Immune-related adverse events associated with immune checkpoint inhibitor therapy in bladder cancer patients: A systematic review and meta-analysis.

Immune-related adverse events (irAEs) are commonly associated with immune checkpoint inhibitor (ICI) therapy. ICIs are recommended at various stages of bladder cancer treatment, and appropriate management of irAEs is important in improving long-term outcomes in bladder cancer. This systematic review and meta-analysis of randomized controlled trials (RCTs) aims to assess irAEs associated with ICI therapy in bladder cancer. A comprehensive literature search was conducted across PubMed/MEDLINE, Embase, Web of Science, Cochrane Library, and Epistemonikos from inception till January 2025. The references of the included studies, clinicaltrials.gov, annual meeting abstracts of ASCO and ESMO, and the WHO International Clinical Trials Registry Platform were also searched for additional studies. Phase II or III randomized controlled trials (RCTs) where one of the experimental arms consisted of atezolizumab, pembrolizumab, nivolumab, or avelumab monotherapy were included. A Random effects model was used to conduct the meta-analysis in R Statistical Software, version 4.3.3. From the initial 1,092 articles screened, 12 were included in the systematic review and meta-analysis, comprising a total of 7,333 patients. Hypothyroidism (RR: 5.87 (3.23, 10.67)), hyperthyroidism (RR: 11.05 (4.20, 29.03)), pruritus (RR: 4.95 (2.82, 8.70)), rash (RR: 2.92 (1.51, 5.64)), colitis (RR: 2.15 (1.11, 4.15)), pneumonitis (RR: 3.91 (2.18, 7.02)), and nephritis (RR: 4.97 (1.43, 17.33)) were found to be significant irAEs associated with ICI therapy. Bladder cancer patients treated with ICIs are at significant risk of irAEs. These events vary in severity, and appropriate management of these adverse events should be prioritized to improve quality of life.