Perineural Invasion is an Important Prognostic Factor in Patients With Radically Resected (R0) and Node-negative (pN0) Pancreatic Cancer

OBJECTIVE: To investigate the association between perineural invasion (PNI) and overall survival (OS) in a nationwide cohort of patients with resected pancreatic ductal adenocarcinoma (PDAC), stratified for margin negative (R0) or positive (R1) resection and absence or presence of lymph node metastasis (pN0 or pN1-pN2, respectively). BACKGROUND: Patients with R0 and pN0 resected PDAC have a relatively favorable prognosis. As PNI is associated with worse OS, this might be a useful factor to provide further prognostic information for patients counselling. METHODS: A nationwide observational cohort study was performed including all patients who underwent PDAC resection in the Netherlands (2014-2019) with complete information on relevant pathologic features (PNI, R status, and N status). OS was assessed using Kaplan-Meier curves, and Cox-proportional hazard analyses were performed to calculate hazard ratios (HRs) with corresponding 95% CIs. RESULTS: In total, 1630 patients were included with a median follow-up of 43 (interquartile range: 33-58) months. PNI was independently associated with worse OS in both R0 patients [HR: 1.49 (95% CI: 1.18-1.88); P < 0.001] and R1 patients [HR: 1.39 (95% CI: 1.06-1.83); P = 0.02], as well as in pN0 patients [HR: 1.75 (95% CI: 1.27-2.41); P < 0.001] and pN1-N2 patients [HR: 1.35 (95% CI: 1.10-1.67); P < 0.01]. In 315 patients with R0N0, multivariable analysis showed that PNI was the strongest predictor of OS [HR: 2.24 (95% CI: 1.52-3.30); P < 0.001]. CONCLUSIONS: PNI is strongly associated with worse survival in patients with resected PDAC, in particular in patients with relatively favorable pathologic features. These findings may aid patient stratification and counseling and help guide treatment strategies.