Prognostic impact of Bacillus Calmette-Guérin interruption at the time of induction and consolidation

CONTEXT: Intravesical Bacillus Calmette-Guérin (BCG) is a cause of bladder and systemic toxicity that is difficult to prevent and is responsible for treatment drop out in bladder cancer patients. More recently, BCG shortage has become the main cause of incomplete treatment. AIMS: The aim of this study was to examine the impact on long-term prognosis of bladder cancer patients following discontinuation of BCG instillations. SETTINGS AND DESIGN: In this retrospective study, data were examined from 333 consecutive nonmuscle invasive bladder cancer patients treated from 2005 to 2015 by transurethral resection (TUR) and had undergone adjuvant BCG therapy after TUR. SUBJECTS AND METHODS: Rate of complete cure, the reason for the interruption, toxicity, and the associations between discontinuance of BCG therapy, tumor characteristics, association with carcinoma in situ and tumor recurrence or progression were analyzed. STATISTICAL ANALYSIS USED: Recurrence and progression-free survival rate curves were estimated using the Kaplan-Meier method and were compared using the log-rank test. Univariate and multivariate analyses were performed using the Cox proportional hazards model. Differences among groups were considered as statistically significant when P < 0.05. RESULTS: Overall, 303 patients were eligible for analysis. Median follow up was 36 (confidence interval: 7–120) months. A total of 55 (18.1%) had <6 installations (Group I); 87 (28.7%) completed induction and 1-year maintenance (Group III); and 161 (53.1%) completed the induction course, but not the 1-year maintenance (Group II). Grade III–IV toxicity rates were significantly higher in Group I than Group II and III. Interruption for BCG shortage was the main cause of interrupting BCG in Group II. Multivariate analysis showed that discontinuation of BCG induction therapy was an independent predictor for tumor recurrence (P < 0.001) and 1-year BCG maintenance therapy for tumor progression (P = 0.005). CONCLUSIONS: Discontinuation of BCG therapy has a significantly deleterious effect on tumor recurrence and progression rates. Although BCG toxicity is a major cause of drop out, BCG shortage became a major cause of discontinuation. All effort must be done today to restore normal production of BCG worldwide.