Timing of FDA-Defined Adequate BCG Therapy and Oncologic Outcomes in High-Risk Non-Muscle-Invasive Bladder Cancer

INTRODUCTION: Adequate bacillus Calmette-Guérin (BCG) therapy, as defined by the U.S. Food and Drug Administration (FDA), is widely used in clinical trial eligibility criteria and regulatory frameworks, yet its prognostic relevance in real-world practice remains incompletely understood. We evaluated the association between time-dependent completion of adequate BCG therapy and oncologic outcomes in patients with high-risk non-muscle-invasive bladder cancer (HR NMIBC). METHODS: This retrospective cohort study included 188 patients with treatment-naïve HR NMIBC treated with BCG. Adequate BCG therapy was defined according to FDA criteria, and patients were categorized according to the timing of achieving adequate BCG therapy. In a landmark analysis, Cox regression models were used to evaluate the effect of clinicopathologic characteristics and timing of adequate BCG therapy completion on conditional high-grade recurrence-free survival (HG-RFS). RESULTS: The proportion of patients completing adequate BCG therapy increased over time, reaching 61.7% by 6 months from induction initiation. Among patients included in the landmark analysis (n = 140), completion of adequate BCG therapy between 4 and 5 months after initiation of induction BCG was associated with significantly improved HG-RFS compared with completion by 4 months (hazard ratio 0.31, 95% confidence interval 0.12-0.79). CONCLUSIONS: Among patients who met FDA-defined adequate BCG criteria, completion of therapy between 4 and 5 months was associated with the most favorable oncologic outcomes observed in this cohort. These findings provide real-world context for current definitions of adequate BCG exposure and suggest that the temporal pattern of treatment delivery may be an important consideration when evaluating BCG-related outcomes.