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

Abstract

This study aims to prospectively validate a perineural invasion (PNI) severity score in predicting recurrence and survival in resected PDAC. 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. 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. 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). The PNI severity score improves prognostic stratification of resected PDAC and identifies patients who benefit the most from adjuvant treatment.