPFS of 17 months compared to 14 months with a HR of 0.61. So, the addition of LuPSMA improved overall survival, and HRQOL in patients with high-risk mCRPC. Dr. Neeraj Agarwal: Thank you, Peter. Great summary, and promising results with Lu-177 and ARPI combination in first line treatment for mCRPC among patients who had two or more high risk features associated with early enzalutamide failure. Before we move on to bladder cancer, would you like to tell us about Abstract 15 titled, “World-wide oligometastatic prostate cancer (omPC) meta-analysis leveraging individual patient data (IPD) from randomized trials (WOLVERINE): An analysis from the X-MET collaboration,” presented by Dr. Chad Tang?  Dr. Peter Hoskin: Sure. So, with metastatic-directed therapy (MDT), we have a number of phase 2 studies making up the database, and the X-MET collaboration aimed to consolidate all randomized data on oligometastatic solid tumors. This abstract presented pooled individual patient data from all the published trials involving patients with oligometastatic prostate cancer who received MDT alongside standard of care (SOC) against SOC alone. The analysis included data from five trials, encompassing 472 patients with oligometastatic prostate cancer, and followed for a median of 41 months. Patients were randomly assigned in a 1:1 ratio to receive either MDT plus SOC or SOC alone. The addition of MDT significantly improved PFS. The median PFS was 32 months with MDT compared to 14.9 months with SOC alone, with an HR of 0.45. Subgroup analyses further confirmed the consistent benefits of MDT across different patient groups. Regardless of factors like castration status, receipt of prior primary treatment, stage, or number of metastases, MDT consistently improved PFS. In patients with mHSPC, MDT significantly delayed the time to castration resistance by nine months, extending it to a median of 72 months compared to 63 months in the SOC group with an HR of 0.58. In terms of OS, the addition of MDT improved the 48-month survival rate by 12%, with OS rates of 87% in the MDT+SOC group compared to 75% in the SOC alone group. Dr. Neeraj Agarwal: Thank you, Peter. These data demonstrate that adding MDT to systemic therapy significantly improves PFS, rPFS, and castration resistance-free survival, reinforcing its potential role in the treatment of oligometastatic prostate cancer. So, let's switch gears to bladder cancer and start with Abstract 658 reporting the OS analysis of the CheckMate-274 trial. Would you like to tell us about this abstract?  Dr. Peter Hoskin: Yes, sure, Neeraj. This was presented by Dr. Matt Milowsky, and it was additional efficacy outcomes, including overall survival, from the CheckMate-274 trial which evaluated adjuvant nivolumab versus placebo in patients with high-risk muscle-invasive bladder cancer after radical surgery. The phase 3 trial previously demonstrated a significant improvement in disease-free survival with nivolumab. With a median follow-up of 36.1 months, disease-free survival was longer with nivolumab compared to placebo across all patients with muscle-invasive bladder cancer, reducing the risk of disease recurrence or death by 37%. Among patients who had received prior neoadjuvant cisplatin-based chemotherapy, nivolumab reduced this risk by 42%, whilst in those who had not received chemotherapy, the risk was reduced by 31%. Overall survival also favored nivolumab over placebo, reducing the risk of death by 30% in all patients with muscle-invasive bladder cancer and by 52% in those with tumors expressing PD-L1 at 1% or higher. Among patients who had received prior neoadjuvant chemotherapy, nivolumab reduced the risk of death by 26%, whilst in those who had not received chemotherapy, the risk was reduced by 33%. Alongside this, the safety profile remained consistent with previous findings. Dr. Neeraj Agarwal: Thank you, Peter, for such a nice overview of this abstract. These results reinforce adjuvant nivolumab as a standard of care for high-risk muscle-invasive bladder cancer, offering the potential for a curative outcome for our patients. Dr. Peter Hoskin: I agree with you Neeraj. Perhaps you would like to mention Abstract 659 titled, “Additional efficacy and safety outcomes and an exploratory analysis of the impact of pathological complete response (pCR) on long-term outcomes from NIAGARA.” Dr. Neeraj Agarwal: Of course. Dr. Galsky presented additional outcomes from the phase 3 NIAGARA study, which evaluated perioperative durvalumab combined with neoadjuvant chemotherapy in patients with muscle-invasive bladder cancer. The study previously demonstrated a significant improvement in event-free survival and overall survival with durvalumab compared to chemotherapy alone, with a manageable safety profile and no negative impact on the ability to undergo radical cystectomy. Among the 1,063 randomized patients, those who received durvalumab had a 33% reduction in the risk of developing distant metastases or death and a 31% reduction in the risk of dying from bladder cancer compared to those who received chemotherapy alone. More patients who received durvalumab achieved a pathological complete response at the time of surgery with 37% compared to 28% in the chemotherapy-alone group. Patients who achieved a pathological complete response had better event-free survival and overall survival compared to those who did not. In both groups, durvalumab provided additional survival benefits, reducing the risk of disease progression or death by 42% and the risk of death by 28% in patients with a pathological complete response, while in those patients without a pathological complete response, the risk of disease progression or death was reduced by 23% and the risk of death by 16% when durvalumab was added to the chemotherapy. Immune-mediated adverse events occurred in 21% of patients in the durvalumab group compared to 3% in the chemotherapy-alone group, with grade 3 or higher events occurring in 3% compared to 0.2%. The most common immune-related adverse events included hypothyroidism in 10% of patients treated with durvalumab compared to 1% in the chemotherapy-alone group, and hyperthyroidism in 3% versus 0.8%. At the time of the data cutoff, these adverse events had resolved in 41% of affected patients in the durvalumab group and 44% in the chemotherapy-alone group. Dr. Peter Hoskin: Thank you, Neeraj, for the great summary. These findings further support the role of perioperative durvalumab as a potential standard of care for patients with muscle-invasive bladder cancer. Dr. Neeraj Agarwal: I concur with your thoughts, Peter. Before wrapping up the bladder cancer section, would you like to mention Abstract 664 reporting updated results from the EV-302 trial, which evaluated enfortumab vedotin in combination with pembrolizumab compared to chemotherapy as first-line treatment for patients with previously untreated locally advanced or metastatic urothelial carcinoma? Dr. Peter Hoskin: Yes, of course. Dr. Tom Powles presented updated findings from the EV-302 study, and in this abstract presented 12 months of additional follow-up for EV-302 (>2 y of median follow-up) and an exploratory analysis of patients with confirmed complete response (cCR). The study had a median follow-up of 29.1 months and previously demonstrated significant improvements in progression-free survival and overall survival with enfortumab vedotin and pembrolizumab. This is now the standard of care in global treatment guidelines. Among the 886 randomized patients, enfortumab vedotin and pembrolizumab reduced the risk of disease progression or death by 52% and the risk of death by 49% compared to chemotherapy. The survival benefit was consistent regardless of cisplatin eligibility or the presence of liver metastases. The confirmed objective response rate was higher with enfortumab vedotin and pembrolizumab at 67.5% compared to 44.2% with chemotherapy. The median duration of response was 23.3 months with enfortumab vedotin and pembrolizumab compared to 7.0 months with chemotherapy. A complete response was achieved in 30.4% of patients in the enfortumab vedotin and pembrolizumab group compared to 14.5% in the chemotherapy group, with the median duration of complete response not yet reached in the enfortumab vedotin and pembrolizumab group compared to 15.2 months in the chemotherapy group. Severe treatment-related adverse events occurred in 57.3% of patients treated with enfortumab vedotin and pembrolizumab compared to 69.5% in the chemotherapy group, while in patients who achieved a complete response, severe adverse events occurred in 61.7% of those treated with enfortumab vedotin and pembrolizumab compared to 71.9% with chemotherapy. Treatment-related deaths were reported in 1.1% of patients treated with enfortumab vedotin and pembrolizumab compared to 0.9% with chemotherapy, with no treatment-related deaths occurring in those who achieved a complete response. These findings clearly confirm the durable efficacy of enfortumab vedotin and pembrolizumab, reinforcing its role as the standard of care for the first-line treatment of patients with locally advanced or metastatic urothelial carcinoma, and no new safety concerns have been identified. Dr. Neeraj Agarwal: Thank you for this great summary. Moving on to kidney cancer, let's talk about Abstract 439 titled, “Nivolumab plus cabozantinib (N+C) vs sunitinib (S) for previously untreated advanced renal cell carcinoma (aRCC): Final follow-up results from the CheckMate-9ER trial.” Dr. Peter Hoskin: Sure. Dr. Motzer presented the final results from the phase 3 CheckMate-9ER trial, which compared the combination of cabozantinib and nivolumab against sunitinib in previously untreated advanced renal cell carcinoma. The data after more than five years follow-up show that the combination therapy provided sustained superior efficacy compared to sunitinib. In terms of overall survival, we see an 11-month improvement in median OS, 46.5 months for the cabo-nivo versus 35.5 months for sunitinib and a 42% reduction in the risk of disease progression or death, with median progression-free survival nearly doubling – that's 16.4 months in the combination group and 8.3 months with sunitinib. Importantly, the safety profile was consistent with the known safety profiles of the individual medicines, with no new safety concerns identified. Dr. Neeraj Agarwal: Great summary, Peter. These data further support the efficacy of cabo-nivo combination therapy in advanced renal cell carcinoma, which is showing a 11-month difference in overall survival. Dr. Peter Hoskin: Neeraj, before wrapping up this podcast, would you like to tell us about Abstract 618? This is titled “Prospective COTRIMS (Cologne trial of retroperitoneal lymphadenectomy in metastatic seminoma) trial: Final results.” Dr. Neeraj Agarwal: Sure, Peter. I would be delighted to. Dr Heidenrich from the University of Cologne in Germany presented the COTRIMS data evaluating retroperitoneal LN dissection in patients with clinical stage 2A/B seminomas. Seminomas are classified as 2A or B when the disease spreads to the retroperitoneal lymph nodes of up to 2 cm (CS IIA) or of more than 2 cm to up to 5 cm (CS 2B) in maximum diameter, respectively. They account for 10-15% of seminomas and they are usually treated with radiation and chemotherapy. However, radiation and chemo can be associated with long-term toxicities such as cardiovascular toxicities, diabetes, solid cancers, leukemia, particularly for younger patients. From this standpoint, Dr Heidenrich and colleagues evaluated unilateral, modified template, nerve-sparing retroperitoneal lymph node dissection as a less toxic alternative compared to chemo and radiation. They included 34 patients with negative AFP, beta-HCG, and clinical stage 2A/B seminomas. At a median follow-up of 43.2 months, the trial demonstrated great outcomes: a 99.3% treatment-free survival rate and 100% overall survival, with only four relapses. Antegrade ejaculation was preserved in 88% of patients, and severe complications such as grade 3 and 4 were observed in 12% of patients. Pathological analysis revealed metastatic seminoma in 85% of cases, with miR371 being true positive in 23 out of 24 cases and true negative in 100% of cases. It appears to be a valid biomarker for predicting the presence of lymph node metastases. These findings highlight retroperitoneal lymph node dissection is feasible; it has low morbidity, and excellent oncologic outcomes, avoiding overtreatment in 80% of patients and sparing unnecessary chemotherapy or radiotherapy in 10-15% of cases. Dr. Peter Hoskin: Great summary and important data on retroperitoneal lymphadenectomy in metastatic seminoma. These findings will help shape clinical practice. Any final remarks before we conclude today's podcast? Dr. Neeraj Agarwal: Before wrapping up this podcast, I would like to say that we have reviewed several abstracts addressing prostate, bladder, kidney cancers, and seminoma, which are impacting our medical practices now and in the near future. Peter, thank you for sharing your insights with us today. These updates are undoubtedly exciting for the entire GU oncology community, and we greatly appreciate your valuable contribution to the discussion and your leadership of the conference. Many thanks. Dr. Peter Hoskin: Thank you, Neeraj. Thank you for the opportunity to share this information more widely. I'm aware that whilst we have nearly 6,000 delegates, there are many other tens of thousands of colleagues around the world who need to have access to this information. And it was a great privilege to chair this ASCO GU25. So, thank you once again, Neeraj, for this opportunity to share more of this information that we discussed over those few days. Dr. Neeraj Agarwal: Thank you, Peter. And thank you to our listeners for joining us today. You will find links to the abstracts discussed today on the transcript of this episode. Finally, if you value the insights that you hear on the ASCO Daily News podcast, please take a moment to rate, review, and subscribe wherever you get your podcasts. Disclaimer: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity or therapy should not be construed as an ASCO endorsement.  Find out more about today's speakers:   Dr. Neeraj Agarwal    @neerajaiims    Dr. Peter Hoskin Follow ASCO on social media:      @ASCO on Twitter      ASCO on Bluesky  ASCO on Facebook      ASCO on LinkedIn      Disclosures: Dr. Neeraj Agarwal: Consulting or Advisory Role: Pfizer, Bristol-Myers Squibb, AstraZeneca, Nektar, Lilly, Bayer, Pharmacyclics, Foundation Medicine, Astellas Pharma, Lilly, Exelixis, AstraZeneca, Pfizer, Merck, Novartis, Eisai, Seattle Genetics, EMD Serono, Janssen Oncology, AVEO, Calithera Biosciences, MEI Pharma, Genentech, Astellas Pharma, Foundation Medicine, and Gilead Sciences Research Funding (Institution): Bayer, Bristol-Myers Squibb, Takeda, Pfizer, Exelixis, Amgen, AstraZeneca, Calithera Biosciences, Celldex, Eisai, Genentech, Immunomedics, Janssen, Merck, Lilly, Nektar, ORIC Pharmaceuticals, Crispr Therapeutics, Arvinas Dr. Peter Hoskin: Research Funding (Institution): Varian Medical Systems, Astellas Pharma, Bayer, Roche, Pfizer, Elekta, Bristol Myers  

Silke joins Tom and Brian to discuss highlights form ASCO GU 2025

Episode 19 is the final part of a mini-series from the 2025 ASCO Genitourinary Cancers Symposium in San Francisco! After diving into prostate and bladder cancers in the first two episodes, Dr. Aly-Khan Lalani and Dr. Christopher Wallis are wrapping with an in-depth look at kidney cancer, diving into research, studies and developments shared at the symposium. The View on GU with Lalani & Wallis integrates key clinical data from major conferences and high impact publications, sharing meaningful take-home messages for practicing clinicians in the field of genitourinary (GU) cancers. Learn more about The View on GU: theviewongu.caThis podcast has been made possible through unrestricted financial support by Bayer, Astellas, J&J, Tolmar, Merck, and Pfizer.

Dr. Aly-Khan Lalani and Dr. Christopher Wallis reflect on the 2025 ASCO Genitourinary Cancers Symposium, with a focus on bladder cancer. This is the second part of a three-episode series filmed live in San Francisco.The View on GU with Lalani & Wallis integrates key clinical data from major conferences and high impact publications, sharing meaningful take-home messages for practicing clinicians in the field of genitourinary (GU) cancers. This podcast has been made possible through unrestricted financial support by Bayer, Astellas, J&J, Tolmar, Merck, and Pfizer.

Today we will be discussing a few of the exciting abstracts presented at ASCO GU (Feb 13-15 2025) for prostate CA (TALAPRO-2), bladder CA (EV-302, CM-274, NIAGARA), and RCC (COSMIC-313, KIM-1).

Dr. Aly-Khan Lalani and Dr. Christopher Wallis discuss new findings, novel treatment approaches, and research surrounding prostate cancer from their time at the 2025 ASCO GU Symposium. This can't-miss special is the first of three episodes recorded live from San Francisco!The View on GU with Lalani & Wallis integrates key clinical data from major conferences and high impact publications, sharing meaningful take-home messages for practicing clinicians in the field of genitourinary (GU) cancers. Learn more about The View on GU: theviewongu.caThis podcast has been made possible through unrestricted financial support by Bayer, Astellas, J&J, Tolmar, Merck, and Pfizer.

Toni Choueiri discusses the updated data from different cohorts of this novel HIF inhibitor.

Laurence Albiges joins the show to discuss novel combos in refractory RCC and an update of the Ipi/Nivo/Cabo COSMIC OS data

Vincent Xu discusses this emerging RCC biomarker and data from the Checkmate 214 trial

Gopa Iyer from MSKCC joins the show to discuss his initial results from this phase 2 trial.

Matt Galsky joins the show to discuss pCR in NIAGARA and clinical implications.

Xinan Sheng. M.D., Professor in the Department of Genitourinary Oncology at Peking University Cancer Hospital &institute in Beijing, China joins us to discuss the update of this trial and impressive pCR rates.

Tanya Dorff from City of Hope joins us to discuss clinical implications of these data and also comment on TALAPRO-2

Neeraj Aggarwal joins Tom and Brian for an in-depth look at these important data

A breaking news podcast from ASCO GU in San Francisco! Prof Louise Emmett (St Vincent's, Sydney), has just read out the latest update from the ENZA-P trial (and simultaneous publication in Lancet Oncology), reporting that the combination of LuPSMA and enzalutamide improves overall survival when compared with enzalutamide alone, in men with poor prognosis mCRPC. Big news!! A 45% reduction in the risk of death in favour of the combination. Plus excellent quality of life for those receiving the combo. We are joined by Louise and co-author A/Prof Andrew Weickhardt (Austin Health, Melbourne), to discuss this exciting data from the ENZA-P trial, and what it means for the future of not just mCRPC, but also for similar combinations in mHSPC.ENZA-P is an investigator-initiated Phase II trial led by ANZUP in partnership with the Prostate Cancer Research Alliance, a join initiative between the Australian Government and Movember. Your co-hosts as ever are Professor Declan Murphy and Dr Renu Eapen. This is a Themed podcast supported by our Gold Partners, Astellas, and our Silver Partners, Novartis. Even better on our YouTube channelLinks:Lancet Oncology paperANZUP 

Today we will be discussing exciting data to come at ASCO GU (Feb 13-15 2025) in terms of research for prostate CA, bladder CA, RCC and other rarer GU tumors.

Silke Gillessen joins Brian and Tom and they discuss what to look forward to in prostate, bladder and RCC at ASCO GU 2025.