Perineural Invasion in Pancreatic Ductal Adenocarcinoma: Recapitulating Its Importance and Defining Future Directions

Pancreatic ductal adenocarcinoma (PDAC) remains one of the most lethal malignancies, mainly due to its aggressive nature, early metastasis, diagnosis at late stages, and limited response to systemic anticancer therapy. Perineural invasion (PNI), defined as the infiltration of neoplastic cells along nerve fibers and within nerve sheaths, is emerging as a critical determinant of PDAC aggressiveness. This position paper by the TRANSPAN PNI Group on Perineural Invasion synthesizes current evidence on the molecular features and clinical implications of PNI in PDAC, compares its prognostic significance in other malignancies, and describes novel biomarker strategies including potential therapeutic interventions.