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.

The 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cisplatin/gemcitabine with nivolumab (Opdivo), is also mentioned as a prior standard of care, though generally superseded by enfortumab vedotin/pembrolizumab.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.

For 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.

References

1.        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.4571

2.        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.4500

3.        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.

Reference

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/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.

1. 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.LBA5006

2. 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.4503

3. 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: 

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.

Several 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.

The 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. 

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.   

References

1.        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/NEJMoa2312695

2.         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: 

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.4562

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.

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:

   

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.

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:

   

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. 

Reference

Galsky 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.