The impact of molecular subtyping on pathological staging of pancreatic cancer

Dreyer, S. B. et al. (2021) The impact of molecular subtyping on pathological staging of pancreatic cancer. Annals of Surgery, (doi: 10.1097/SLA.0000000000005050) (Early Online Publication)

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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 sub-optimal 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.

Item Type:Articles
Additional Information:Funding: Wellcome Trust Senior Investigator Award: 103721/Z/14/Z, Cancer Research UK Programme: C29717/A17263 and C29717/A18484, Cancer Research UK Glasgow Centre: C596/A18076, Cancer Research UK Clinical Training Award: C596/A20921, Cancer Research UK Clinician Scientist Award: C55370/A25813, The National Health and Medical Research Council of Australia, The Cancer Council NSW, Cancer Institute NSW, Royal Australasian College of Surgeons, St Vincent’s Clinic Foundation and R. T. Hall Trust, The Australian Pancreatic Cancer Foundation, Associazione Italiana Ricerca Cancro (AIRC 5x1000 n. 12182), Fondazione Italiana Malattie Pancreas – Ministero Salute [FIMPCUP_J38D19000690001], Fondazione Cariverona: Oncology Biobank Project “Antonio Schiavi” (prot. 203885/2017), IG2020-24393-Associazione Italiana per la Ricerca su Cancro.
Status:Early Online Publication
Refereed:Yes
Glasgow Author(s) Enlighten ID:Jamieson, Dr Nigel and Dreyer, Dr Stephan and Biankin, Professor Andrew and pea, Dr Antonio and Gemenetzis, Mr Georgios and Upstill-Goddard, Dr Rosie and Duthie, Dr Fraser and McKay, Mr Colin and Chang, Professor David
Authors: Dreyer, S. B., Rae, S., Bisset, K., Upstill-Goddard, R., Gemenetzis, G., Johns, A. L., Australian Pancreatic Cancer Genome Initiative3,, , Glasgow Precision Oncology Laboratory1, , Dickson, E. J., Mittal, A., Gill, A. J., Duthie, F., pea, A., Lawlor, R. T., Scarpa, A., Salvia, R., Pulvirenti, A., Zerbi, A., Marchesi, F., McKay, C. J., Biankin, A. V., Samra, J. S., Chang, D. K., and Jamieson, N. B.
College/School:College of Medical Veterinary and Life Sciences > School of Cancer Sciences
Journal Name:Annals of Surgery
Publisher:Lippincott, Williams and Wilkins
ISSN:0003-4932
ISSN (Online):1528-1140
Published Online:12 July 2021

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
170634Defining Platinum and PARP Responsive Molecular Phenotypes of Pancreatic Cancer.Andrew BiankinWellcome Trust (WELLCOTR)103721/Z/14/ZInstitute of Cancer Sciences
169396Genotype Guided Stratified Therapy for Pancreatic CancerAndrew BiankinCancer Research UK (CRUK)C29717/A17263Institute of Cancer Sciences
190874CR-UK Centre renewalKaren VousdenCancer Research UK (CRUK)C596/A18076Institute of Cancer Sciences
172008Clinical Training Award Cycle 2Andrew BiankinCancer Research UK (CRUK)C596/A20921CS -Translational Research Centre
301364COMBINATION THERAPIES TARGETING IMMUNE EVASION IN PANCREATIC CANCERNigel JamiesonCancer Research UK (CRUK)C55370/A25813CS -Translational Research Centre