Prognostic utility of perineural invasion in individuals with rectal cancer receiving neoadjuvant chemoradiotherapy: a meta-analysis.

OBJECTIVE: This study aimed to systematically examine the prognostic role of post-neoadjuvant chemoradiotherapy (nCRT) perineural invasion (yPNI) in patients with locally advanced rectal cancer (LARC) treated with nCRT. METHODS: This study was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. PubMed, Embase, Cochrane Library, Web of Science, China National Knowledge Infrastructure (CNKI), Wanfang Data, VIP Chinese Science and Technology Journal Database (VIP), and Chinese Biomedical Literature Database (SinoMed) were searched to identify eligible studies. Cohort studies that satisfied the inclusion criteria were included, and multivariable-adjusted effect sizes were extracted. The Newcastle-Ottawa Scale (NOS) was used to evaluate the quality of studies. Meta-analyses were carried out using STATA 15.1. RESULTS: A total of 36 studies involving 18,721 patients were included. The pooled prevalence of yPNI was 15.9%. Pooled results showed that yPNI was significantly associated with poorer overall survival (OS) (hazard ratio (HR) = 1.90, 95% confidence interval (CI): 1.63-2.21), recurrence-free survival (RFS) (HR = 1.96, 95% CI: 1.50-2.56), disease-free survival (DFS) (HR = 1.93, 95% CI: 1.55-2.42), cancer-specific survival (CSS) (HR = 1.98, 95% CI: 1.66-2.36), local recurrence-free survival (LRFS) (HR = 2.54, 95% CI: 1.86-3.48), and metastasis-free survival (MeFS) (HR = 2.82, 95% CI: 1.56-5.10). These findings suggested that yPNI-positive patients had a higher risk of recurrence and death. Sensitivity analyses further validated the robustness of the findings. CONCLUSION: yPNI was associated with adverse survival outcomes in patients with LARC treated with nCRT. Further studies are needed to determine whether yPNI provides additional prognostic information beyond established clinicopathological factors. SYSTEMATIC REVIEW REGISTRATION: https://www.crd.york.ac.uk/PROSPERO/view/CRD420251230519, identifier CRD420251230519.