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Original Investigation
December 19, 2018

International Validation of the Eighth Edition of the American Joint Committee on Cancer (AJCC) TNM Staging System in Patients With Resected Pancreatic Cancer

Author Affiliations
  • 1Department of Surgery, Cancer Center Amsterdam, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands
  • 2Surgical Outcomes Analysis and Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts
  • 3Department of Pathology, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands
  • 4Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts
  • 5Department of Surgery, Pancreas Institute, Verona University Hospital, Verona, Italy
  • 6Department of Surgery, Boston Medical Center, Boston University School of Medicine, Boston, Massachusetts
  • 7Department of Surgery, Southampton University Hospital National Health Service Foundation Trust, Southampton, United Kingdom
  • 8Department of Surgery, Erasmus MC, Rotterdam, the Netherlands
JAMA Surg. 2018;153(12):e183617. doi:10.1001/jamasurg.2018.3617
Key Points

Question  What is the incremental value in prognostic accuracy of the American Joint Committee on Cancer eighth edition of the TNM staging system in resected pancreatic cancer, compared with the seventh edition?

Findings  In this cohort study of 1525 patients with resected pancreatic cancer from Europe and the United States, the eighth edition of the TNM staging system demonstrated a concordance statistic of 0.57, compared with 0.55 via the seventh edition. The revised T stage alone does not add to the discriminatory power, whereas the revised N stage is highly prognostic.

Meaning  The eighth edition of the TNM staging system provides additional prognostic accuracy in patients with resected pancreatic cancer compared with the seventh edition.

Abstract

Importance  The recently released eighth edition of the American Joint Committee on Cancer TNM staging system for pancreatic cancer seeks to improve prognostic accuracy but lacks international validation.

Objective  To validate the eighth edition of the American Joint Committee on Cancer TNM staging system in an international cohort of patients with resected pancreatic ductal adenocarcinoma.

Design, Setting, and Participants  This international multicenter cohort study took place in 5 tertiary centers in Europe and the United States from 2000 to 2015. Patients who underwent pancreatoduodenectomy for nonmetastatic pancreatic ductal adenocarcinoma were eligible. Data analysis took place from December 2017 to April 2018.

Exposures  Patients were retrospectively staged according to the seventh and eighth editions of the TNM staging system.

Main Outcomes and Measures  Prognostic accuracy on survival rates, assessed by Kaplan-Meier and multivariate Cox proportional hazards analyses and concordance statistics.

Results  A total of 1525 consecutive patients were included (median [IQR] age, 66 (58-72) years; 802 (52.6%) male). Distribution among stages via the seventh edition was stage IA in 41 patients (2.7%), stage IB in 42 (2.8%), stage IIA in 200 (13.1%), stage IIB in 1229 (80.6%), and stage III in 12 (0.8%); this changed with use of the eighth edition to stage IA in 118 patients (7.7%), stage IB in 144 (9.4%), stage IIA in 22 (1.4%), stage IIB in 643 (42.2%), and stage III in 598 (39.2%). With the eighth edition, 774 patients (50.8%) migrated to a different stage; 183 (12.0%) were reclassified to a lower stage and 591 (38.8%) to a higher stage. Median overall survival for the entire cohort was 24.4 months (95% CI, 23.4-26.2 months). On Kaplan-Meier analysis, 5-year survival rates changed from 38.2% for patients in stage IA, 34.7% in IB, 35.3% in IIA, 16.5% in IIB, and 0% in stage III (log-rank P < .001) via classification with the seventh edition to 39.2% for patients in stage IA, 33.9% in IB, 27.6% in IIA, 21.0% in IIB, and 10.8% in stage III (log-rank P < .001) with the eighth edition. For patients who were node negative, the T stage was not associated with prognostication of survival in either edition. In the eighth edition, the N stage was associated with 5-year survival rates of 35.6% in N0, 20.8% in N1, and 10.9% in N2 (log-rank P < .001). The C statistic improved from 0.55 (95% CI, 0.53-0.57) for the seventh edition to 0.57 (95% CI, 0.55-0.60) for the eighth edition.

Conclusions and Relevance  The eighth edition of the TNM staging system demonstrated a more equal distribution among stages and a modestly increased prognostic accuracy in patients with resected pancreatic ductal adenocarcinoma compared with the seventh edition. The revised T stage remains poorly associated with survival, whereas the revised N stage is highly prognostic.

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