A Systematic Review and Meta-Analysis of the Effectiveness and Safety of Immune Checkpoint Inhibitors in Patients With BCG-Unresponsive Non-Muscle-Invasive Bladder Cancer.

The primary cancer of the urinary system is bladder cancer, which includes 2 subtypes: muscle-invasive bladder cancer (MIBC) and non-muscle-invasive bladder cancer (NMIBC). Intravesical Bacillus Calmette-Guérin (BCG) therapy remains the gold standard for treating individuals with high-risk NMIBC. However, disease development and recurrence pose serious clinical problems. This study aims to evaluate the safety and efficacy of immune checkpoint inhibitors (ICIs) as innovative therapeutic approaches for patients with BCG-unresponsive NMIBC. We conducted this study according to the PRISMA guidelines. We systematically reviewed clinical trials that evaluated ICIs as a treatment for BCG-unresponsive NMIBC and reported predefined efficacy and safety outcomes. We synthesized data using R software and evaluated the risk of bias using the ROBINS-I tool. Nine studies (488 patients) were included in the review, of which 6 were pooled in the meta-analysis. Following ICI therapy, the complete response (CR) rates were 36% at 3 months, 25% at 6 months, and 18% at twelve months. Across all studies, 14% of patients had a radical cystectomy (RC), with the lowest rates occurring in patients receiving atezolizumab. Treatment-related adverse events (TrAEs) were common, occurring in 15% of patients at grades 3 to 5 and 67% of patients at grades 1 to 2. Adverse events related to the immune system (IrAEs) were noted in 6% of individuals with grades (3-5) and 22% of patients with (grades 1-2). Serious adverse events occurred in 15% of patients overall; the atezolizumab group had a greater incidence (21%) than the pembrolizumab group (11%). Immune checkpoint inhibitors have shown encouraging effectiveness and safety in treating BCG-unresponsive NMIBC. However, the observed variability in therapeutic response and adverse events highlights the necessity for large-scale RCTs to clarify long-term efficacy and inform patient selection for ICI-based therapies.