Long-term Oncological Outcomes for Patients with Non-muscle-invasive Bladder Cancer Treated with Bacillus Calmette-Guérin (BCG): A Comparative Analysis of Adequate Versus Inadequate BCG Treatment

Abstract

Background and objective: Intravesical bacillus Calmette-Guérin (BCG) instillation is recommended for intermediate-risk (IR) and high-risk (HiR) non-muscle-invasive bladder cancer (NMIBC). There are limited comparisons of long-term outcomes between adequate and inadequate BCG.

Methods: We analyzed data from a multicenter European database (2010-2024) for 1558 patients diagnosed with IR- or HiR-NMIBC who underwent BCG treatment and received at least five BCG instillations. Adequate BCG was defined as at least five of six induction instillations and two of three maintenance doses, or two of six doses of a reinduction course. A 3-mo landmark analysis was conducted. Recurrence-free survival (RFS), high-grade RFS (HG-RFS), progression-free survival (PFS), and overall survival (OS) were estimated using inverse probability of treatment weighting (IPTW)-adjusted Kaplan-Meier curves and IPTW-adjusted multivariable Cox regression models. Cancer-specific mortality (CSM) was assessed via cumulative incidence curves and Fine-Gray competing-risks regression analysis.

Key findings and limitations: The cohort included 606 IR-NMIBC (39%), 840 HiR-NMIBC (54%), and 112 very HiR (VHR)-NMIBC (7.1%) cases. Adequate BCG was administered to 1226 patients (78%). Among 1239 patients (80%) with documented treatment termination reasons, 503 (41%) completed guideline-recommended treatment and 150 (12%) discontinued because of BCG intolerance. Over median follow-up of 37 mo, adequate BCG was associated with higher IPTW-adjusted 5-yr RFS (72% vs 52%; hazard ratio [HR] 0.40, 95% confidence interval [CI] 0.31-0.85; p < 0.001), HG-RFS (83% vs 68%; HR 0.43, 95% CI 0.32-0.58; p < 0.001), PFS (92% vs 85%; HR 0.47, 95% CI 0.30-0.74; p = 0.001), and OS (88% vs 71%; HR 0.52, 95% CI 0.37-0.74; p = 0.001). CSM rates were comparable between the groups (3% vs 4.9%; p = 0.3).

Conclusions and clinical implications: Adequate BCG, as defined by the International Bladder Cancer Group (IBCG), was associated with significantly better RFS, PFS, and OS. These findings support use of the IBCG definition as a standardized benchmark for BCG exposure. However, further prospective validation to confirm causality is needed.

Keywords: Adequate intravesical treatment; Bacillus Calmette-Guérin; Non–muscle-invasive bladder cancer; Oncological outcomes; Survival.