High-Risk NMIBC: Is BCG Still the Best Option?

How to cite: Shore ND. High-Risk NMIBC: Is BCG Still the Best Option? Grand Rounds in Urology. December 2025. Accessed Apr 2026. https://grandroundsinurology.com/high-risk-nmibc-is-bcg-still-the-best-option/

Summary

Neal Shore, MD, FACS, Medical Director, Carolina Urologic Research Center, Myrtle Beach, South Carolina, reviews whether Bacillus Calmette-Guérin (BCG) remains the optimal standard of care for patients with BCG-naïve high-risk non–muscle invasive bladder cancer (NMIBC) in light of recent phase 3 data combining BCG with immune checkpoint inhibitors. He focuses on the biological rationale, trial design, efficacy outcomes, and safety considerations of adding immunotherapy to traditional intravesical treatment.

Dr. Shore begins with a review of persistent unmet needs in high-risk NMIBC, including high rates of recurrence, progression, and residual disease following transurethral resection of bladder tumor (TURBT). He emphasizes that TURBT quality remains a critical determinant of outcomes and that incomplete resection and underdetection of carcinoma in situ (CIS) continue to contribute to treatment failure and progression to muscle-invasive disease.

The presentation then shifts to the rationale for combining BCG with immune checkpoint inhibition. Dr. Shore explains how BCG alters the tumor microenvironment, enhances antigen presentation, and activates CD8-positive T cells, creating a biologic foundation along with PD-1 or PD-L1 inhibition.

Key data from the phase 3 POTOMAC and CREST trials are reviewed in detail. In POTOMAC, the addition of durvalumab to BCG induction and maintenance resulted in a statistically significant and clinically meaningful improvement in disease-free survival compared with BCG alone, with early and sustained separation of survival curves and no detriment in overall survival at extended follow-up. CREST demonstrated similar benefits with sasanlimab plus BCG, including improved event-free survival and durable complete responses in patients with CIS.

Safety data from both trials are discussed, highlighting manageable immune-related adverse events, no treatment-related deaths, and toxicity profiles consistent with prior checkpoint inhibitor experience. Dr. Shore concludes that while BCG remains a foundational therapy, combination strategies may represent the next evolution of care for selected patients with high-risk NMIBC, pending regulatory review and shared decision-making.