GU Experts Weigh In on Trials That Could Redefine Bladder, Kidney, and Prostate Cancer Care

During an Advancements in Oncology event held in conjunction with the 2026 American Society of Clinical Oncology (ASCO) Annual Meeting, the Oncology Brothers Rahul Gosain, MD, MBA, of Wilmot Cancer Institute, and Rohit Gosain, MD, of Roswell Park Comprehensive Cancer Center, led an expert genitourinary (GU) cancer panel that reviewed recent advances in bladder, kidney, and prostate cancers. Panelists included Andrea Apolo, MD, of the National Cancer Institute/NIH; Tian Zhang, MD, of UT Southwestern Medical Center; and Sumanta K. Pal, MD, of City of Hope Comprehensive Cancer Center.

Their discussion focused on several key clinical trials that may prove to be practice-changing within the GU cancer space.

Bladder Cancer: POTOMAC, EV-302, and Evolving Treatment Sequencing 

In bladder cancer, durvalumab plus BCG for high-risk non–muscle-invasive bladder cancer (NMIBC), as evaluated in the phase 3 POTOMAC trial (NCT03528694), demonstrated improved disease-free survival (DFS) with durvalumab plus BCG induction and maintenance versus BCG alone (hazard ratio [HR], 0.68) without an overall survival (OS) benefit. Dr. Apolo expressed hesitance about finding the ideal patient for this combination, given immunotherapy risks and relatively favorable outcomes in this population. Furthermore, management would now require the involvement of medical oncologists for the large NMIBC patient population, which may be logistically challenging.

In muscle-invasive and metastatic urothelial carcinoma, perioperative and frontline enfortumab vedotin plus pembrolizumab (EV/pembrolizumab), supported by EV-303/EV-304 and extended follow-up from EV-302, continues to show durable OS benefit compared with platinum-based chemotherapy, with a notable proportion of patients converting from partial to complete responses (CRs) and 83.6% of patients achieving CR alive at 3.5 years.

Post-EV/pembrolizumab, Dr. Apolo said that platinum-based chemotherapy is a common second-line option. Post EV/platinum, patients with pathogenic FGFR3 mutations can receive erdafitinib, while the National Comprehensive Cancer Network Bladder Cancer guidelines now allow trastuzumab deruxtecan for patients with either HER2 IHC 2+ or 3+ status (FDA approval remains for IHC 3+ only). Taxane monotherapy remains available, but peripheral neuropathy post EV and/or platinum may limit use, and sacituzumab govitecan remains available off-label with granulocyte-colony stimulating factor support.

Reassessing Adjuvant Therapy and Optimizing Frontline Selection in RCC

In renal cell carcinoma, the phase 3 RAMPART trial showed improved DFS with adjuvant durvalumab plus tremelimumab versus active monitoring (HR, 0.65) but no OS benefit, and no DFS benefit with durvalumab monotherapy. With these results, Dr. Pal said that adjuvant pembrolizumab remains the standard of care. Emerging data from LITESPARK-022 suggest improved DFS with pembrolizumab plus belzutifan versus pembrolizumab alone (HR, 0.72), with hypoxia and anemia as key adverse events requiring monitoring and supportive management. The combination may be best reserved for patients at highest risk of relapse, according to Dr. Pal.

In the metastatic setting, treatment selection balances durability versus rapid disease control, with dual immune checkpoint blockade favored for asymptomatic patients seeking durable responses and VEGF-tyrosine kinase inhibitor (TKI)–based combinations preferred for symptomatic disease. Results from LITESPARK-011 demonstrating superior efficacy of lenvatinib plus belzutifan versus cabozantinib in the second line may influence earlier-line TKI selection. Dr. Zhang said that later-line options typically include belzutifan (if not previously used), tivozanib, pazopanib, or everolimus.

PROTEUS and TALAPRO-3 Drive New Approaches in Prostate Cancer

The phase 3 PROTEUS trial (NCT03767244), which was featured at ASCO’s plenary session, demonstrated benefit with perioperative androgen deprivation therapy (ADT) plus apalutamide administered before and after prostatectomy in high-risk prostate cancer, although the role of surgery compared with radiation-based approaches remains individualized, particularly in very high-risk populations, Dr. Zhang said. However, young patients may do well with surgery and want to avoid radiation toxicity, according to the panelists.

Dr. Zhang also noted the role of PSMA PET imaging, which can help to identify disease sites (especially regarding identifying sites of metastatic disease) and as criterion for use of Pluvicto therapy. PSMA PET avidity (e.g. standardized uptake value above 10) represents a potential marker of activity to help identify patients in which alternative treatment options should be used before Pluvicto.

In homologous recombination repair–mutated metastatic castration-sensitive prostate cancer, TALAPRO-3 showed improved radiographic progression-free survival with talazoparib plus enzalutamide and ADT versus enzalutamide and ADT alone (HR, 0.48), with benefit observed across BRCA and non-BRCA subgroups.

For PTEN-mutated prostate cancer, capivasertib plus abiraterone demonstrated clinical activity in the phase 3 CAPItello-281 trial and is under regulatory review. Ongoing development of bispecific T-cell engagers and androgen receptor degraders may further expand therapeutic options.

References

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