Comparative efficacy and safety of treatment options for BCG unresponsive bladder cancer: A systematic review

Background: Non-muscle-invasive bladder cancer (NMIBC) patients who do not respond to Bacillus Calmette-Guérin (BCG) therapy face significant challenges in disease management. Even though BCG is the mainstay of treatment, up to 50% of patients do not response, requiring the use of alternate therapeutic approaches. Objectives: The systematic review aim to summarize and synthesize the evidence from existing studies on the safety and effectiveness of treatments for BCG-unresponsive NMIBC without performing indirect comparisons or rankings. Methods: A comprehensive literature search was undertaken using PRISMA principles across databases such as PubMed and Cochrane Library. The study includes randomized controlled trials (RCTs) published between 2014 and 2024 that focused on immune checkpoint inhibitors, intravenous chemotherapy, and combination therapies. Complete response (CR) rates were used to quantify efficacy, whereas adverse events (AEs) were used to assess safety. Results: The analysis comprised 10 RCTs. Pembrolizumab had a CR rate of 38.8%, Nadofaragene firadenovec 53.4%, and gemcitabine plus docetaxel 47%. Gemcitabine had the greatest safety profile, with the fewest adverse events, but pembrolizumab was linked with controllable immune-related adverse events. Conclusion: Pembrolizumab and Nadofaragene firadenovec are potential treatment options for BCG-unresponsive NMIBC. Gemcitabine and docetaxel combinations are excellent options, especially for individuals who cannot tolerate systemic treatments. Personalized techniques and long-term research are critical for improving patient treatment.