Abstract
BACKGROUND: Immunotherapy is an approved treatment for metastatic rectal cancer in patients with defective mismatch repair (MMR). AIM: To examine the clinical efficacy of neoadjuvant immunotherapy combined with radiotherapy and chemotherapy for the treatment of locally advanced rectal cancer (LARC), with a focus on patients with proficient MMR (pMMR) and microsatellite stability. METHODS: Two researchers searched multiple databases for publications up to September 2024. All included publications examined neoadjuvant immunotherapy for LARC, and reported major pathological response (MPR), pathological complete response (pCR), clinical complete response (CCR), and rates of R0 resection and anus-preserving surgery. Meta-analysis, subgroup analysis, sensitivity analysis, and analysis of publication bias were performed. RESULTS: We included 15 publications (796 patients). The MPR, pCR, and CCR were significantly better in the group that received immunotherapy (all P < 0.05), especially for patients with pMMR. In addition, the rate of R0 resection and anus-preserving surgery were also significantly greater in the group that received neoadjuvant immunotherapy (both P < 0.05). Hematological toxicity and abnormal liver function were the most common clinical adverse events above grade 3. Most patients successfully completed the immunotherapy treatment. The incidence of immune-related adverse reactions was 0%-13.5%, and the severities of these events were generally considered acceptable. CONCLUSION: The addition of neoadjuvant immunotherapy improved the clinical remission rate of patients who had LARC with pMMR, and the treatment-related adverse reactions were generally acceptable. Neoadjuvant immunotherapy combined with radiotherapy and chemotherapy should be considered for patients with LARC.