The impact of perineural invasion on prognosis in esophageal cancer patients after surgery: a systematic review and meta-analysis

Objective: This study aims to update the prognostic value of perineural invasion(PNI) in various subgroups of esophageal cancer patients. Methods: We searched databases including PubMed, Scopus, Wiley, Web of Science, and Embase for full-text articles published in English on esophageal cancer related to PNI. The search was conducted up to January 1, 2024. We summarized the hazard ratios (HR) and 95% confidence intervals (CI) for overall survival (OS), disease-free survival (DFS), as well as recurrence and metastasis, to assess the prognostic value of PNI in patients with esophageal cancer. Results: A total of 38 eligible studies were ultimately included. Thirty-two studies, encompassing a total of 7157 patients, reported the correlation between PNI and OS. The results indicated that PNI is significantly associated with poor OS in esophageal cancer patients (HR = 1.54, 95% CI: 1.41-1.68, P < 0.00001). Eleven studies, including a total of 2224 patients, reported the correlation between PNI and DFS. These studies found that PNI is significantly associated with poor DFS (HR = 1.43, 95% CI: 1.25-1.62, P < 0.00001). Three studies, including a total of 1125 patients, reported no correlation between PNI and recurrence (HR = 1.17, 95% CI: 0.62-2.18, P = 0.63). Two studies, including a total of 556 patients, reported a correlation between PNI and distant metastasis (HR = 2.19, 95% CI: 1.02-4.73, P = 0.04). Further subgroup analysis revealed that PNI is an independent prognostic factor for esophageal squamous cell carcinoma (ESCC) (OS: HR=1.62, 95%CI: 1.35-1.94, P<0.00001; DFS: HR=1.28, 95%CI: 1.03-1.59, P=0.03); however, in esophageal adenocarcinoma, PNI is not associated with OS or DFS (OS: HR=1.23, 95%CI: 1.00-1.53, P=0.05; DFS: HR=1.65, 95%CI: 0.95-2.87, P=0.08). PNI positivity is associated with unfavorable outcomes, irrespective of neoadjuvant therapy receipt. In the non-Asian subgroup, PNI is not statistically significant for poor DFS prognosis. Conclusion: PNI is a histological marker of aggressive disease and can serve as an independent prognostic factor for patients with esophageal cancer. PNI positivity can predict poor outcomes in ESCC, but its role as a prognostic indicator for adenocarcinoma requires further investigation.