Direct Nodal Invasion Is Associated with Improved Survival Compared with Nodal Metastasis in AJCC N1 PDAC.

Abstract

Introduction: Pancreatic ductal adenocarcinoma (PDAC) prognosis is strongly influenced by nodal disease, however the AJCC 8th edition classifies nodal disease solely by the number of involved nodes, without accounting for the mechanism of involvement. Direct tumour extension into adjacent lymph nodes may represent a biologically distinct process from true lymphatic metastasis, but this distinction is not captured in current staging systems. Method(s): A multicentre retrospective cohort study was conducted using the Upper Gastrointestinal Cancer Registry across five tertiary centres in Melbourne, Australia. Patients undergoing resection for AJCC N1 PDAC (1-3 positive nodes) between 2009 and 2024 were included. Nodal involvement was classified as direct invasion (contiguous tumour extension) or true metastasis (non-contiguous involvement) based on detailed review of synoptic and narrative pathology reports. Recurrence-free survival (RFS) and overall survival (OS) were analysed using multivariable Cox regression adjusting for tumour stage, perineural and lymphovascular invasion, margin status, tumour size, and adjuvant chemotherapy. Result(s): Among 120 patients, 18.3% demonstrated direct nodal invasion. Compared with true nodal metastasis, direct invasion was independently associated with improved RFS (adjusted HR 0.34, 95%CI 0.13-0.89, p=0.029) and OS (adjusted HR 0.44, 95%CI 0.21-0.92, p=0.029). These findings were independent of established pathological and treatment-related prognostic factors. Conclusion(s): Direct nodal invasion in PDAC is associated with improved oncological outcomes compared with true nodal metastasis, despite equivalent AJCC staging. These findings suggest that the mechanism of nodal involvement conveys independent prognostic information and represents an unrecognised source of heterogeneity within N1 disease. Incorporation of nodal invasion patterns into future staging systems warrants consideration. [Formula presented] * Oral Poster & Electronic Poster presented.Copyright © 2026