How to cite: Petrylak DP. “Session 1: BCG-Unresponsive NMIBC.” Grand Rounds in Urology. August 2026. Accessed Oct 2026. https://grandroundsinurology.com/bcg-unresponsive-nmibc/
Summary
In this presentation from the UroCancer Interdisciplinary Forum 2026, Daniel P. Petrylak, MD, Professor of Medicine, Smilow Cancer Center, Yale University, New Haven, Connecticut, reviews the current treatment landscape for Bacillus Calmette-Guérin (BCG)-unresponsive non-muscle-invasive bladder cancer, focusing on the balance between bladder preservation strategies and timely radical cystectomy. He notes that recurrence remains common after BCG therapy and that maintenance treatment compliance rates remain relatively low, creating an ongoing need for more effective therapies.
Dr. Petrylak examines clinical trials evaluating immune checkpoint inhibitors combined with BCG, including CREST and POTOMAC. Although these studies demonstrate modest improvements in event-free or disease-free survival, he notes that the absolute clinical benefit is relatively small while systemic toxicity and treatment costs increase. He raises concerns about exposing patients with localized disease to systemic immunotherapy and questions whether earlier use of checkpoint inhibitors may influence future treatment options if metastatic disease develops.
Dr. Petrylak reinforces that radical cystectomy remains the established standard of care for appropriate patients. He summarizes evidence demonstrating improved progression-free outcomes with early cystectomy compared with delayed surgery and stresses that prolonged bladder-preserving treatment may allow disease progression in selected patients.
Dr. Petrylak then discusses currently available bladder-preserving therapies, including gemcitabine plus docetaxel, pembrolizumab, nadofaragene firadenovec, N-803 plus BCG, and TAR-200. He reviews emerging data on intravesical drug delivery systems and novel biologic therapies, emphasizing that most available evidence comes from single-arm Phase II studies with varying patient populations and study designs.
Dr. Petrylak argues that patient selection remains the most important factor in treatment planning. While new therapies continue to expand bladder preservation options, clinicians must carefully balance efficacy, toxicity, cost, and the potential consequences of delaying radical cystectomy in patients at risk for progression.
ABOUT THE AUTHOR
Daniel P. Petrylak, MD, is a Professor of Medicine, specializing in Medical Oncology and Urology, and Chief of Genitourinary Oncology at Yale University Cancer Center in New Haven, Connecticut. Dr. Petrylak is an internationally renowned medical oncologist and is considered a pioneer in the research and development of new drugs and treatments to fight cancers of the prostate, bladder, and kidney.
