The Impact of Molecular Subtyping on Pathological Staging of Pancreatic Cancer.

Abstract

BACKGROUND:

The 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.

OBJECTIVE:

The aim of this study was to evaluate traditional staging criteria for PDAC in the setting of molecular subtypes.

METHODS:

Clinicopathological 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.

RESULTS:

TNM 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.

CONCLUSIONS:

Aggressive tumor biology as measured by molecular subtype predicts poor outcome following pancreatectomy for PDAC and should be utilized to inform patient selection for surgery.

• Authors: 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, Glasgow Precision Oncology Laboratory
• Journal: Annals of surgery (Ann Surg) Vol. 277 Issue 2 Pg. e396-e405 (02 01 2023) ISSN: 1528-1140 [Electronic] United States
• PMID: 36745763 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc.

Topics

• Humans
• Pancreatic Neoplasms (pathology)
• Prognosis
• Carcinoma, Pancreatic Ductal (pathology)
• Pancreatectomy
• Neoplasm Staging
• Carcinoma, Squamous Cell (surgery)
• Retrospective Studies
• Survival Rate
• Pancreatic Neoplasms