The Impact of Molecular Subtyping on Pathological Staging of Pancreatic Cancer

Ann Surg. 2023 Feb 1;277(2):e396-e405. doi: 10.1097/SLA.0000000000005050. Epub 2023 Jan 10.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

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