ASCO GU 2026: Key Updates in Bladder, Prostate, and Kidney Cancer

Charbel Matar, MD The George Washington University Hospital

Key Points

• Enfortumab vedotin plus pembrolizumab is emerging as a potential perioperative standard for muscle-invasive bladder cancer (MIBC), demonstrating markedly higher pathologic complete response (pCR) rates compared with historical chemotherapy approaches.

• Treatment intensification in metastatic prostate cancer continues to evolve, with increasing use of prostate-specific membrane antigen (PSMA) PET, growing emphasis on molecular testing and imaging, and ongoing debate around doublet versus triplet systemic therapy.

• Adjuvant pembrolizumab remains the standard for high-risk renal cell carcinoma (RCC), although emerging combinations such as belzutifan plus pembrolizumab may further reshape the adjuvant landscape.

The 2026 American Society of Clinical Oncology Genitourinary Cancers Symposium (ASCO GU 2026) showcased significant progress across bladder, prostate, and kidney cancers. With the rapid expansion of therapeutic options, clinicians increasingly face the challenge of translating emerging data into practical treatment strategies. The following overview summarizes key findings most relevant to community oncologists.

Immunotherapy Combinations in Non–Muscle Invasive Bladder Cancer

Bacillus Calmette-Guérin (BCG) remains the standard treatment for high-risk non–muscle-invasive bladder cancer (NMIBC). At ASCO GU 2026, investigators reviewed trials combining BCG with immune checkpoint inhibitors, including the CREST and POTOMAC studies.

Both trials demonstrated improved event-free survival with the addition of immunotherapy. However, the clinical benefit appears modest and must be balanced against toxicity. Ashish Kamat, MD, MBBS, FACS, of MD Anderson Cancer Center, said that the absolute improvement was relatively small and accompanied by increased immune-related adverse effects.

Experts emphasized that these regimens may be best suited for selected high-risk patients pursuing bladder preservation, rather than replacing BCG broadly.

EV-Pembrolizumab in MIBC

One of the most practice-relevant updates involved enfortumab vedotin plus pembrolizumab (EV-pembro) in MIBC, building on its established role in metastatic disease.

Historically, neoadjuvant cisplatin-based chemotherapy, such as gemcitabine and cisplatin, has been the standard. Data discussed at ASCO GU 2026 demonstrated significantly higher pCR rates with EV-pembro—approximately 55% versus 30% with chemotherapy.

Based on these findings, Andrea Apolo, MD, of National Cancer Institute, said that the regimen could become a new standard of care for eligible patients.

As EV-based therapy moves earlier in treatment, clinicians must monitor toxicities such as neuropathy, rash, and hyperglycemia associated with EV. Furthermore,  earlier use of EV-pembro raises questions about treatment sequencing for patients who relapse. Potential options include platinum chemotherapy or biomarker-directed therapies such as FGFR inhibitors or HER2-targeted agents. Prospective data are still needed to guide optimal sequencing strategies.

Prostate Cancer: PSMA PET is Reshaping Staging

PSMA PET imaging continues to redefine prostate cancer staging by detecting metastatic disease earlier than conventional imaging. However, its high sensitivity also introduces challenges, including false-positive findings.

Experts highlighted that isolated lesions—particularly solitary rib lesions—may frequently be benign. Clinicians should therefore interpret PSMA PET results cautiously and avoid prematurely abandoning potentially curative treatment strategies.

Salvage Radiation in Biochemical Recurrence

For patients with biochemical recurrence after prostatectomy, early salvage radiation therapy remains a key intervention.

Data from the POSEIDON meta-analysis presented at ASCO GU 2026 suggest that radiation alone is sufficient for most patients, with androgen deprivation therapy (ADT) reserved for those with higher prostate-specific antigen levels.

This approach may reduce overtreatment and limit exposure to hormonal therapy.

Treatment Intensification Debate

In metastatic castration-sensitive prostate cancer, treatment intensification remains an active area of investigation. Current strategies include ADT plus an androgen receptor pathway inhibitor (ARPI) or triplet therapy that adds docetaxel chemotherapy.

Triplet therapy appears most beneficial in patients with high-volume or visceral metastatic disease, although ongoing trials aim to clarify the incremental benefit of chemotherapy in the modern ARPI era.

Standard of Care: Adjuvant Pembrolizumab in RCC

For patients with high-risk localized renal RCC, adjuvant pembrolizumab remains the standard following nephrectomy.

Eligible patients include those with T2 grade 4 tumors, T3 or higher disease, or patients undergoing metastasectomy within one year of diagnosis. In this population, pembrolizumab has demonstrated both disease-free and overall survival benefits.

Emerging HIF-2α–Targeted Combinations

The LITESPARK-022 trial evaluating belzutifan plus pembrolizumab in the adjuvant setting was another key focus of discussion. Belzutifan targets the hypoxia-inducible factor-2α pathway, a central driver of clear-cell RCC biology.

Although final results were pending at the time of discussion, investigators expressed optimism that the combination may improve outcomes beyond pembrolizumab alone. Belzutifan is associated with anemia and hypoxia, which require careful monitoring.

Cytoreductive Nephrectomy Reconsidered

With increasingly effective systemic therapies available, the role of cytoreductive nephrectomy in metastatic RCC has diminished. Current practice often prioritizes systemic therapy first, reserving surgery for selected cases such as symptomatic primary tumors or discordant disease responses.

Future Implications

ASCO GU 2026 highlighted the continued shift toward earlier use of highly active systemic therapies across genitourinary cancers. From antibody-drug conjugates in bladder cancer to biomarker-guided strategies in prostate cancer and HIF-targeted therapies in RCC, treatment paradigms are rapidly evolving.

For community oncologists, integrating these advances into clinical practice while balancing efficacy, toxicity, and patient preferences will be critical as new data continue to reshape the field.