Prognostic Validation of Perineural Invasion Severity Score in Pancreatic Cancer: A Prospective Study

Objective: This study aims to prospectively validate a perineural invasion (PNI) severity score in predicting recurrence and survival in resected PDAC. Background: PNI in pancreatic ductal adenocarcinoma (PDAC) is characterized by clinical and morphologic heterogeneity. Although a specific score for PNI severity has been proposed, it lacks validation. Methods: In this prospective registered (NCT04024358) monocentric study, 300 patients undergoing pancreatectomy between March 2019 and February 2022 were analyzed. PNI was scored as: 0 absent; 1 presence of neoplasia along nerves<3 mm; 2 neoplastic infiltration of nerves≥3 mm and/or massive PNI and/or necrosis of the infiltrated nerves. Association of PNI with disease recurrence and survival was evaluated. Results: Of 300 patients, 86% presented PNI, with 148 (49.3%) having PNI 1 and 110 (36.7%) PNI 2. Neoadjuvant treatment did not influence PNI (89.7% vs. 83.9% after treatment, P=0.332). PNI severity significantly correlated with worsening pathological features, shorter disease recurrence (24 mo for PNI 0, 17 for PNI 1 and 15 for PNI 2, P<0.01) and survival (57 mo for PNI 0, 51 for PNI 1 and 32 for PNI 2, P<0.01). PNI 2 independently predicted both recurrence and survival with HR of 2.082 (P=0.006) and 3.304 (P=0.014). PNI 2 benefitted most from adjuvant treatment, with longer disease recurrence time (17 vs. 12 mo; P=0.007) and survival (36 vs. 17 mo; P=0.004). Conclusions: The PNI severity score improves prognostic stratification of resected PDAC and identifies patients who benefit the most from adjuvant treatment.