Neoadjuvant therapy combined with immunotherapy for anal sphincter preservation rate, clinical efficacy, and safety in rectal cancer patients: a meta-analysis.

Background: Neoadjuvant therapy combined with immunotherapy has emerged as a promising strategy for rectal cancer (RC), but its efficacy in anal sphincter preservation, clinical outcomes, and safety profile remains to be systematically validated. This meta-analysis aims to comprehensively evaluate the anal sphincter preservation rate, clinical efficacy, and safety of neoadjuvant therapy combined with immunotherapy in rectal cancer patients, providing evidence-based support for clinical decision-making. Objective: To assess the anal sphincter preservation rate, key clinical efficacy indicators (including pathological complete response rate, R0 resection rate, and tumor regression grade), and safety indicators (adverse events and postoperative complications) of neoadjuvant therapy combined with immunotherapy in rectal cancer patients. We systematically synthesize the absolute sphincter-preservation, pathological-response, and safety proportions of neoadjuvant immunotherapy in rectal cancer patients, with any comparison to historical data of conventional regimens presented as indirect and exploratory only. Methods: This study was prospectively registered in PROSPERO (registration number: CRD420251159170) and reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The methodological quality of this systematic review was evaluated using the AMSTAR 2 tool. A comprehensive electronic search was performed across eight databases (PubMed, Embase, Cochrane Library, Web of Science, Sinomed, CNKI, WanFang, and VIP) up to February 2, 2026. Eligible studies included randomized controlled trials (RCTs), single-arm trials, and observational studies (cohort studies, case-control studies) investigating neoadjuvant therapy combined with immunotherapy for rectal cancer. Data extraction was independently performed by two authors, and risk of bias was assessed using the ROBINS-I tool (for non-randomized studies) and the Cochrane Collaboration risk of bias tool (for RCTs). The GRADE approach was used to evaluate the certainty of evidence. Statistical analysis was conducted with R Studio 4.3.2 software, employing random-effects or fixed-effects models based on heterogeneity (assessed by I² statistic and chi-squared test). This meta-analysis does not include controlled comparative trials and that all analyses are single-arm proportion pooling without direct between-group comparisons. Results: A total of 16 studies involving 540 rectal cancer patients were included. The pooled anal sphincter preservation rate was 0.90 (95% CI: 0.87-0.93) with moderate heterogeneity (I²=37.4%, P = 0.0716). The R0 resection rate was 0.98 (95% CI: 0.96-1.00) (I²=51.4%, Conclusions: Neoadjuvant therapy combined with immunotherapy was associated with favorable pooled proportions of sphincter preservation and R0 resection in the included studies, although these estimates are derived predominantly from single-arm studies. This regimen warrants further investigation for organ preservation strategies, but confirmatory evidence from high-quality RCTs is needed. Given that the current evidence is predominantly of low-to-moderate certainty, high-quality, large-scale RCTs with long-term follow-up are needed to further validate these findings and optimize treatment regimens. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=CRD420251159170, identifier CRD420251159170.