ASCO GU 2026: Novel Therapies Transform Genitourinary Oncology
March 13, 2026
Key Points
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Bladder Cancer: Perioperative enfortumab vedotin (EV) plus pembrolizumab is a potential new standard of care for muscle-invasive disease. Bacillus Calmette-Guérin (BCG) combined with immunotherapy offers modest benefits with added toxicity, reserving it for select high-risk non-muscle invasive cases.
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Prostate Cancer: Treatment intensification (e.g., triplet therapy in metastatic castration-sensitive disease) and careful androgen receptor pathway inhibitor (ARPI) selection based on toxicity profiles are critical.
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Renal Cell Carcinoma: Frontline management relies heavily on immunotherapy (IO) plus tyrosine kinase inhibitor (TKI) regimens. Emerging HIF2 inhibitor combinations are expanding systemic therapy options.
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Biomarkers: Molecular profiling, germline testing, and circulating tumor DNA (ctDNA) increasingly inform decisions but largely remain investigational.
The 2026 ASCO Genitourinary Cancers Symposium (ASCO GU 2026) unveiled promising data highlighting the rise of antibody-drug conjugates (ADCs), novel immunotherapy combinations, and targeted therapies.
During the Advancements in Oncology live event, the Oncology Brothers, Rahul Gosain, MD, MBA, of Wilmot Cancer Institute, and Rohit Gosain, MD, of Roswell Park Comprehensive Cancer Center, led a panel discussion translating emerging data into practical applications for community oncology.
Panelists included Andrea Apolo, MD, of National Cancer Institute; Alan Bryce, MD, of City of Hope; Toni Choueiri, MD, Dana-Farber Cancer Institute; Ashish Kamat, MD, of MD Anderson Cancer Center; Sumanta Pal, MD, FASCO, of City of Hope; and Karine Tawagi, MD, of University of Illinois Cancer Center.
IO and ADC Strategies Reshape Bladder Cancer Treatment
In non-muscle invasive disease, the CREST and POTOMAC trials showed improved event-free survival when systemic immunotherapy was added to intravesical BCG. However, Dr. Kamat noted the absolute benefit is modest (5–7%) against a high rate of immune-related toxicities (20–30%). This strategy is best limited to highly selected, very high-risk patients seeking to avoid cystectomy. Dr. Apolo cautioned about the logistical and toxicity burdens introduced for a localized disease.
Perioperative EV plus pembrolizumab produced an approximately55% pathologic complete response rate compared with a historical rate of approximately 30% with cisplatin in muscle-invasive bladder cancer. Dr. Apolo called this regimen potentially practice-changing. However, clinicians must manage ADC-specific toxicities such as neuropathy, dermatologic reactions, and hyperglycemia, she said. Post-relapse sequencing often reverts to platinum-based chemotherapy, with targeted therapies such as erdafitinib or trastuzumab deruxtecan reserved for later lines of treatment.
Advances in Imaging and Systemic Therapy in Prostate Cancer
For staging localized high-risk prostate cancer, prostate-specific membrane antigen (PSMA) PET imaging is highly sensitive but risks false positives in isolated lesions, Dr. Tawagi said. For biochemical recurrence, the POSEIDON meta-analysis confirmed early salvage radiation remains the primary curative intervention. Dr. Bryce added that androgen deprivation therapy (ADT) is often unnecessary when prostate-specific antigen levels are low.
In metastatic castration-sensitive prostate cancer, triplet therapy (ADT plus docetaxel plus ARPI) benefits younger patients with de novo or visceral metastases. Comorbidities dictate ARPI selection: enzalutamide and apalutamide are associated with higher risks of fatigue and falls, while darolutamide has a more favorable neurologic profile, making it a preferred option for some older patients. In other targeted strategies, PARP inhibitors remain restricted to castration-resistant settings, and AKT inhibition (CAPItello trials) improved progression-free survival but lacked overall survival benefits and carries toxicity concerns.
Renal Cell Carcinoma: Treatment Selection and Sequencing
Adjuvant pembrolizumab remains the standard of care following nephrectomy in renal cell carcinoma (RCC) for high-risk patients (T2 grade 4, ≥T3, or post-metastasectomy), according to Dr. Pal. Combination strategies evaluating pembrolizumab with the HIF2 inhibitor belzutifan are currently underway. In metastatic settings, IO plus TKI combinations dominate. Dr. Choueiri explained that dual checkpoint blockade (nivolumab plus ipilimumab) is preferred for sarcomatoid features, while IO plus TKI is favored for rapid tumor control.
Post-progression, patients often transition to targeted therapies like tivozanib, reserving belzutifan for later lines. Managing belzutifan-related toxicities, specifically anemia and hypoxia, with erythropoiesis-stimulating agents allows patients to sustain therapy longer.
Cross-Cutting Themes
Balancing therapeutic efficacy with toxicity and patient burden remains an important consideration as systemic therapies move earlier in the disease course. Panelists highlighted the need to carefully weigh the potential benefits of intensified treatment strategies against the added risks of treatment-related toxicities and the practical implications for patients, including increased monitoring, clinic visits, and management of adverse effects such as immune-related events, neuropathy, metabolic complications, and other therapy-associated toxicities.
In parallel, the role of biomarkers in guiding treatment decisions continues to evolve across genitourinary (GU) oncology. Tools such as ctDNA, molecular profiling, and advanced imaging modalities, including PSMA PET, are increasingly being incorporated into clinical discussions and research. However, the panelists emphasized that many of these approaches remain areas of active investigation, with ongoing uncertainty about how best to use them to guide treatment selection, sequencing, and monitoring in routine clinical practice.
Overall, the panel discussion underscored the rapid pace of change across the GU oncology landscape. Emerging perioperative strategies in bladder cancer, evolving treatment intensification approaches in prostate cancer, and expanding targeted therapy options in RCC are reshaping clinical decision-making. As these advances are integrated into practice, the speakers emphasized the importance of patient selection, multidisciplinary collaboration, and careful clinical judgment when applying new data in real-world settings.