Bladder, Kidney, and Prostate Cancer Highlights From ASCO GU 2026
Key Points
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The CREST and POTOMAC trials showed the addition of immunotherapy to standard Bacillus Calmette-Guérin (BCG) treatment improved survival end points in patients with non–muscle-invasive bladder cancer (NMIBC).
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In the KEYNOTE-B15/EV-304 trial, perioperative enfortumab vedotin (EV) plus pembrolizumab was superior to standard neoadjuvant chemotherapy in cisplatin–eligible patients with muscle-invasive bladder cancer (MIBC).
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LITESPARK-011/LITESPARK-022: belzutifan combinations in different lines of therapy for renal cell carcinoma (RCC).
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CAPITello-281: capivasertib plus abiraterone tolerability in PTEN-deficient metastatic prostate cancer.
Key ASCO GU 2026 Trials in Bladder, Kidney, and Prostate Cancers
On the Oncology Brothers podcast, Rahul Gosain, MD, MBA, of Wilmot Cancer Institute, and Rohit Gosain, MD, of Roswell Park Comprehensive Cancer Center, were joined by Petros Grivas, MD, PhD, of Fred Hutchinson Cancer Center, to discuss key trials in bladder, kidney, and prostate cancers, including those presented at the 2026 American Society of Clinical Oncology Genitourinary Cancers Symposium (ASCO GU 2026). The doctors discussed data from the CREST, POTOMAC, KEYNOTE-B15/EV-304, LITESPARK-011, LITESPARK-022, and CAPItello-281 trials.
CREST and POTOMAC: Adding Immunotherapy to BCG in NMIBC
The CREST and POTOMAC studies added sasanlimab and durvalumab, respectively, to standard BCG therapy in BCG–naïve patients with high-risk NMIBC. Sasanlimab was administered subcutaneously for 2 years, while durvalumab was administered intravenously for 1 year. Both studies showed that the addition of immunotherapy improved survival endpoints, with a hazard ratio (HR) of 0.68 each for disease-free survival (DFS) in POTOMAC and event-free survival (EFS) in CREST.
It’s unclear as of now if these studies will update the BCG standard of care in NMIBC. Both agents are pending regulatory approval; however, the European Union filing for sasanlimab was withdrawn by the manufacturer, and durvalumab is still being evaluated in the United States in the PATAPSCO trial. In addition, POTOMAC was not powered to evaluate the effect of durvalumab on other end points, such as progression to cystectomy, said Dr. Grivas. If either agent is approved for this indication, medical oncologists may need to become more involved in the management of patients with NMIBC to administer the drugs and manage immune-related side effects.
Expanding EV Plus Pembrolizumab in MIBC Based on KEYNOTE-B15/EV-304
One of the most-discussed presentations at ASCO GU 2026 was the positive data for perioperative EV plus pembrolizumab in MIBC from the KEYNOTE-B15/EV-304 trial. Previously, EV plus pembrolizumab was the standard treatment for cisplatin–ineligible patients with MIBC based on the KEYNOTE-905/EV-303 trial. The KEYNOTE-B15/EV-304 built upon these data and showed that perioperative EV plus pembrolizumab improved EFS (HR, 0.53; 95% CI, 0.41-0.70; P < .0001) and overall survival (OS; HR, 0.65; 95% CI, 0.48-0.89; P = .0029) versus neoadjuvant gemcitabine and cisplatin in cisplatin–eligible patients.
While antibody-drug conjugates like EV require management of potential toxicities like rash, neuropathy, and hyperglycemia, the data from both KEYNOTE-905/EV-303 and KEYNOTE-B15/EV-304 showed that EV plus pembrolizumab did not compromise the ability of patients to progress to curative radical cystectomy. Overall, the data for EV plus pembrolizumab are really remarkable and this regimen is immediately ready to be implemented in clinical practice, said Dr. Grivas.
Belzutifan for RCC in LITESPARK-022 and LITESPARK-011
During the discussion, Drs. Rahul and Rohit Gosain briefly highlighted data for belzutifan combinations in kidney cancer. In RCC, the adjuvant standard of care has been 1 year of pembrolizumab based on KEYNOTE-564. The LITESPARK-022 trial sought to build on this standard by combining pembrolizumab with belzutifan. In the trial, belzutifan plus pembrolizumab improved DFS compared with pembrolizumab alone (HR, 0.72; 95% CI, 0.59-0.87; P = .0003).
Separately, in the LITESPARK-011 trial, belzutifan plus lenvatinib was evaluated against cabozantinib in patients with unresectable, locally advanced, or metastatic clear cell RCC who progressed after first-line or second-line anti–PD-(L)1 therapy. In this trial, the addition of belzutifan improved progression-free survival (PFS; HR, 0.70; 95% CI, 0.59-0.84; P = .0007) and OS (HR, 0.85; 95% CI, 0.68-1.05; P = .061).
Both trials support the value of hypoxia-inducible factor-2α inhibition in the treatment of patients with RCC, although belzutifan use requires careful management of anemia and potential hypoxia-related side effects, said Dr. Rahul Gosain.
CAPItello-281: Capivasertib Plus Abiraterone in mHSPC
The phase 3 CAPItello-281 trial evaluated capivasertib plus abiraterone versus placebo plus abiraterone in patients with PTEN–deficient metastatic hormone–sensitive prostate cancer (mHSPC). The median radiographic PFS was 33.2 months (95% CI, 28.5-44.2) in the capivasertib arm compared with 25.7 months (95% CI, 22.0-29.9) in the control arm (HR, 0.81; 95% CI, 0.66-0.98; P = .034). Capivasertib was associated with more symptomatic adverse events and a decline in self-reported physical wellbeing, but not a decline in work, sleep, or overall health-related quality of life metrics, according to a patient-reported outcome analysis presented at ASCO GU 2026.
While follow-up in CAPItello-281 is still ongoing, it’s under debate whether the radiographic PFS benefit alone with capivasertib is enough to offset the increased risk of side effects including diarrhea, rash, pruritus, hyperglycemia, and fatigue. Use of this regimen should be an individualized discussion between patients and providers that includes education of potential toxicities and related management strategies, said Dr. Grivas.