[Immune checkpoint inhibition plus Bacillus Calmette-Guerin (BCG) therapy in BCG-naive high-risk non-muscle-invasive bladder cancer: a critical review in the context of current evidence].

Abstract

Background: Intravesical Bacillus Calmette-Guerin (BCG) therapy following transurethral resection (TURBT) remains an important standard treatment for high-risk non-muscle-invasive bladder cancer (NMIBC). Recent phase III trials have evaluated the addition of immune checkpoint inhibitors (IO) to further reduce recurrence rates.

Methods: This review synthesizes data from the CREST (sasanlimab), POTOMAC (durvalumab), and ALBAN (atezolizumab) trials, focusing on surgical quality, BCG maintenance duration, and primary endpoint definitions.

Results: CREST and POTOMAC demonstrated significant improvements in event-free or disease-free survival (both hazard ratio [HR] 0.68) when a 2-year BCG maintenance schedule was followed. In contrast, the ALBAN trial (HR 0.98) failed its primary endpoint. Key reasons for this discrepancy include the shortened BCG maintenance (1 year) and the inclusion of low-grade recurrences in the primary endpoint, which by international consensus do not constitute BCG failure. Data also show that IO cannot compensate for the omission of BCG maintenance. Severe systemic toxicity (grade 3-5) increased substantially with the combination therapy (up to 29%).

Conclusion: Combination therapy strictly necessitates the full BCG maintenance schedule. Given the significant systemic toxicity and the current lack of a demonstrated overall survival benefit, careful patient selection is mandatory.