Impact of BCG failure patterns on efficacy of intravesical gemcitabine/docetaxel in high-risk non-muscle-invasive bladder cancer.

OBJECTIVE

To examine the impact of specific Bacillus Calmette-Guérin (BCG) failure phenotypes on treatment outcomes with intravesical gemcitabine/docetaxel in high-risk non-muscle-invasive bladder cancer (HR-NMIBC).

PATIENTS AND

METHODS

A BCG failure was classified according to the United States Food and Drug Administration (FDA)/International Bladder Cancer Group (IBCG) definitions and analysed as early refractory BCG failure, early non-refractory BCG failure, or late BCG relapse. Kaplan-Meier methods were used to estimate recurrence-free survival (RFS), high-grade RFS (HG-RFS), and progression-free survival (PFS). Multivariable Cox proportional hazards models, adjusted for histology, multifocality, and tumour size, were used to assess the association between BCG failure patterns and oncological outcomes.

RESULTS

Among the 143 patients included, 72 had early non-refractory BCG failure, 36 had early refractory BCG failure, and 35 experienced late BCG relapse. The median follow-up was 12 months. At 12 months, the RFS was 67% (95% confidence interval [CI] 55-82%) in early non-refractory BCG failure, 54% (95% CI 36-82%) in early refractory BCG failure, and 84% (95% CI 70-100%) in late BCG relapse (P < 0.05). Corresponding HG-RFS rates were 75% (95% CI 64-88%), 58% (95% CI 39-87%), and 87% (95% CI 75-100%), respectively (P < 0.05). The PFS remained >90% across all groups at 12 months. On multivariable analysis, both early non-refractory BCG failure (adjusted hazard ratio [aHR] 3.20, 95% CI 1.31-7.82; P = 0.011) and early refractory BCG failure (aHR 3.59, 95% CI 1.28-10.1; P = 0.015) were associated with a significantly higher risk of recurrence compared with late BCG relapse, with consistent findings for HG recurrence.

CONCLUSIONS

Gemcitabine/docetaxel demonstrated meaningful activity across all BCG failure types, with late BCG relapsing patients achieving the most favourable outcomes and refractory disease showing the poorest control. These findings underscore the clinical relevance of distinguishing BCG failure subtypes when selecting candidates for post-BCG intravesical gemcitabine/docetaxel and designing future prospective trials.