Oncology Decoded

In the newest episode of Oncology Decoded, hosts Manojkumar Bupathi, MD, MS, and Benjamin Garmezy, MD, convened with their colleagues Suzanne B. Merrill, MD, FACS, and Mark D. Tyson, II, MD, MPH. They broke down the current treatment paradigm for those with non–muscle-invasive bladder cancer (NMIBC) by discussing how novel therapeutic modalities, patient selection criteria, and other practical considerations fit into effective clinical strategies. The discussion began with an overview of the effectiveness and limitations associated with Bacillus Calmette-Guérin (BCG), and how clinical trials like the phase 3 KEYNOTE-676 (NCT03711032) and phase 3 POTOMAC (NCT03528694) studies may support novel treatment regimens that incorporate checkpoint inhibitors. The group discussed how immunotherapy agents like pembrolizumab (Keytruda) may play important roles in the treatment of patients with NMIBC, especially in the event of BCG-unresponsive disease or BCG shortages. Additionally, the experts spoke about forming effective collaborations between urologists and medical oncologists to optimally care for patients. Specifically, Merrill emphasized a dedicated team approach to check symptoms, process referrals, and handle other tasks when treating patients who are receiving immune checkpoint inhibitors for their diseases. The conversation concluded with the group emphasizing the development of novel treatment delivery systems across the NMIBC space, which may improve outcomes and positively impact patients from a quality-of-life perspective.Drs. Bupathi and Garmezy are executive cochairs of the Genitourinary Cancer Research Executive Committee at Sarah Cannon Research Institute (SCRI). Additionally, Dr. Bupathi is president and a medical oncologist with Rocky Mountain Cancer Centers, specializing in solid tumors and genitourinary cancers. Dr. Garmezy is the associate director of genitourinary research for SCRI and a medical oncologist at SCRI Oncology Partners, specializing in genitourinary cancers.Merill is a board-certified urologic surgeon at Colorado Urology. Tyson is a urologic oncologist with a subspecialty interest in bladder cancer at Mayo Clinic in Arizona.

In the latest episode of Oncology Decoded, hosts Manojkumar Bupathi, MD, MS; and Benjamin Garmezy, MD, spoke about the clinical utility of enfortumab vedotin-ejfv (Padcev) plus pembrolizumab (Keytruda) for those with muscle-invasive bladder cancer (MIBC) and similar patient populations. They highlighted the “transformational” potential of this therapeutic regimen in the context of findings from the phase 3 KEYNOTE-B15/EV-304 trial (NCT04700124) that investigators presented at the 2026 ASCO Genitourinary Cancers Symposium.Although certain data from the EV-304 trial, including the improvements in pathologic complete responses (pCRs) with the enfortumab vedotin combination over gemcitabine/cisplatin, represent “historical gamechangers”, the hosts pointed towards some uncertainty related to outcomes for those with varying or mixed histologies. According to Bupathi, it may still make sense to administer chemotherapy with immunotherapy in some of these subgroups. The hosts also considered how many cycles of enfortumab vedotin plus pembrolizumab should be administered across the neoadjuvant and adjuvant settings, noting how markers like circulating tumor DNA may help inform treatment schedules. Additionally, they highlighted a need for additional research to clarify whether cystectomy could be spared for patients receiving this combination regimen while translating the benefits observed in trials like EV-304 to the real world.The discussion also touched upon the treatment of those with metastatic disease, as the hosts considered how dosing cycles, consolidated radiotherapy, and cystectomy with nodal dissection fit into the treatment algorithm for these patients. Garmezy and Bupathi also discussed how the efficacy and safety of the enfortumab vedotin combination compared with gemcitabine plus nivolumab (Opdivo), noting how the EV-304 regimen may be simpler to administer and manage.Bupathi and Garmezy are executive cochairs of the Genitourinary Cancer Research Executive Committee at Sarah Cannon Research Institute (SCRI). Additionally, Bupathi is president of and a medical oncologist with Rocky Mountain Cancer Centers, specializing in solid tumors and genitourinary cancers. Garmezy is the associate director of genitourinary research for SCRI and a medical oncologist at SCRI Oncology Partners, specializing in genitourinary cancers.ReferenceGalsky MD, Valderrama BP, Maruzzo M, et al. Neoadjuvant and adjuvant enfortumab vedotin (EV) plus pembrolizumab (pembro) for participants with muscle-invasive bladder cancer (MIBC) who are eligible for cisplatin: Randomized, open-label, phase 3 KEYNOTE-B15 study. J Clin Oncol. 2026;44(suppl 7):LBA630. doi: 10.1200/JCO.2026.44.7_suppl.LBA630

Following the 2026 American Society of Clinical Oncology (ASCO) Genitourinary Cancers Symposium, Oncology Decoded hosts Manojkumar Bupathi, MD, MS; and Benjamin Garmezy, MD, met to break down the key trials and presentations that may help move the needle in genitourinary oncology. Together, they reviewed findings and clinical implications across various bladder cancer, kidney cancer, and prostate cancer populations.Among several sessions highlighted during their discussion, the experts covered the following presentations:1.        Phase 3 KEYNOTE-B15 Trial (NCT04700124)a.        Enfortumab vedotin-ejfv (Padcev) plus pembrolizumab (Keytruda) significantly prolonged event-free survival (EFS) outcomes vs gemcitabine plus cisplatin among patients with muscle-invasive bladder cancer (MIBC; HR, 0.53; 95% CI, 0.41-0.70; P <.001).b.       The rate of pathological complete response also improved by an estimated difference of 23.4% (95% CI, 16.7%-29.8%; P <.001) with the enfortumab vedotin combination.c.        Data from this trial point towards the potential removal of chemotherapy in the perioperative therapy landscape.2.        Phase 3 LITESPARK-011 Trial (NCT04586231)a.        Belzutifan (Welireg) plus lenvatinib (Lenvima) improved progression-free survival (PFS; HR, 0.70; 95% CI, 0.59-0.84; P = .00007) and responses vs cabozantinib (Cabometyx) monotherapy among those with advanced clear cell renal cell carcinoma.b.       Data showed a median duration of response (DOR) of 23.0 months with the belzutifan combination vs 12.3 months with cabozantinib.c.        Findings may support an eventual FDA approval of belzutifan/lenvatinib in this patient population.3.        Phase 3 PEACE-3 Trial (NCT02194842)a.        Combining enzalutamide (Xtandi) with radium-223 (Xofigo) boosted overall survival (OS) compared with enzalutamide alone among patients with metastatic castration-resistant prostate cancer (HR, 0.75; 95% CI, 0.60-0.95; P = .0078).b.       Previously reported rPFS improvements with the combination were sustained with longer follow-up, as data showed a median rPFS of 19.2 months vs 16.4 months in the experimental and comparator arms, respectively.Drs. Bupathi and Garmezy are executive cochairs of the Genitourinary Cancer Research Executive Committee at Sarah Cannon Research Institute (SCRI). Additionally, Dr. Bupathi is president and a medical oncologist with Rocky Mountain Cancer Centers, specializing in solid tumors and genitourinary cancers. Dr. Garmezy is the associate director of genitourinary research for SCRI and a medical oncologist at SCRI Oncology Partners, specializing in genitourinary cancers.References Galsky MD, Valderrama BP, Maruzzo M, et al. Neoadjuvant and adjuvant enfortumab vedotin (EV) plus pembrolizumab (pembro) for participants with muscle-invasive bladder cancer (MIBC) who are eligible for cisplatin: randomized, open-label, phase 3 KEYNOTE-B15 study. J Clin Oncol. 2026;44(suppl 7):LBA630. doi:10.1200/JCO.2026.44.7_suppl.LBA630 Motzer RJ, Park SH, McDermott RS, et al. Belzutifan (bel) plus lenvatinib (lenva) versus cabozantinib (cabo) for advanced renal cell carcinoma (RCC) after anti-PD-(L)1 therapy: open-label phase 3 LITESPARK-011 study. J Clin Oncol. 2026;44(suppl 7):417. doi:10.1200/JCO.2026.44.7_suppl417 Gallardo E, Tombal BF, Saad F, et al. Final overall survival results from the EORTC 1333/PEACE-3 trial: enzalutamide with or without radium-223 in metastatic castration-resistant prostate cancer. J Clin Oncol. 2026;44(suppl 7):15. doi:10.1200/JCO.2026.44.7_suppl.15

In the latest episode of Oncology Decoded, hosts Manojkumar Bupathi, MD, MS; and Benjamin Garmezy, MD, convened with Meredith Pelster, MD, MSCI; and Jason Henry, MD. Together, they looked back at the presentations and data shared at the 2026 ASCO Gastrointestinal Cancers Symposium that may have long-term impacts on community oncology practice across different gastrointestinal (GI) malignancies, including pancreatic cancer and colorectal cancer (CRC).Trials and sessions of interest included the following:Phase 1 Trial (NCT06179160) of INCB161734o   INCB161734, an investigational KRAS G12D small molecule inhibitor, displayed a manageable safety profile among patients with advanced or metastatic pancreatic ductal adenocarcinoma.o   The agent produced a disease control rate of 73% (n = 16/22) given at 600 mg once daily and 86% (n = 25/29) when given at 1200 mg once daily.Phase 3 BREAKWATER Trial (NCT04607421)o   Among those with BRAF V600E-mutated metastatic CRC, encorafenib (Braftovi) plus cetuximab (Erbitux) and chemotherapy improved the overall response rate (ORR) at 64.4% vs 39.2% with chemotherapy with or without bevacizumab (Avastin) in the control arm (OR, 2.76; 95% CI, 1.42-5.35; P = .001).o   Overall, the data supported the encorafenib-based combination as a new potential standard of care in BRAF V600E-mutated metastatic CRC.o   The FDA recently granted traditional approval to the encorafenib regimen based on data from the BREAKWATER trial.Phase 3 COMMIT Trial (NCT02997228)o   Chemotherapy in combination with bevacizumab and atezolizumab (Tecentriq) improved outcomes among patients with mismatch repair deficient (dMMR) or microsatellite instability–high (MSI-H) metastatic CRC vs atezolizumab alone.o   Data showed a median progression-free survival (PFS) of 30.0 months vs 4.3 months in the combination and monotherapy arms, respectively.Bupathi is the executive cochair of the Genitourinary Cancer Research Executive Committee at Sarah Cannon Research Institute (SCRI) and a medical oncologist with Rocky Mountain Cancer Centers, specializing in solid tumors and genitourinary cancers. Garmezy is the associate director of genitourinary research and executive cochair of the Genitourinary Cancer Research Executive Committee at SCRI and a medical oncologist at SCRI Oncology Partners, specializing in genitourinary cancers.Pelster is associate director of GI Cancer Research at SCRI Oncology Partners and specializes in treating GI cancers as well as head and neck cancers. Henry is associate director of Drug Development at Sarah Cannon.References Wainberg ZA, Henry JT, Park H, et al. Preliminary phase 1 results of INCB161734, a novel oral Kirsten rat sarcoma (KRAS) G12D inhibitor, as monotherapy or in combination with chemotherapy for advanced/metastatic pancreatic duct adenocarcinoma (PDAC). J Clin Oncol. 2026;44(suppl 2):654. doi:10.1200/JCO.2026.44.2_suppl.654 Kopetz S, Wasan HS, Yoshino HS, et al. BREAKWATER: primary analysis of first-line (1L) encorafenib + cetuximab (EC) + FOLFIRI in BRAF V600E-mutant metastatic colorectal cancer (mCRC). J Clin Oncol. 2026;44(suppl 2):13. doi:10.1200/JCO.2026.44.2_suppl.13 FDA grants traditional approval to encorafenib for metastatic colorectal cancer with a BRAF V600E mutation. News release. FDA. February 24, 2026. Accessed February 25, 2026. https://tinyurl.com/4xr84a6y Rocha Lima CMS, Yothers G, George TJ, et al. Colorectal Cancer Metastatic dMMR Immunotherapy (COMMIT) study: a randomized phase III study of atezolizumab (atezo) monotherapy versus mFOLFOX6/bevacizumab/atezo (FFX/bev) in the first-line treatment of patients (pts) with deficient DNA mismatch repair (dMMR) or microsatellite instability-high (MSI-H) metastatic colorectal cancer (mCRC)— NRG-GI004/SWOG-S1610. J Clin Oncol. 2026;44(suppl 2):14. doi:10.1200/JCO.2026.44.2_suppl.14

In a special episode of Oncology Decoded, hosts Manojkumar Bupathi, MD, MS, and Benjamin Garmezy, MD, spoke with their colleague Debapriya Mondal, MBBS, MD, DrNB, who connected to the conversation from India. Collectively, the trio reviewed how clinical practice may differ in US- and India-based institutions, specifically as it relates to the treatment of patients with prostate cancer. According to Mondal, while prostate cancer does not represent one of the top 5 most diagnosed cancer types in India overall, patients appear to present with disease more often in cities like New Delhi, Kolkata, and Bangalore. Additionally, many patients in India appear to be diagnosed with more advanced stages of disease compared with reports in the US. Regarding medical practices in the US and India, the group discussed potential differences in treatment pathways and specialties that are initially involved in care. Additionally, they highlighted how urologists decide on sequencing androgen deprivation therapy, androgen receptor pathway inhibitors, and other modalities based on region-specific considerations.The conversation also touched upon the costs of various therapies between regions, as Mondal outlined how patients in India may have access to cheaper generic products for reference drugs like olaparib (Lynparza) and rucaparib (Rubraca). Despite other differences in terms of insurance coverage and barriers to treatment access between regions, the group noted certain international similarities in their respective treatment models, including strategies for the management of advanced or localized disease. Bupathi is the executive cochair of the Genitourinary Cancer Research Executive Committee at Sarah Cannon Research Institute (SCRI) and a medical oncologist with Rocky Mountain Cancer Centers, specializing in solid tumors and genitourinary cancers. Garmezy is the associate director of genitourinary research and executive cochair of the Genitourinary Cancer Research Executive Committee at SCRI and a medical oncologist at SCRI Oncology Partners, specializing in genitourinary cancers. Mondal is a consultant medical oncologist from Foris Healthcare in Kolkata, West Bengal, India.

In the latest episode of Oncology Decoded, hosts Manojkumar Bupathi, MD, MS, and Benjamin Garmezy, MD, wound the clock back to 2025 to discuss the key findings and clinical developments that may propel the genitourinary oncology field forward. Following a breakdown of last year’s breakthroughs in kidney cancer and bladder cancer care, the hosts reviewed the biggest headlines and milestones of 2025 related to prostate cancer management and research. Bupathi is the executive cochair of the Genitourinary Cancer Research Executive Committee at Sarah Cannon Research Institute (SCRI) and a medical oncologist with Rocky Mountain Cancer Centers, specializing in solid tumors and genitourinary cancers. Garmezy is the associate director of genitourinary research and executive cochair of the Genitourinary Cancer Research Executive Committee at SCRI and a medical oncologist at SCRI Oncology Partners, specializing in genitourinary cancers. Together, they spoke about several major prostate cancer happenings throughout 2025, including but not limited to:·      The FDA Approval of the Phase 3 ARANOTE Trial (NCT04736199) Regimeno   In June 2025, the FDA approved darolutamide (Nubeqa) for patients with metastatic castration-sensitive prostate cancer (CSPC) based on findings from the phase 3 ARANOTE trial.o   Topline data showed a median radiographic progression-free survival (rPFS) that was not reached (NR) with darolutamide vs 25 months (95% CI, 19-NR) with placebo (HR, 0.54; 95% CI, 0.41-0.71; P <.0001).o   This approval may grant easier access to darolutamide, especially for the treatment of patients who are older or who present with certain neurocognitive disorders.·      The FDA Approval of the Phase 3 AMPLITUDE Trial (NCT04497844) Regimeno   December 2025 saw the FDA approval of niraparib and abiraterone acetate (Akeega) plus prednisone for adults with suspected or deleterious BRCA2-mutated CSPC.o   Supporting data from the phase 3 AMPLITUDE trial showed a median rPFS that was not estimable (NE; 95% CI, 41 months-NE) in the niraparib arm vs 26 months (95% CI, 18-28) in the placebo arm among 323 patients with BRCA2-mutated disease.o   This approval for patients with BRCA2-mutations reinforces the importance of conducting upfront genetic testing.·      Phase 3 PSMAddition Trial (NCT04720157)o   Lutetium Lu 177 vipivotide tetraxetan (Pluvicto) plus an androgen receptor pathway inhibitor (ARPI) and androgen deprivation therapy (ADT) significantly prolonged rPFS vs ARPI/ADT treatment alone among patients with prostate specific-membrane antigen (PSMA)–positive metastatic hormone-sensitive prostate cancer (HR, 0.72; 95% CI, 0.58-0.90; P = .002).o   Other data from ESMO Congress 2025 showed that the lutetium Lu 177 combination numerically improved the overall response rate at 85.3% (95% CI, 79.9%-89.6%) vs 80.8% (95% CI, 74.8%-85.8%) in the control arm.o   The safety profile observed in the trial may raise questions over whether it is worthwhile to administer all 6 cycles of lutetium Lu 177 to patients. References FDA approves darolutamide for metastatic castration-sensitive prostate cancer. News release. FDA. June 3, 2025. Accessed January 20, 2026. https://tinyurl.com/yhde24zj FDA approves niraparib and abiraterone acetate plus prednisone for BRCA2-mutated metastatic castration-sensitive prostate cancer. News release. FDA. December 12, 2025. Accessed January 20, 2026. https://tinyurl.com/rcxaj98 Tagawa ST, Sartor O, Piulats JM, et al. Phase III trial of [177Lu]Lu-PSMA-617 combined with ADT + ARPI in patients with PSMA-positive metastatic hormone-sensitive prostate cancer (PSMAddition). Ann Oncol. 2025;36(suppl 2):S1627-S1628. doi:10.1016/j.annonc.2025.09.101

As part of ushering in the new year, Oncology Decoded hosts Manojkumar Bupathi, MD, MS, and Benjamin Garmezy, MD, looked back on the most exciting advancements that shook up the genitourinary oncology landscape throughout 2025. Specifically, they highlighted the clinical trial readouts, regulatory milestones, and other breakthroughs that made 2025 a “remarkable year” in kidney cancer and bladder cancer care.Bupathi is the executive cochair of the Genitourinary Cancer Research Executive Committee at Sarah Cannon Research Institute (SCRI) and a medical oncologist with Rocky Mountain Cancer Centers, specializing in solid tumors and genitourinary cancers. Garmezy is the associate director of genitourinary research and executive cochair of the Genitourinary Cancer Research Executive Committee at SCRI and a medical oncologist at SCRI Oncology Partners, specializing in genitourinary cancers. Together, they reviewed several key moments in kidney and bladder cancer research, including but not limited to:·      The FDA Approval of The EV-303 Trial (NCT03924895) Regimeno   In November 2025, the FDA approved a neoadjuvant/adjuvant regimen consisting of pembrolizumab (Keytruda) or pembrolizumab and berahyaluronidase alfa-pmph (Keytruda Qlex) plus enfortumab vedotin-ejfv (Padcev) for patients with muscle-invasive bladder cancer (MIBC) who are ineligible for cisplatin.o   “Incredible” data from the phase 3 KEYNOTE-905/EV-303 trial supported the approval, which showed an improvement in event-free survival with the enfortumab vedotin combination vs surgery alone (HR, 0.40; 95% CI, 0.28-0.57; P <.0001).o   The approval may lead to a “paradigm shift” in the treatment of this MIBC population. ·      The Phase 3 POTOMAC Trial (NCT03528694)o   Data showed a meaningful disease-free survival (DFS) improvement when adding durvalumab (Imfinzi) to Bacillus Calmette-Guérin (BCG) among patients with BCG-naïve, high-risk NMIBC (HR, 0.68; 95% CI, 0.50-0.93; P = .0154).o   Frontline immunotherapy-based regimens may “complicate” how to think about treating patients with NMIBC later down the line.·      The Phase 3 RAMPART Trial (NCT03288532)o   Adjuvant treatment with durvalumab (Imfinzi) plus tremelimumab-actl (Imjudo) improved DFS compared with active monitoring among patients who underwent resection of primary renal cell carcinoma (RCC; HR, 0.65; 95% CI, 0.45-0.93; P = .0094).o   Following previous unsuccessful trials assessing immunotherapy in adjuvant RCC, the results of RAMPART demonstrate how immunotherapy can work in this space.References FDA approves pembrolizumab with enfortumab vedotin-ejfv for muscle invasive bladder cancer. News release. FDA. November 21, 2025. Accessed January 5, 2026. https://tinyurl.com/bdfhmhnk De Santis M, Palou Redorta J, Nishiyama H, et al. Durvalumab in combination with BCG for BCG-naive, high-risk, non-muscle-invasive bladder cancer (POTOMAC): final analysis of a randomised, open-label, phase 3 trial. Lancet. 2025;406(10516):2221-2234. doi:10.1016/S0140-6736(25)01897-5 Larkin J, Powles TB, Frangou E, et al. First results from RAMPART: An international phase III randomised-controlled trial of adjuvant durvalumab monotherapy or combined with tremelimumab for resected primary renal cell carcinoma (RCC) led by MRC CTU at UCL. Ann Oncol. 2025;36(suppl 2):S1750. doi:10.1016/j.annonc.2025.09.110

In the latest episode of Oncology Decoded, hosts Manojkumar Bupathi, MD, MS, and Benjamin Garmezy, MD, broke down the treatment decision-making process for patients who present with oligometastatic kidney cancer. The experts zeroed in on this topic following their attendance at the 2025 International Kidney Cancer Symposium (IKCS), which featured a variety of sessions discussing the oligometastatic treatment setting.The conversation opened with an aim to better define what oligometastatic disease constitutes for patients. Bupathi noted how patients can present with synchronous, metachronous, or oligoprogressive cancer based on when metastases appear around the time of diagnosis. Furthermore, the specific nature of a patient’s metastases may influence their treatment course. For example, in the case of a patient with de novo metastatic clear cell disease and lung metastases, Bupathi recommended the use of systemic therapy followed by cytoreduction, and the possibility of nephrectomy plus stereotactic body radiotherapy directed to the metastases.Garmezy also emphasized distinguishing between de novo and recurrent disease, as both types necessitate the development of different treatment goals. For patients with recurrent oligometastatic disease, the primary goal of therapy may entail increasing the cure rate or extending treatment-free survival, depending on individual circumstances. Moreover, specific patient factors may influence the decision on whether to combine immunotherapy with radiotherapy.In terms of standardizing a therapeutic approach for patients who present with oligometastatic disease, the hosts stressed the importance of strengthening efforts across multidisciplinary clinics and collaborating with radiology colleagues to better identify which sites of metastasis are progressing in patients. Bupathi is an executive cochair of the Genitourinary Cancer Research Executive Committee at Sarah Cannon Research Institute (SCRI) and a medical oncologist with Rocky Mountain Cancer Centers, specializing in solid tumors and genitourinary cancers. Garmezy is the associate director of genitourinary research, an executive cochair of the Genitourinary Cancer Research Executive Committee at SCRI, and a medical oncologist at SCRI Oncology Partners specializing in genitourinary cancers.

Following the European Society for Medical Oncology (ESMO) Congress 2025, Oncology Decoded hosts Manojkumar Bupathi, MD, MS, and Benjamin Garmezy, MD, met to discuss the presentations and data sets that may have the biggest impacts across genitourinary (GU) cancer care. Bupathi is executive cochair of the Genitourinary Cancer Research Executive Committee at Sarah Cannon Research Institute (SCRI) and medical oncologist with Rocky Mountain Cancer Centers specializing in solid tumors and genitourinary cancers. Garmezy is associate director of genitourinary research and executive cochair of the Genitourinary Cancer Research Executive Committee at SCRI and medical oncologist at SCRI Oncology Partners specializing in genitourinary cancers. Bupathi and Garmezy outlined the top 5 abstracts from the meeting that have the potential to change or inform clinical practice across different GU malignancies. Notable presentations in bladder cancer, prostate cancer, kidney cancer, and other patient populations included the following: #5: Phase 3 CAPItello-281 Trial (NCT04493853) In the CAPItello-281 trial, combining capivasertib (Truqap) with abiraterone acetate, prednisone, and androgen deprivation therapy (ADT) prolonged radiographic progression-free survival (rPFS) among patients with PTEN-deficient de novo metastatic hormone-sensitive prostate cancer (HSPC).1 Data revealed a median rPFS of 33.2 months (95% CI, 25.9-44.2) in the capivasertib arm vs 25.7 months (95% CI, 22.0-29.9) in the placebo arm (HR, 0.81; 95% CI, 0.66-0.98; P = .034). #4: Phase 3 RC48-C016 Trial (NCT05302284) Combining disitamab vedotin (PF-08046051) with toripalimab-tpzi (Loqtorzi) in the frontline setting significantly improved outcomes vs standard chemotherapy among patients with HER2-expressing locally advanced or metastatic urothelial carcinoma, according to data from the RC48-C016 trial.2 Per blinded independent review committee (BIRC) assessment, the median PFS was 13.1 months (95% CI, 11.1-16.7) in the disitamab vedotin arm and 6.5 months (95% CI, 5.7-7.4) in the chemotherapy arm (HR, 0.36; 95% CI, 0.28-0.46; P <.0001). Additionally, the median overall survival (OS) was 31.5 months (95% CI, 21.7-not evaluable [NE]) vs 16.9 months (95% CI, 14.6-21.7) in each respective arm (HR, 0.54; 95% CI, 0.41-0.73; P <.0001). #3: Phase 3 RAMPART Trial (NCT03288532) Findings from the RAMPART trial showed that adjuvant therapy with durvalumab (Imfinzi) plus tremelimumab-actl (Imjudo) following renal cell carcinoma (RCC) resection improved disease-free survival (DFS) compared with active monitoring.3 The 3-year DFS rates were 81% in the durvalumab/tremelimumab arm vs 73% in the active monitoring arm across the intent-to-treat (ITT) population (HR, 0.65; 95% CI, 0.45-0.93; P = .0094). Additional data revealed that the DFS benefit associated with the durvalumab combination may have been driven by outcomes observed in the higher-risk population (HR, 0.52; 95% CI, 0.34-0.80; P = .0016). #2: Phase 3 PSMAddition Trial (NCT04720157) Lutetium Lu 177 vipivotide tetraxetan (Pluvicto) plus ADT and an androgen receptor pathway inhibitor (ARPI) demonstrated statistically significant improvements in rPFS among patients with prostate specific-membrane antigen (PSMA)–positive metastatic HSPC in the PSMAddition trial.4 Data showed improvements with the lutetium Lu 177 vipivotide tetraxetan regimen vs an ARPI plus ADT alone in terms of rPFS (HR, 0.72; 95% CI, 0.58-0.90; P = .002) and OS (HR, 0.84; 95% CI, 0.83-1.13; P = .125). #1: Phase 3 KEYNOTE-905/EV-303 Trial (NCT03924895) Findings from the KEYNOTE-905/EV-303 trial showed improvements in event-free survival (EFS) among patients with muscle-invasive bladder cancer (MIBC) who were not eligible for or refused cisplatin-based chemotherapy following treatment with perioperative enfortumab vedotin-ejfv (Padcev) plus pembrolizumab (Keytruda) with radical cystectomy and standard pelvic lymph node dissection.5 The median EFS was not reached (NR; 95% CI, 37.3-NR) in the enfortumab vedotin arm vs 15.7 months (95% CI, 10.3-20.5) in the control arm, in which patients underwent radical cystectomy and standard pelvic lymph node dissection followed by observation (HR, 0.40; 95% CI, 0.28-0.57; P <.0001). References Fizazi K, Clarke NW, De Santis M, et al. A phase III study of capivasertib (capi) + abiraterone (abi) vs placebo (pbo) + abi in patients (pts) with PTEN deficient de novo metastatic hormone-sensitive prostate cancer (mHSPC): CAPItello-281. Presented at European Society for Medical Oncology (ESMO) Congress 2025; October 17-21, 2025; Berlin, Germany. Abstract 2383O. Sheng X, Zeng G, Zhang C, et al. Disitamab vedotin (DV) plus toripalimab (T) versus chemotherapy (C) in first-line (1L) locally advanced or metastatic urothelial carcinoma (la/mUC) with HER2-expression. Presented at European Society for Medical Oncology (ESMO) Congress 2025; October 17-21, 2025; Berlin, Germany. Abstract LBA7. Larkin J, Powles TB, Frangou E, et al. First results from RAMPART: an international phase III randomised-controlled trial of adjuvant durvalumab monotherapy or combined with tremelimumab for resected primary renal cell carcinoma (RCC) led by MRC CTU at UCL. Presented at European Society for Medical Oncology (ESMO) Congress 2025; October 17-21, 2025; Berlin, Germany. Abstract LBA93. Tagawa ST, Sartor O, Piulats JM, et al. Phase III trial of [177Lu]Lu-PSMA-617 combined with ADT + ARPI in patients with PSMA-positive metastatic hormone-sensitive prostate cancer (PSMAddition). Presented at European Society for Medical Oncology (ESMO) Congress 2025; October 17-21, 2025; Berlin, Germany. Abstract LBA6. Vulsteke C, Kaimakliotis HZ, Danchaivijitr P, et al. Perioperative enfortumab vedotin plus pembrolizumab in participants with muscle-invasive bladder cancer who are cisplatin-ineligible: phase 3 KEYNOTE-905 study. Presented at European Society for Medical Oncology (ESMO) Congress 2025; October 17-21, 2025; Berlin, Germany. Abstract LBA2.

Ahead of the European Society for Medical Oncology Congress (ESMO) 2025, Oncology Decoded hosts Manojkumar Bupathi, MD, MS, and Benjamin Garmezy, MD, convened to discuss the late-breaking abstracts and presentations in genitourinary cancer management they anticipated the most. Bupathi is executive cochair of the Genitourinary Cancer Research Executive Committee at Sarah Cannon Research Institute (SCRI) and medical oncologist with Rocky Mountain Cancer Centers specializing in solid tumors and genitourinary cancers. Garmezy is associate director of genitourinary research and executive cochair of the Genitourinary Cancer Research Executive Committee at SCRI and medical oncologist at SCRI Oncology Partners specializing in genitourinary cancers.The hosts reviewed upcoming trial data that may shift therapeutic standards across bladder cancer, prostate cancer, kidney cancer, and other genitourinary malignancy populations. Presentations of interest included those on the following studies:- Phase 3 PSMAddition trial (NCT04720157)o Investigators assessed whether the addition of lutetium Lu 177 vipivotide tetraxetan (Pluvicto) to androgen deprivation (ADT) and androgen receptor pathway inhibitors (ARPIs) could improve radiographic progression-free survival (rPFS) vs standard of care alone in patients with metastatic hormone-sensitive prostate cancer.o Prior topline data showed a significant rPFS improvement in the lutetium Lu 177 arm.o Findings may support moving radioligand therapy to an earlier prostate cancer treatment setting.- Phase 3 KEYNOTE-905/EV-303 trial (NCT03924895)o Patients with muscle-invasive bladder cancer who were ineligible for cisplatin were assigned to receive surgery plus perioperative pembrolizumab (Keytruda) and enfortumab vedotin-ejfv (Padcev) or surgery alone.o According to previous topline results, statistically significant and clinically meaningful rPFS and overall survival (OS) improvements occurred in the enfortumab vedotin plus pembrolizumab arm.o Data may pose questions about the future role that chemotherapy may play in the perioperative space among patients with MIBC.-  Phase 3 RAMPART trial (NCT03288532)o  Investigators evaluated durvalumab (Imfinzi) with or without tremelimumab-actl (Imjudo) among patients with resected primary renal cell carcinoma.o If the data are positive, trials like RAMPART may clarify the role that immunotherapy can play in the perioperative treatment setting.  References An international prospective open-label, randomized, phase III study comparing 177Lu-PSMA-617 in combination with SoC, versus SoC alone, in adult male patients with mHSPC (PSMAddition). ClinicalTrials.gov. Updated September 23, 2025. Accessed October 15, 2025. https://tinyurl.com/ycbktner Novartis Pluvicto™ demonstrates statistically significant and clinically meaningful rPFS benefit in patients with PSMA-positive metastatic hormone-sensitive prostate cancer. News release. Novartis. June 2, 2025. Accessed October 14, 2025. https://tinyurl.com/fedzdhfx Perioperative pembrolizumab (MK-3475) plus cystectomy or perioperative pembrolizumab plus enfortumab vedotin plus cystectomy versus cystectomy alone in participants who are cisplatin-ineligible or decline cisplatin with muscle-invasive bladder cancer (MK-3475-905/​KEYNOTE-905/​EV-303). ClinicalTrials.gov. Updated August 28, 2025. Accessed October 15, 2025. https://tinyurl.com/5ddk6hrw PADCEV plus KEYTRUDA significantly improves survival for certain patients with bladder cancer when given before and after surgery. News release. Pfizer and Astellas Pharma. August 12, 2025. Accessed October 15, 2025. https://tinyurl.com/mtnvfvv2 Renal Adjuvant MultiPle Arm Randomised Trial (RAMPART). ClinicalTrials.gov. Updated September 7, 2020. Accessed October 15, 2025. https://tinyurl.com/26w8whuk

In this episode of Oncology Decoded, hosts Manojkumar Bupathi, MD, MS, and Benjamin Garmezy, MD, discussed the role that circulating tumor DNA (ctDNA) may play in the monitoring and management of genitourinary cancers as well as other disease types with their colleague, Arnab Basu, MBBS, MPH, FACP.The group began by providing an overview of ctDNA’s importance in the field, with Basu highlighting his initial use of the marker when treating patients with colorectal cancer who were experiencing toxicity in the adjuvant setting. Additionally, Basu distinguished between tumor-informed and tumor-uninformed testing, emphasizing an approach that monitors for actionable genes that can inform targeted decision-making from a therapeutic standpoint. Describing how the chance of a false positive is less than 1%, Basu stated that a positive result in the adjuvant setting almost certainly guarantees the need for therapy.As part of the discussion, the experts considered the utility of ctDNA based on prior findings from studies like the phase 3 NIAGARA trial (NCT03732677), in which higher ctDNA clearance from baseline to the time before radical cystectomy correlated with an enhanced benefit with the addition of durvalumab (Imfinzi) to neoadjuvant chemotherapy. Regarding the potential next steps in the field, the group spoke about the potential use of urine ctDNA testing in bladder cancer, the possibility of investigating the de-escalation of imaging, and the need for additional cross-comparison data on different mechanisms of ctDNA testing.Bupathi is executive cochair of the Genitourinary Cancer Research Executive Committee at Sarah Cannon Research Institute (SCRI) and medical oncologist with Rocky Mountain Cancer Centers specializing in solid tumors and genitourinary cancers. Garmezy is associate director of genitourinary research and executive cochair of the Genitourinary Cancer Research Executive Committee at SCRI and medical oncologist at SCRI Oncology Partners specializing in genitourinary cancers. Basu is the senior associate consultant and a medical oncologist specializing in the care of genitourinary cancers at Mayo Clinic Comprehensive Cance Center.ReferencePowles T, Van Der Heijden MS, Wang Y, et al. Circulating tumor DNA (ctDNA) in patients with muscle-invasive bladder cancer (MIBC) who received perioperative durvalumab (D) in NIAGARA. J Clin Oncol. 2025;43(suppl 16):4503. doi:10.1200/JCO.2025.43.16_suppl.4503

While attending the 2025 World Conference on Genitourinary Cancers (World GU), Oncology Decoded hosts Manojkumar Bupathi, MD, MS, and Benjamin Garmezy, MD, spoke with various experts and presenters about critical developments that may improve the treatment of patients with different genitourinary malignancies. Bupathi is executive cochair of the Genitourinary Cancer Research Executive Committee at Sarah Cannon Research Institute (SCRI) and medical oncologist with Rocky Mountain Cancer Centers specializing in solid tumors and genitourinary cancers. Garmezy is associate director of genitourinary research and executive cochair of the Genitourinary Cancer Research Executive Committee at SCRI and medical oncologist at SCRI Oncology Partners specializing in genitourinary cancers.In this episode, Bupathi and Garmezy explored the conference halls to chat with several colleagues and peers who presented on topics related to the care of those with prostate cancer, kidney cancer, bladder cancer, and other genitourinary malignancies. The hosts exchanged ideas on how to elevate the quality of care for these patients in a community-based setting with the following attendees:·      Mehmet Asim Bilen, MD, a professor in the Department of Hematology and Medical Oncology at Emory University School of Medicine and director of the Genitourinary Medical Oncology Program at Winship Cancer Institute of Emory University;·      Sid Sadler, a patient advocate and survivor of kidney cancer;·      Kerry R. Schaffer, MD, an assistant professor of Medicine in the Division of Hematology and Oncology of the Department of Medicine at Vanderbilt University Medical Center;·      Mark T. Fleming, MD, a board-certified medical oncologist at Virginia Oncology Associates;·      Jeff Yorio, MD, a medical oncologist who serves as the Central Texas Research Site Leader for Texas Oncology and SCRI;·      Mike Lattanzi, MD, a medical oncologist with a focus on genitourinary malignancies at Texas Oncology;·      Elizabeth Kessler, MD, an associate professor of Medical Oncology at the University of Colorado;·      Benjamin L. Maughan, MD, PharmD, an associate professor in the Division of Medical Oncology at Huntsman Cancer Institute;·      and Alan Tan, MD, a genitourinary oncology and melanoma specialist at Vanderbilt-Ingram Cancer Center as well as an assistant professor of Medicine in the Division of Hematology and Oncology at Vanderbilt University Medical Center.

Oncology Decoded hosts Manojkumar Bupathi, MD, MS, and Benjamin Garmezy, MD, traveled to the 2025 World Conference on Genitourinary Cancers (World GU) to speak with different experts about important advances and key takeaways related to the care of patients with genitourinary malignancies. Bupathi is executive cochair of the Genitourinary Cancer Research Executive Committee at Sarah Cannon Research Institute (SCRI) and medical oncologist with Rocky Mountain Cancer Centers specializing in solid tumors and genitourinary cancers. Garmezy is associate director of genitourinary research and executive cochair of the Genitourinary Cancer Research Executive Committee at SCRI and medical oncologist at SCRI Oncology Partners specializing in genitourinary cancers. In this episode, Bupathi and Garmezy sat down with Sam S. Chang MD, MBA, and Jeff Yorio, MD, to exchange knowledge on elevating the efficacy of multidisciplinary care for patients with prostate cancer, kidney cancer, and bladder cancer in a community-based setting. Chang is the chief surgical officer and the Urologic Oncology division chief at the Vanderbilt Ingram Cancer Center. Yorio is a medical oncologist who serves as the Central Texas Research Site Leader for Texas Oncology and SCRI. The conversation partly focused on overcoming challenges associated with prostate cancer management in a community practice. Chang highlighted strategies for risk stratifying disease based on previously published guidelines, noting the importance of surveillance depending on a patient’s observed degree of risk. Additionally, the experts discussed how factors such as Decipher® Prostate scores, MRI scans, and prostate-specific antigen (PSA) levels may factor into the decision to surveil patients with prostate cancer.  Regarding kidney cancer, the group spoke about strategies for deciding between monitoring patients or expediting intervention with modalities like nephrectomy or cryoablation. An observed mass of less than 2 cm, for example, represented a situation where surveillance could be optimal. The experts also detailed appropriate circumstances for offering immunotherapy and tyrosine kinase inhibitor (TKI)–based regimens upfront prior to surgery. As part of the discussion on bladder cancer management, the group emphasized improving systemic therapies and locally assessing the bladder more efficiently. Additionally, with a newfound “embarrassment of riches and possibilities” regarding the development and approval of novel intravesical therapies, the experts discussed how medical oncologists can best collaborate with urologists to monitor patients undergoing this type of treatment.

In this episode of Oncology Decoded, hosts Manojkumar Bupathi, MD, MS, and Benjamin Garmezy, MD, traveled to the 2025 World Conference on Genitourinary Cancers (World GU) to speak with various experts about key advances in genitourinary oncology. As part of one discussion, Bupathi and Garmezy sat down with Bradley G. Somer, MD, to exchange ideas about the management of genitourinary cancers harboring variant histologies, which included such populations as those with prostate cancer, bladder cancer, and kidney cancer.Regarding prostate cancer, the group highlighted potential treatment strategies for patient subgroups such as those with small cell histology or neuroendocrine differentiation. The discussion explored how modalities such as androgen deprivation therapy, chemotherapy, and radiation may factor into the care of patients with prostate cancer harboring variant histologies, especially in the context of a community oncology setting.Next, the conversation focused on methods for managing papillary, plasmacytoid, small cell, and other disease variants in the context of bladder cancer. Based on previously published data and prior clinical experience, the group discussed the appropriate circumstances for implementing regimens such as enfortumab vedotin-ejfv (Padcev) plus pembrolizumab (Keytruda) or other immunotherapy approaches depending on how a patient presents with bladder cancer.Additionally, the group reviewed strategies for managing clear cell, papillary, and chromophobe variants in kidney cancer along with other disease histologies. The experts considered key factors for deciding on when to administer VEGF inhibitors and other tyrosine kinase inhibitor combinations based on the observed histology.Bupathi is executive cochair of the Genitourinary Cancer Research Executive Committee at Sarah Cannon Research Institute (SCRI) and medical oncologist with Rocky Mountain Cancer Centers specializing in solid tumors and genitourinary cancers. Garmezy is associate director of genitourinary research and executive cochair of the Genitourinary Cancer Research Executive Committee at SCRI and medical oncologist at SCRI Oncology Partners specializing in genitourinary cancers. Somer is a medical oncologist, senior partner on the Executive Cancer Council, and president at West Cancer Center & Research Institute.

In this episode of Oncology Decoded, hosts Manojkumar Bupathi, MD, MS, and Benjamin Garmezy, MD, spoke with Nabil Adra, MD, about testicular cancer care. The discussion gave a comprehensive overview of managing germ cell tumors, offering practical pearls for community oncologists.The conversation opened with the initial approach to a patient presenting with a testicular mass. The doctors emphasize the importance of a thorough workup, including a CT scan of the chest, abdomen, and pelvis, and the use of tumor markers: AFP and hCG. Adra noted that while AFP and hCG are elevated in about 60% of cases, it’s crucial to understand their half-lives—about 5 to 7 days for AFP and 1 to 2 days for hCG—to properly assess their decline post-orchiectomy. He clarified that an AFP level under 25 ng/mL is considered normal and that mild elevations in hCG can be linked to marijuana use or cross-reactivity with luteinizing hormone, which should be investigated before initiating chemotherapy. The panel also touches on the use of lactate dehydrogenase as a prognostic marker, cautioning against using it as the sole basis for starting treatment.A central part of the discussion revolves around the bleomycin, etoposide, cisplatin (BEP) vs etoposide and cisplatin chemotherapy regimens for good-risk disease. Adra explained the rationale behind the preference for BEP for 3 cycles at his institution, arguing that it avoids the long-term toxicities of neuropathy and ototoxicity associated with a fourth cycle of platinum therapy, a concern with the EP for 4 cycles. He stressed that with careful patient selection—avoiding bleomycin in patients over 50, with renal dysfunction, or pre-existing lung disease—the risk of pulmonary toxicity is minimal. He also influenced Garmezy’s practice by highlighting the importance of monitoring tumor markers with every cycle of chemotherapy, noting that a rising marker could signal a need to pivot to second-line therapy.The conversation shifted to the role of surgery in stage II disease. For patients with non-bulky (less than 3 cm) stage II seminoma or non-seminoma, the panel discusses the preference for a retroperitoneal lymph node dissection (RPLND) over upfront chemotherapy or radiation to spare patients from long-term side effects. Adra highlighted that a proper RPLND at an experienced center can be curative in 80% of cases. The doctors stressed the importance of referring patients to surgeons with extensive experience in these complex procedures.Finally, the hosts and guest tackled the management of relapsed/refractory disease. They discussed the 3 main options: salvage surgery, standard-dose chemotherapy, or high-dose chemotherapy with stem cell transplant. Adra shared that his institutional preference is for high-dose chemotherapy due to published data showing high cure rates, mentioning the ongoing phase 3 TIGER trial (NCT02375204), which is directly comparing standard-dose paclitaxel, ifosfamide, and cisplatin with high-dose chemotherapy. The episode concluded with a key pearl on managing patients with a high burden of pulmonary metastases, where a "cycle 0" of EP is sometimes used before starting a full course of vinblastine, ifosfamide, and cisplatin to mitigate the risk of hemoptysis.Bupathi, is executive cochair of the Genitourinary Cancer Research Executive Committee at Sarah Cannon Research Institute (SCRI) and medical oncologist with Rocky Mountain Cancer Centers specializing in solid tumors and genitourinary cancers; Garmezy, is associate director of genitourinary research and executive cochair of the Genitourinary Cancer Research Executive Committee at SCRI and medical oncologist at SCRI Oncology Partners specializing in genitourinary cancers, and Adra is associate professor of Clinical Medicine and Clinical Urology, service line leader in medical oncology, medical director of Indiana University Health Simon Cancer Center, and program leader-genitourinary. 

The latest Oncology Decoded discussion with Manojkumar Bupathi, MD, MS, executive cochair of the Genitourinary Cancer Research Executive Committee at Sarah Cannon Research Institute (SCRI) and medical oncologist with Rocky Mountain Cancer Centers specializing in solid tumors and genitourinary cancers, and Benjamin Garmezy, MD, associate director of genitourinary research and executive cochair of the Genitourinary Cancer Research Executive Committee at SCRI and medical oncologist at SCRI Oncology Partners specializing in genitourinary cancers, dissects the current management of metastatic urothelial carcinoma, with a focus on treatment strategies beyond standard first-line therapies. The conversation highlights the recent paradigm shift with the approval of enfortumab vedotin-ejfv (Padcev) in combination with pembrolizumab (Keytruda). This combination’s efficacy, as demonstrated in the phase 3 EV-302 trial (NCT04223856), has positioned it as a new standard of care for many patients. The alternative, gemcitabine plus cisplatin with nivolumab (Opdivo), supported by the phase 3 CheckMate 901 trial (NCT03036098), remains a crucial first-line option, particularly for patients who are cisplatin-eligible.The hosts delve into the nuances of second-line therapy, which has become a more complex and critical area. For patients who progress on enfortumab vedotin/pembrolizumab, the discussion covers options such as platinum-based chemotherapy with gemcitabine/cisplatin or carboplatin. The importance of biomarker-driven therapy is also emphasized, particularly the role of molecular testing for FGFR gene alterations. The FDA-approved FGFR inhibitor erdafitinib (Balversa) is highlighted as a viable option for patients with susceptible genetic alterations. Furthermore, the discussion touches on the evolving role of HER2-targeted agents and other novel early-phase assets that are being developed to address the unmet need in this patient population.Management of toxicities is also a significant theme. The clinicians share insights on mitigating adverse effects such as peripheral neuropathy from enfortumab vedotin, and the challenges of managing hyperglycemia and skin toxicities. The need for more data-driven guidance on treatment duration and maintenance therapy is also underscored, with the observation that treatment discontinuation is a common clinical challenge lacking clear guidelines.ReferenceFDA approves enfortumab vedotin-ejfv with pembrolizumab for locally advanced or metastatic urothelial cancer. News release. FDA. December 15, 2023. Accessed August 13, 2025. https://tinyurl.com/45wkm3bd

This episode of Oncology Decoded focuses on a discussion between hosts Manojkumar Bupathi, MD, MS, executive cochair of the Genitourinary Cancer Research Executive Committee at Sarah Cannon Research Institute (SCRI) and medical oncologist with Rocky Mountain Cancer Centers specializing in solid tumors and genitourinary cancers, and Benjamin Garmezy, MD, associate director of genitourinary research and executive cochair of the Genitourinary Cancer Research Executive Committee at SCRI and medical oncologist at SCRI Oncology Partners specializing in genitourinary cancers, in a recent live session with US Oncology Network and the Pathways Task Force, discussing the evolving landscape of second-line and beyond therapy for urothelial carcinoma, particularly in the context of recent advancements in first-line treatment.First Line StrategiesThe current standard of care for frontline metastatic urothelial carcinoma is enfortumab vedotin-ejfv (Padcev) in combination with pembrolizumab (Keytruda). Recent data from the phase EV-302 trial (NCT04223856) presented at the 2025 American Society of Clinical Oncology (ASCO) highlighted the remarkable durability of responses with this combination, showing a 2-year durability in a significant proportion of responders, including 75% of complete responders.1 While this combination is favored for most patients, the hosts acknowledged a subgroup for whom it may not be suitable due to unique toxicities such as neuropathy, skin toxicity, and hyperglycemia. The phase 3 Checkmate901 trial (NCT03036098), evaluating cisplatin/gemcitabine with nivolumab (Opdivo), is also mentioned as a prior standard of care, though generally superseded by enfortumab vedotin/pembrolizumab. For patients with lymph-node-only disease, both cisplatin/gemcitabine and nivolumab or enfortumab vedotin/pembrolizumab show comparable high response rates, necessitating shared decision-making.Second Line StrategiesFor patients progressing on enfortumab vedotin/pembrolizumab, the subsequent treatment landscape becomes more complex. Platinum-based chemotherapy doublets (cisplatin/gemcitabine or carboplatin/gemcitabine) are considered, though their efficacy in this heavily pretreated setting is limited and associated with significant toxicity.Molecular testing for FGFR alterations is crucial, as erdafitinib (Balversa) offers a targeted option with a 40% response rate in patients who are FGFR-positive. Managing erdafitinib toxicities, including nail changes, skin reactions, and phosphate level elevations, requires close monitoring and patient education. The potential role of HER2-targeted antibody-drug conjugates is also discussed, particularly for HER2 3+ expression, though data in urothelial carcinoma are limited.For patients without actionable biomarkers, single-agent taxanes (docetaxel, paclitaxel) have historically shown dismal response rates (~15-17%). Sacituzumab govitecan-hziy (Trodelvy), despite its accelerated approval withdrawal due to the confirmatory phase 2 TROPHY-U-01 trial (NCT03547973) not meeting statistical significance against single-agent chemotherapy, is still utilized by the speakers. They emphasize that with appropriate growth factor support, sacituzumab govitecan can be less toxic and equally efficacious as carboplatin/gemcitabine in select patients.References1.        Bedke J, Powles TB, Valderrama BP, et al. EV-302: long-term subgroup analysis from the phase 3 global study of enfortumab vedotin in combination with pembrolizumab (EV+P) vs chemotherapy (chemo) in previously untreated locally advanced or metastatic urothelial carcinoma (la/mUC). J Clin Oncol. 2025;43(suppl 16):4571. doi:10.1200/JCO.2025.43.16_suppl.45712.        Van der Heijden M, Galsky M, Powles T, et al. Nivolumab plus ipilimumab (NIVO+IPI) vs gemcitabine-carboplatin (gem-carbo) chemotherapy for previously untreated unresectable or metastatic urothelial carcinoma (mUC): Final results for cisplatin-ineligible patients from the CheckMate 901 trial. J Clin Oncol. 2025;43(suppl 17):4500. doi:10.1200/JCO.2025.43.16_suppl.45003.        Gilead provides update on U.S. Indication for Trodelvy in metastatic urothelial cancer. News release. Gilead Sciences, Inc. October 18, 2024. Accessed July 30, 2025. https://tinyurl.com/2aku377j

The Oncology Decoded podcast, co-hosted by Manojkumar Bupathi, MD, MS, executive cochair of the Genitourinary Cancer Research Executive Committee at Sarah Cannon Research Institute (SCRI) and medical oncologist with Rocky Mountain Cancer Centers specializing in solid tumors and genitourinary cancers, and Benjamin Garmezy, MD, associate director of genitourinary research and executive cochair of the Genitourinary Cancer Research Executive Committee at SCRI and medical oncologist at SCRI Oncology Partners specializing in genitourinary cancers, in a recent live session with US Oncology Network and the Pathways Task Force, delved into significant updates that were set to happen at the 2025 American Society of Clinical Oncology (ASCO), focusing on the genitourinary cancer landscape.Bupathi and Garmezy were joined by John M. Burke, MD, a hematologist and medical oncologist at Rocky Mountain Cancer Centers, and Dhaval R. Shah, MBBS, a medical oncologist from Christiana Care. A primary focus of the discussion was the phase 3 KEYNOTE-564 trial (NCT03142334), a pivotal trial for patients with renal cell carcinoma (RCC). This study investigated pembrolizumab (Keytruda) as adjuvant therapy for patients with clear cell RCC who had undergone surgical resection and presented with intermediate-high or high-risk features. Garmezy highlighted the "clear separation of the curves" in disease-free survival (DFS), with an HR of 0.68, and a compelling 5% difference in long-term overall survival, signifying a benefit for "about 1 in 20 patients". Despite about 20% of patients discontinuing treatment due to toxicity, the overall safety profile of pembrolizumab was considered well-tolerated, with no statistically significant difference in quality of life compared with placebo.Burke provided the panel with his perspective on evaluating such trials. He emphasized the importance of scrutinizing study design flaws, even in "randomized, double-blind, placebo-controlled, phase 3 clinical trials," which are often seen as the "epitome of great science". Key questions for consideration include the appropriateness of the control arm (placebo in KEYNOTE-564 was deemed appropriate), the validity of surrogate end points like DFS, and the presence of "informative censoring"—a form of bias that can skew results. Burke noted that informative censoring can occur if patients drop out of a trial due to disappointment with their randomized arm or due to drug toxicity, which can make the treatment arm's progression-free survival look better than it truly is.The discussion also touched upon the consistency of KEYNOTE-564’s findings with other trials. Garmezy noted that while pembrolizumab showed positive results, other adjuvant studies involving atezolizumab (Tecentriq), nivolumab (Opdivo), and nivolumab plus ipilimumab (Yervoy) had no significant difference, potentially due to differences in drug type or duration of therapy (6 vs 12 months). Shah affirmed that despite these nuances, the overall survival benefit seen in KEYNOTE-564 justifies the use of adjuvant pembrolizumab for eligible patients, emphasizing adherence to the exact trial criteria.Beyond kidney cancer, the podcast previewed discussions on the phase 3 NIAGARA trial (NCT03732677) for perioperative bladder cancer and the phase 3 TALAPRO-2 trial (NCT03395197) for first-line metastatic castrate-resistant prostate cancer (mCRPC). Bupathi highlighted the ongoing debate within the Pathways Committees regarding the integration of new data vs established practices, particularly concerning the timeline for new drugs to be incorporated into pathways. Burke clarified that while Pathways guides value-driven decisions, physicians retain the autonomy to prescribe off-pathway regimens, though financial implications might arise. The episode concluded with a look ahead to more data releases, underscoring the dynamic nature of oncology practice and the continuous evaluation of therapies for optimal patient care.ReferenceChoueiri TK, Tomczak P, Park SH, et al; KEYNOTE-564 Investigators. Overall survival with adjuvant pembrolizumab in renal-cell carcinoma. N Engl J Med. 2024;390(15):1359-1371. doi:10.1056/NEJMoa2312695

As part of the latest Oncology Decoded discussion, Manojkumar Bupathi, MD, MS, met with Benjamin Garmezy, MD, after the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting to review data from the late-breaking abstracts, poster sessions, and other presentations of interest that may shift the paradigm across different genitourinary malignancies.Bupathi is the executive cochair of the Genitourinary Cancer Research Executive Committee at Sarah Cannon Research Institute (SCRI) and medical oncologist with Rocky Mountain Cancer Centers specializing in solid tumors and genitourinary cancers. Garmezy is the associate director of genitourinary research and executive cochair of the Genitourinary Cancer Research Executive Committee at SCRI and medical oncologist at SCRI Oncology Partners, also specializing in genitourinary cancers. These experts highlighted their top abstracts and presentations from this year’s ASCO Annual Meeting, breaking down the results and clinical implications of key research in prostate cancer, bladder cancer, and other patient populations. Noteworthy studies and analyses included the following:·      Phase 3 AMPLITUDE Trial (NCT04497844)o   Niraparib (Zejula) plus abiraterone acetate (Zytiga) with prednisone (AAP) reached the primary end point of radiographic progression-free survival (rPFS), reducing the risk of radiographic progression or death by 48% (HR, 0.52; 95% CI, 0.37-0.72; P <.0001) in the BRCA-mutated metastatic castration-sensitive prostate cancer (CSPC) population and 37% (HR, 0.63; 95% CI, 0.49-0.80; P = .0001) in the homologous recombination repair (HRR)–mutated subgroup vs AAP alone.o   The niraparib combination also improved time to symptomatic progression across the BRCA-mutant population (HR, 0.44; 95% CI, 0.29-0.68; P = .0001) and the HRR-mutant subgroup (HR, 0.50; 95% CI, 0.36-0.69; P <.0001).o   Overall, data from AMPLITUDE appear to support early genomic testing and reinforce niraparib plus AAP as a new therapeutic option for patients with metastatic CSPC harboring HRR alterations.·      Phase 3 NIAGARA Trial (NCT03732677)o   Investigators found circulating tumor DNA (ctDNA) status to be highly prognostic for outcomes among patients who received perioperative durvalumab (Imfinzi) plus neoadjuvant chemotherapy for muscle-invasive bladder cancer (MIBC).o   Across the treatment arms in the NIAGARA trial, ctDNA-negative status conferred improvements in event-free survival (EFS) vs ctDNA positivity (HR, 0.42; 95% CI, 0.30-0.60).o   Adding nivolumab to neoadjuvant chemotherapy increased the rate of ctDNA clearance by 13% vs the use of chemotherapy alone.·      Phase 2 SURE-02 Trial (NCT05535218)o   Combining perioperative sacituzumab govitecan-hziy (Trodelvy) with pembrolizumab (Keytruda) produced clinical complete responses in 44.4% (95% CI, 27.9%-61.9%) of patients with MIBC.o   The study treatment allowed for bladder preservation without chemoradiotherapy in 74% of patients who refused radical cystectomy.o   The data demonstrated a potentially safe and effective approach for patients with no standard-of-care options at the time of refusing radical cystectomy.References1. Attard G, Agarwal N, Graff J, et al. Phase 3 AMPLITUDE trial: niraparib (NIRA) and abiraterone acetate plus prednisone (AAP) for metastatic castration-sensitive prostate cancer (mCSPC) patients (pts) with alterations in homologous recombination repair (HRR) genes. J Clin Oncol. 2025;43(suppl 17):LBA5006. doi:10.1200/JCO.2025.43.17_suppl.LBA50062. Powles T, Van Der Heijden M, Wang Y, et al. Circulating tumor DNA (ctDNA) in patients with muscle-invasive bladder cancer (MIBC) who received perioperative durvalumab (D) in NIAGARA. J Clin Oncol. 2025;43(suppl 16):4503.doi:10.1200/JCO.2025.43.16_suppl.45033. Necchi A, de Jong J, Proudfoot J, et al. First results of SURE-02: A phase 2 study of neoadjuvant sacituzumab govitecan (SG) plus pembrolizumab (pembro), followed by response-adapted bladder sparing and adjuvant pembro, in patients with muscle-invasive bladder cancer (MIBC). J Clin Oncol. 2025;43(suppl 16):4518. doi:10.1200/JCO.2025.43.16_suppl.4518

Experts weigh in on the practical applications of PSMA PET imaging, risk stratification, and evolving treatment strategies for advanced prostate cancer.  Biochemical recurrence can be a clinical tightrope walk. The latest Oncology Decoded episode highlights prostate-specific membrane antigen (PSMA) PET imaging, offering a practical, expert-led exploration of how this advanced modality is moving beyond theoretical benefits to become a cornerstone in the management of advanced prostate cancer.   The panel included:  Manojkumar Bupathi, MD, MS, executive cochair of the Genitourinary Cancer Research Executive Committee at Sarah Cannon Research Institute (SCRI) and medical oncologist with Rocky Mountain Cancer Centers specializing in solid tumors and genitourinary cancers;  Benjamin Garmezy, MD, associate director of genitourinary research and executive cochair of the Genitourinary Cancer Research Executive Committee at SCRI and medical oncologist at SCRI Oncology Partners specializing in genitourinary cancers, underscored the curative potential of adjuvant therapy in kidney cancer;   Mike Lattanzi, MD, a genitourinary medical oncologist from Texas Oncology;   Damian N. Sorce, MD, a urologist from Colorado Urology.   A key theme throughout the episode was the practical application of PSMA PET scans. The panelists share their experiences and insights on how PSMA imaging is impacting risk stratification in patients with prostate cancer. They discuss its role in identifying early metastatic disease, particularly in the context of biochemical recurrence after primary treatment. The ability of PSMA PET to detect bone lesions and lymph node involvement with greater sensitivity and specificity compared with conventional imaging is highlighted as a significant advantage in guiding treatment decisions.  The conversation touches upon the integration of PSMA imaging with established treatment modalities, such as androgen deprivation therapy (ADT) and radiation therapy. The experts discuss how PSMA findings can influence the timing and extent of these treatments, potentially leading to more personalized and effective approaches. For instance, the identification of oligometastatic disease through PSMA PET may guide the use of targeted therapies like stereotactic body radiation therapy (SBRT) in conjunction with systemic therapies.  Risk stratification emerges as a crucial aspect of utilizing PSMA imaging effectively. The panelists discuss how PSMA results can help differentiate between patients with localized recurrence amenable to salvage therapy and those with more widespread disease requiring systemic intervention. This improved risk assessment allows clinicians to tailor treatment strategies, potentially avoiding overtreatment in some cases and ensuring timely and aggressive therapy in others.  The importance of a multidisciplinary care team is implicitly underscored throughout the discussion. The interaction between urologists and oncologists, as represented by the panelists, highlights the need for seamless collaboration in interpreting PSMA imaging results and formulating comprehensive treatment plans for patients with advanced prostate cancer. 

In this special episode of Oncology Decoded, hosts Manojkumar Bupathi, MD, MS, and Benjamin Garmezy, MD, discussed the highly anticipated 2025 American Society of Clinical Oncology (ASCO) Annual Meeting. Bupathi is the executive cochair of the Genitourinary Cancer Research Executive Committee at Sarah Cannon Research Institute (SCRI) and medical oncologist with Rocky Mountain Cancer Centers specializing in solid tumors and genitourinary cancers, and Garmezy is the associate director of genitourinary research and executive cochair of the Genitourinary Cancer Research Executive Committee at SCRI and medical oncologist at SCRI Oncology Partners specializing in genitourinary cancers, underscored the curative potential of adjuvant therapy in kidney cancer.During the discussion, the experts highlight the abstracts that have caught their eye and offer their predictions on the data that could reshape the landscape of genitourinary oncology.Kidney CancerSeveral intriguing abstracts are highlighted, with a focus on the evolving role of immunotherapy and the potential for novel combinations. ·      Phase 3 PDIGREE trial (NCT03793166): Immunotherapy plus nivolumab (Opdivo) and ipilimumab (Yervoy) followed by nivolumab alone or nivolumab with cabozantinib (Cabometyx) for patients with advanced kidney cancer. This will be presented by Tian Zhang, MD, MHS, on May 31 from 1:27-1:33 pm CDT.·      Phase 1b STELLAR-002 trial (NCT05176483): Zanzalintinib plus nivolumab and relatlimab in patients with advanced solid tumors. This will be presented by Benjamin Garmezy, MD, in a poster presentation on June 2 at 2:30 pm CDT. The Bupathi and Garmezy suggest we should be on the lookout for data that could refine treatment algorithms and identify new biomarkers to guide therapy selection.Bladder CancerThe potential impact of neoadjuvant therapy and the role of circulating tumor DNA (ctDNA) analysis were key discussion points. The experts anticipated seeing updates from ongoing trials exploring the utility of ctDNA as a predictive and prognostic biomarker, potentially allowing for more personalized treatment approaches. ·      Phase 3 NIAGARA trial (NCT03732677): ctDNA will be assessed in those who received perioperative durvalumab (Imfinzi) for muscle-invasive bladder cancer. This will be presented by Thomas Pwles, MD, PhD, FCRP, on June 1 from 10:45-10:57 am CDT.·      Phase 3 Checkmate901 (NCT03036098): Nivolumab plus ipilimumab vs gemcitabine/carboplatin in patients who are previously untreated with unresectable or metastatic urothelial carcinoma. This will be presented by Michael Simon Van Der Heijden, MD, PhD, on June 1 from 9:45-9:57 am CDT. Prostate Cancer A significant portion of the discussion revolves around prostate cancer, with several potentially practice-changing abstracts generating excitement. ·      Artificial intelligence (AI): The use of a multimodal AI model to determine the benefit from a second-generation androgen receptor pathway inhibitor for patients who are high-risk and have non-metastatic prostate cancer and were enrolled on the phase 2/3 STAMPEDE trial (NCT00268476). This will be presented by Nicholas David James, PhD, FRCP, MBBS, on June 3 from 9:57-10:09 am CDT. ·      Radiation therapy: A phase 3 trial assessing CAN-2409 plus prodrug and standard of care external beam radiation therapy in patients with newly diagnosed localized prostate cancer. This will be presented by Theodore L. De-Weese, MD, on June 3 from 9:45-9:57 am CDT. Furthermore, the conversation touched upon anticipated phase 3 data in hormone-sensitive prostate cancer. Specifically, there’s excitement around upcoming results for patients with high-risk or high-volume metastatic hormone-sensitive prostate cancer harboring BRCA mutations. This data could be practice-changing and offer a new therapeutic avenue for this specific subset of patients.Beyond these specific disease areas, the podcast highlighted the broader themes expected at 2025 ASCO, including the continued development and refinement of immunotherapy, the integration of multimodal AI in oncology, and the ongoing investigation of novel targets, like TROP2 inhibitors. 

Manojkumar Bupathi, MD, MS; and Benjamin Garmezy, MD, dove into the complexities of adjuvant therapy for kidney cancer, providing valuable insights for oncology clinicians in the latest episode of Oncology Decoded. The discussion began with a fundamental overview of adjuvant therapy, which aims to eradicate residual microscopic disease and mitigate the risk of cancer recurrence.   Bupathi, executive cochair of the Genitourinary Cancer Research Executive Committee at Sarah Cannon Research Institute (SCRI) and medical oncologist with Rocky Mountain Cancer Centers specializing in solid tumors and genitourinary cancers, and Garmezy, associate director of genitourinary research and executive cochair of the Genitourinary Cancer Research Executive Committee at SCRI  and medical oncologist at SCRI Oncology Partners specializing in genitourinary cancers, underscored the curative potential of adjuvant therapy in kidney cancer. The discussion also focused on 2 primary modalities of adjuvant therapy: targeted therapies and immunotherapy. Targeted therapies, particularly VEGF tyrosine kinase inhibitors, were discussed in the context of clear cell kidney cancer, the predominant subtype, where they inhibit the VEGF signaling pathway to impede cancer cell growth. Bupathi and Garmezy spoke about results from the phase 3 KEYNOTE-564 trial (NCT03142334), which led to the FDA approval of pembrolizumab (Keytruda) for high-risk clear cell kidney cancer.1,2 The positive results from this trial are superior to those from others that explored different immunotherapy agents and regimens, none of which demonstrated a similar benefit. It was noted that there are differences in interpretations, heterogeneity in study designs, and patient populations for each trial. Regarding risk stratification in the postnephrectomy setting, the hosts gave a critical evaluation of the role of nomograms in predicting recurrence. The benefits of adjuvant therapy against the potential for treatment-related toxicities were weighed, with an emphasis on the importance of individualized patient counseling.   Finally, they highlighted the management of disease progression following adjuvant pembrolizumab, with a focus on treatment sequencing and the role of second-line therapies. The relevance of extrapolating data from metastatic trials to the adjuvant setting was discussed, with a pragmatic approach to clinical decision-making.   References1.        Choueiri TK, Tomczak P, Park SH, et al; KEYNOTE-564 Investigators. Overall survival with adjuvant pembrolizumab in renal-cell carcinoma. N Engl J Med. 2024;390(15):1359-1371. doi:10.1056/NEJMoa23126952.         FDA approves pembrolizumab for adjuvant treatment of renal cell carcinoma. News release. FDA. November 17, 2021. Accessed April 24, 2025. https://tinyurl.com/yzxcjetz

In the most recent episode of Oncology Decoded, co-hosts Manojkumar Bupathi, MD, MS, executive co-chair of Genitourinary Cancer Research Executive Committee at Sarah Cannon Research Institute and medical oncologist with Rocky Mountain Cancer Centers specializing in solid tumors and genitourinary cancers; and Benjamin Garmezy, MD, associate director of Genitourinary Research and executive co-chair of Genitourinary Cancer Research Executive Committee at Sarah Cannon Research Institute (SCRI) and medical oncologist at SCRI Oncology Partners specializing in genitourinary cancers, engaged in a detailed discussion focused on adjuvant therapy for kidney cancer, providing key insights regarding available treatment options.    The discussion began with defining adjuvant therapy that aims to improve disease-free survival, overall survival, or both. The hosts explore effective ways to communicate the goals and potential benefits of adjuvant therapy to patients, acknowledging the challenge of recommending treatment to patients who may feel they are already “cured” after surgery.    The conversation transitioned to the specifics of adjuvant therapy in renal cell carcinoma (RCC), with a focus on clear cell RCC.  Bupathi and Garmezy discussed the evolution of treatment strategies from VEGF tyrosine kinase inhibitors (TKIs) to immunotherapy.  They highlighted the significance of the phase 3 KEYNOTE-564 trial (NCT03142334), which supported the approval of adjuvant pembrolizumab (Keytruda), a PD-1 inhibitor, for certain patients who are high-risk. Additionally, they highlighted other immunotherapy trials and the distinction between PD-1 and PD-L1 inhibitors.    The discussion also touched upon patient selection for adjuvant pembrolizumab, with the hosts sharing their individual approaches. Factors influencing treatment decisions include disease stage, risk of recurrence, patient comorbidities, and potential treatment toxicities.  The importance of shared decision-making with patients is emphasized, particularly regarding the balance between potential benefits and risks of treatment.    Finally, practical guidance on managing treatment-related toxicities, including strategies for monitoring patients and addressing potential adverse effects, was mentioned. They also discuss the complexities of monitoring patients’ post-treatment, including the use of CT scans and the management of pulmonary nodules. The discussion extends to managing progressive disease in patients who have received adjuvant therapy, including the role of VEGF TKIs and clinical trials.    

This episode of Oncology Decoded tackled the challenging landscape of non-clear cell renal cell carcinoma (nccRCC), a heterogeneous group of tumors representing about 20% to 25% of all kidney cancers. The episode provided expert insights into the diagnosis and management of this complex disease. Meet the panel discussants:  Manojkumar Bupathi, MD, MS, executive co-chair of Genitourinary Cancer Research Executive Committee at Sarah Cannon Research Institute; medical oncologist with Rocky Mountain Cancer Centers specializing in solid tumors and genitourinary cancers; Benjamin Garmezy, MD, associate director of Genitourinary Research and executive co-chair of Genitourinary Cancer Research Executive Committee at Sarah Cannon Research Institute (SCRI); medical oncologist at SCRI Oncology Partners specializing in genitourinary cancers; Stephanie A. Berg, DO, medical oncologist for the Lank Center of Genitourinary Oncology at Dana-Farber Cancer Institute. The conversation centered around a case presentation: a 63-year-old female with papillary RCC, presenting with significant weight loss, cough, a large renal mass, and multiple pulmonary and bone metastases.The panel emphasized the importance of accurate pathological diagnosis, highlighting the diverse subtypes within nccRCC, including papillary, chromophobe, translocation, and collecting duct carcinomas. They acknowledged the limitations of historical treatment approaches, which have yielded suboptimal response rates and progression-free survival (PFS).The discussion then delved into the evolving treatment landscape, focusing on recent clinical trial data. The phase 2 PAPMET trial (NCT02761057) of cabozantinib (Cabometyx) vs sunitinib (Sutent) in patients with advanced RCC. The emergence of newer VEGF-selective TKIs, such as tivozanib (Fotivda), also showed promise in disease control.The panel highlighted the growing role of immunotherapy (IO) in nccRCC, particularly the combination of cabozantinib and nivolumab (Opdivo), which showed encouraging response rates in non-chromophobe subtypes. Similarly, the combination of lenvatinib and pembrolizumab demonstrated significant PFS and overall response rates across various nccRCC subtypes, including chromophobe.In the absence of clinical trials, the panel recommended a personalized approach to treatment, considering the patient's subtype, disease burden, and comorbidities. They generally favored IO-TKI combinations, such as lenvatinib plus pembrolizumab, for most patients with nccRCC, while acknowledging the potential role of ipilimumab (Yervoy) plus nivolumab (Opdivo) in select cases, particularly those with chromophobe histology and low disease burden.The panel also addressed the role of radiation therapy in nccRCC, particularly for oligometastatic disease and oligoprogressive disease. They emphasized the importance of multidisciplinary collaboration with radiation oncologists to optimize treatment strategies.Regarding molecular testing, the panel acknowledged its limited role in guiding treatment decisions at present but highlighted its potential to identify patients with specific genetic alterations, such as MET amplification or FH deficiency, who may benefit from targeted therapies or germline testing.Finally, challenges of sequencing therapies in nccRCC were discussed, emphasizing the lack of definitive data and the need for individualized treatment decisions. They generally favored sequencing TKIs, such as tivozanib or sunitinib, after progression on IO-TKI combinations, but acknowledged the need for further research to optimize treatment sequencing.Reference Tripathi A, Tangen C, Li X, et al. Pathologic concordance rate and outcomes by histologic subtype in advanced papillary renal cell (pRCC) carcinoma: An analysis from the SWOG S1500 (PAPMET) trial. J Clin Oncol. 2023;41(suppl 16):4562. doi:10.1200/JCO.2023.41.16_suppl.4562Physicians’ Education Resource®, LLC, is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for physicians.Physicians’ Education Resource®, LLC, designates this enduring material for a maximum of 0.5 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.Instructions on How to Receive Credit Listen to this podcast in its entirety. Go to gotoper.com/credit and enter code: 8926 Answer the evaluation questions. Request credit using the drop-down menu. You may immediately download your certificate.

When treating hormone-sensitive prostate cancer (mHSPC), one question can be, when is the right time to optimize or intensify therapy? In the latest Oncology Decoded podcast, genitourinary oncologists discuss the use of radiotherapy and define oligometastatic disease including preferred treatment options. The discussion took place during the 2025 ASCO Genitourinary Cancers Symposium. The expert panel consisted of:    Manojkumar Bupathi, MD, MS, executive co-chair of Genitourinary Cancer Research Executive Committee at Sarah Cannon Research Institute; medical oncologist with Rocky Mountain Cancer Centers specializing in solid tumors and genitourinary cancers; Benjamin Garmezy, MD, associate director of Genitourinary Research and executive co-chair of Genitourinary Cancer Research Executive Committee at Sarah Cannon Research Institute (SCRI); medical oncologist at SCRI Oncology Partners specializing in genitourinary cancers; David Morris, MD, MS, president of Urology Associated, PC; Tanya Dorff, MD, professor in the Department of Medical Oncology & Therapeutics Research and section chief of the Genitourinary Disease Program at City of Hope; Mark T. Fleming, MD, medical oncologist at Virginia Oncology Associates; disease chair of the Genitourinary Cancer Research Executive Committee for SCRI at Virginia Oncology Associates. The discussion centered around a challenging case of a 50-year-old male who had hematuria, penile pain, and a high prostate-specific antigen, with imaging revealing a Gleason 4+5 adenocarcinoma and metastatic lymph node involvement.The panel agreed that androgen deprivation monotherapy was insufficient for this patient. The conversation quickly shifted to the optimal intensification strategy, with a focus on balancing efficacy and toxicity. Morris advocated for a combination of radiotherapy and androgen deprivation therapy (ADT) plus an androgen receptor signaling inhibitor, while acknowledging the patient didn’t strictly meet criteria for triplet therapy with chemotherapy. Dorf and Fleming favored doublet therapy with an androgen receptor pathway inhibitor and radiation, but also highlighted the importance of discussing chemotherapy, particularly given the patient’s young age and aggressive disease characteristics.A key point of contention was the role of docetaxel. While some panelists acknowledged its potential benefit, concerns about toxicity and the lack of clear high-burden disease criteria in this case led to a general preference for radiation therapy for local debulking.The discussion also explored the concept of oligometastatic disease, with the panel generally agreeing on a threshold of less than 5 metastatic sites. However, the location of these sites was deemed crucial, with lymph node and bone metastases considered more amenable to radiation therapy than visceral involvement. The importance of multidisciplinary input, including radiation oncology, was emphasized in determining the optimal treatment approach.The use of imaging for surveillance was another key topic. While PSMA PET imaging was considered the gold standard for sensitivity and specificity, challenges with insurance coverage and the need for consistent imaging modalities were acknowledged. The panelists also highlighted the importance of considering de-differentiation and the potential for false positives with PSMA PET scans.Ultimately, the discussion underscored the importance of individualized treatment decisions in mHSPC, considering patient age, disease burden, risk factors, and preferences. The panel emphasized the need for ongoing research to refine treatment strategies and improve outcomes for patients with this complex disease.Physicians’ Education Resource®, LLC, is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for physicians.Physicians’ Education Resource®, LLC, designates this enduring material for a maximum of 0.5 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.Instructions on How to Receive Credit Listen to this podcast in its entirety. Go to gotoper.com/credit and enter code: 3541 Answer the evaluation questions. Request credit using the drop-down menu. You may immediately download your certificate.

During the 2025 ASCO Genitourinary Cancers Symposium, Oncology Decoded held their inaugural podcast with a live filming taking place at the conference. The first episode focused on bladder cancer specifically, neoadjuvant vs adjuvant therapy options and the use of cisplatin vs carboplatin. Meet the expert panel involved in the discussion:    Manojkumar Bupathi, MD, MS, executive co-chair of Genitourinary Cancer Research Executive Committee at Sarah Cannon Research Institute; medical oncologist with Rocky Mountain Cancer Centers specializing in solid tumors and genitourinary cancers; Benjamin Garmezy, MD, associate director of Genitourinary Research and executive co-chair of Genitourinary Cancer Research Executive Committee at Sarah Cannon Research Institute (SCRI); medical oncologist at SCRI Oncology Partners specializing in genitourinary cancers' Petros Grivas, MD, PhD, professor in the Clinical Research Division and clinical director of Genitourinary Cancers Program at Fred Hutch Cancer Center; David Morris, MD, MS, president of Urology Associated, PC. During the discussion on neoadjuvant therapy, the panelist brought up results from the phase 3 NIAGARA trial (NCT03732677) which assessed durvalumab (Imfinzi) along with radical cystectomy and adjuvant chemotherapy followed by radical cystectomy. For those who achieved a pathological complete response (pCR), the median overall survival (OS) was not reached (NR) in the durvalumab arm or the comparator arm (HR, 0.72; 95% CI, 0.387-1.426). For those who did not have a pCR, the median OS was NR in both arms as well (HR, 0.84; 95% CI, 0.660-1.068). The intent-to-treat (ITT) population OS HR was 0.75 (95% CI, 0.59-0.93). In the ITT population, the pCR was 37.3% (95% CI, 33.2%-41.6%) in the durvalumab arm and 27.5% (95% CI, 23.8%-31.6%) in the comparator arm (OR, 1.60-1.23-2.08). Results from this trial then led into the use of cisplatin vs carboplatin. From a urologist perspective, Morris notes that all patients should be afforded the opportunity for neoadjuvant therapy vs being thrown right into surgery. He also mentions this scenario can occur because of the criteria for administering cisplatin. “If I had one message today for our friends and colleagues in practice, do not use carboplatin in the neoadjuvant setting. If you can give cisplatin, we can talk about who can be cisplatin-eligible. If you cannot give cisplatin safely, the options could be radical cystectomy upfront with liminal dissection or clinical trial, if available and eligible, and bladder preservation can be another strategy in these patients,” Grivas said. Grivas backed up his reasoning here because of clinical trials that have been conducted regarding pCR rates. These rates appeared to be lower in those given carboplatin vs those given cisplatin. Because of this, he will not use carboplatin as a neoadjuvant or adjuvant approach for muscle-invasive bladder cancer. Moving forward, they hope to focus on capturing additional data from real-world studies as well as more trials to provide evidence-based research for the treatment of bladder cancer. ReferenceGalsky M, Van Der Heijden M, Catto J, et al. Additional efficacy and safety outcomes and an exploratory analysis of the impact of pathological complete response (pCR) on long-term outcomes from NIAGARA. J Clin Oncol 43, 2025 (suppl 5; abstr 659).Physicians’ Education Resource®, LLC, is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for physicians.Physicians’ Education Resource®, LLC, designates this enduring material for a maximum of 0.5 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.Instructions on How to Receive Credit Listen to this podcast in its entirety. Go to gotoper.com/credit and enter code: 4376 Answer the evaluation questions. Request credit using the drop-down menu. You may immediately download your certificate.