The Impact of Molecular Subtyping on Pathological Staging of Pancreatic Cancer.
Journal
Annals of surgery
ISSN: 1528-1140
Titre abrégé: Ann Surg
Pays: United States
ID NLM: 0372354
Informations de publication
Date de publication:
01 02 2023
01 02 2023
Historique:
entrez:
6
2
2023
pubmed:
7
2
2023
medline:
9
2
2023
Statut:
ppublish
Résumé
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. The aim of this study was to evaluate traditional staging criteria for PDAC in the setting of molecular subtypes. 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. 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. 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.
Sections du résumé
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.
Identifiants
pubmed: 36745763
doi: 10.1097/SLA.0000000000005050
pii: 00000658-202302000-00049
pmc: PMC9831035
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e396-e405Subventions
Organisme : Pancreatic Cancer UK
ID : FLF2015_04_GLASGOW
Pays : United Kingdom
Informations de copyright
Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc.
Déclaration de conflit d'intérêts
The authors report no conflicts of interest.
Références
Mol Cancer. 2017 Nov 6;16(1):168
pubmed: 29110659
Nat Rev Gastroenterol Hepatol. 2019 Apr;16(4):207-220
pubmed: 30718832
Clin Oncol (R Coll Radiol). 2020 Jan;32(1):1-4
pubmed: 31378449
Br J Surg. 2018 Jan;105(2):e183-e191
pubmed: 29341146
Ann Surg. 2017 Jan;265(1):185-191
pubmed: 27163957
Nature. 2016 Mar 3;531(7592):47-52
pubmed: 26909576
J Gastrointest Surg. 2013 Mar;17(3):511-21
pubmed: 23297028
J Gastrointest Oncol. 2017 Aug;8(4):683-695
pubmed: 28890819
BMC Bioinformatics. 2020 Jan 28;21(1):30
pubmed: 31992186
Nat Cancer. 2020 Jan;1(1):59-74
pubmed: 35118421
Nat Med. 2011 Apr;17(4):500-3
pubmed: 21460848
Nat Commun. 2018 Jun 20;9(1):2419
pubmed: 29925878
Proc Natl Acad Sci U S A. 2019 Dec 26;116(52):26835-26845
pubmed: 31843922
Gut. 2020 Feb;69(2):317-328
pubmed: 31201285
Ann Surg. 2017 Mar;265(3):565-573
pubmed: 27918310
Ann Surg. 2010 Jun;251(6):1003-10
pubmed: 20485150
Pancreatology. 2018 Jan;18(1):2-11
pubmed: 29191513
Gastroenterology. 2018 Dec;155(6):1999-2013.e3
pubmed: 30165049
JAMA. 2010 Sep 8;304(10):1073-81
pubmed: 20823433
CA Cancer J Clin. 2018 Jan;68(1):7-30
pubmed: 29313949
Nat Genet. 2020 Feb;52(2):231-240
pubmed: 31932696
Lancet. 2017 Mar 11;389(10073):1011-1024
pubmed: 28129987
Nature. 2015 Feb 26;518(7540):495-501
pubmed: 25719666
Ann Surg. 2019 Mar;269(3):520-529
pubmed: 29068800
Ann Surg Oncol. 2012 Oct;19(11):3581-90
pubmed: 22555345
J Clin Oncol. 2009 Jun 10;27(17):2855-62
pubmed: 19398572
Cancer Res. 2014 Jun 1;74(11):2913-21
pubmed: 24840647
Nature. 2010 Apr 15;464(7291):993-8
pubmed: 20393554
Br J Cancer. 2008 Feb 12;98(3):537-41
pubmed: 18231110
Ann Surg. 2019 May;269(5):944-950
pubmed: 29334560
Nat Genet. 2015 Oct;47(10):1168-78
pubmed: 26343385
Proc Natl Acad Sci U S A. 2012 Apr 17;109(16):5934-41
pubmed: 22421440
Clin Cancer Res. 2018 Mar 15;24(6):1344-1354
pubmed: 29288237
Gastroenterology. 2009 Aug;137(2):558-68, 568.e1-11
pubmed: 19376121
Nature. 2012 Nov 15;491(7424):399-405
pubmed: 23103869
Ann Surg. 2020 Aug;272(2):366-376
pubmed: 32675551
JAMA Surg. 2018 Dec 1;153(12):e183617
pubmed: 30285076
Ann Surg. 2022 Jan 1;275(1):175-181
pubmed: 32149822
Ann Surg Oncol. 2021 Aug;28(8):4602-4612
pubmed: 33393031