Surgical safety of preoperative or perioperative immune checkpoint inhibitors in colorectal cancer surgery: protocol for a systematic review and meta-analysis focusing on anastomotic leakage.

INTRODUCTION: Immune checkpoint inhibitors (ICIs) are increasingly used before colorectal cancer surgery, particularly for mismatch repair-deficient or microsatellite instability-high tumours. Their surgery-specific safety, especially the risk of anastomotic leakage (AL), remains uncertain. We aim to synthesise AL and other postoperative outcomes after preoperative or perioperative ICI therapy. METHODS AND ANALYSIS: We will search PubMed/MEDLINE, Embase, Web of Science, Scopus, CENTRAL, ClinicalTrials.gov, CNKI and the WHO International Clinical Trials Registry Platform from inception to July 2026 without language restrictions. We will include randomised and non-randomised comparative studies, cohort and case-control studies and single-arm studies reporting postoperative outcomes after preoperative or perioperative ICI therapy; case reports and case series with fewer than five surgically treated patients will be excluded. The primary outcome is AL among patients who underwent bowel resection with a constructed intestinal anastomosis. Two reviewers will independently screen records, extract data and assess risk of bias using design-appropriate validated tools. Comparative and non-comparative studies will be analysed separately: risk ratios from comparative studies will be pooled in random-effects models, and single-arm AL rates will be pooled as proportions using a binomial-logit generalised linear mixed model. Heterogeneity, prespecified subgroup analyses, sensitivity analyses and the certainty of the evidence (Grading of Recommendations Assessment, Development and Evaluation) will be reported. ETHICS AND DISSEMINATION: Ethics approval is not required because only published aggregate data will be used. Results will be submitted to a peer-reviewed journal and presented at scientific meetings. Extraction materials, analytical code and the derived dataset will be shared in an open repository with the completed review. PROSPERO REGISTRATION NUMBER: CRD420261426134.