• Stephan B Dreyer, Sarah Rae, Kirsty Bisset, Rosie Upstill-Goddard, Georgios Gemenetzis, Amber L Johns, Euan J Dickson, Anubhav Mittal, Anthony J Gill, Fraser Duthie, Antonio Pea, Rita T Lawlor, Aldo Scarpa, Roberto Salvia, Alessandra Pulvirenti, Alessandro Zerbi, Federica Marchesi, Colin J McKay, Andrew V Biankin, Jaswinder S Samra, David K Chang, Nigel B Jamieson, Australian Pancreatic Cancer Genome Initiative, and Glasgow Precision Oncology Laboratory.
• Wolfson Wohl Cancer Research Centre, Institute of Cancer Sciences, University of Glasgow, Garscube Estate, Switchback Road, Bearsden, Glasgow, Scotland, United Kingdom.
• Ann. Surg. 2023 Feb 1; 277 (2): e396e405e396-e405.

BackgroundThe long-term outcomes following surgical resection for pancreatic ductal adenocarcinoma (PDAC) remains poor, with only 20% of patients surviving 5 years after pancreatectomy. Patient selection for surgery remains suboptimal largely due to the absence of consideration of aggressive tumor biology.ObjectiveThe aim of this study was to evaluate traditional staging criteria for PDAC in the setting of molecular subtypes.MethodsClinicopathological data were obtained for 5 independent cohorts of consecutive unselected patients, totaling n = 1298, including n = 442 that underwent molecular subtyping. The main outcome measure was disease-specific survival following surgical resection for PDAC stratified according to the American Joint Commission for Cancer (TNM) staging criteria, margin status, and molecular subtype.ResultsTNM staging criteria and margin status confers prognostic value only in tumors with classical pancreatic subtype. Patients with tumors that are of squamous subtype, have a poor outcome irrespective of favorable traditional pathological staging [hazard ratio (HR) 1.54, 95% confidence interval (CI) 1.04-2.28, P = 0.032]. Margin status has no impact on survival in the squamous subtype (16.0 vs 12.1 months, P = 0.374). There were no differences in molecular subtype or gene expression of tumors with positive resection margin status.ConclusionsAggressive tumor biology as measured by molecular subtype predicts poor outcome following pancreatectomy for PDAC and should be utilized to inform patient selection for surgery.Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc.

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