Neoadjuvant chemoradiotherapy with or without preoperative immunotherapy for locally advanced rectal cancer: a system review and meta-analysis.

For locally advanced rectal cancer (LARC), adding immunotherapy after patients receive standard neoadjuvant chemoradiotherapy (nCRT) or short-course radiotherapy (SCRT) is a new method. This study aims to evaluate the efficacy and safety of the combination of nCRT/SCRT and immunotherapy on LARC patients based on the current published studies. A comprehensive electronic search of literature up to December 1, 2024 was carried out in Pubmed, the Cochrane Library, Web of Science, Google Scholar databases and Embase. Studies comparing the nCRT/SCRT with preoperative immunotherapy (nCRT/SCRT + IMT group) and nCRT/SCRT alone (nCRT/SCRT group) were included. The primary outcome was the pathological complete response (pCR) rate. Three randomized control trials and one retrospective study, involving 692 LARC patients, were included. The pooled pCR rate was 40.6% (134/330) in the nCRT/SCRT + IMT group and 22.5% (66/293) in the nCRT/SCRT group (RR = 1.68, 95% CI 1.11-2.55, p = 0.01). The pTRG 0-1 rate was 69.0% (180/261) in the nCRT/SCRT + IMT group and 47.1% (106/225) in the nCRT/SCRT group (RR = 1.43, 95% CI 1.22-1.68, p < 0.001). The major adverse events rate (grade 3-4) were comparable between the nCRT/SCRT + IMT group and the nCRT/SCRT group (61/194, 31.4% vs 51/197, 25.9%, RR = 1.22, 95% CI 0.90-1.65; P = 0.20). Preoperative immunotherapy in combination with standard nCRT/SCRT may improve the tumor regression and increase the pCR rate in selected LARC patients without additional major treatment adverse events.