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

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.

The diversity between curatively resected pancreatic head and body-tail cancers based on the 8th edition of AJCC staging system: a multicenter cohort study

“…consecutive patients, the new T stage does not demonstrate significant correlation with survival on univariate or multivariate analysis, whereas the new N stage showed accurate discrimination of survival [12]. These results were consistent with our current study.…”

Prognostic and predictive factors in pancreatic cancer

“…In patients undergoing surgery, the histological analysis defines the pathological stage according to the 8 th edition of the TNM system [7]. The TNM staging system relies on its reproducibility using anatomic parameters to stratify patients with different survival outcomes [8]. Differently from the 7th edition, the current TNM system does not consider the extension outside the pancreas as T3, because staging in the T stage has been replaced by a size-based system [8].…”

“…The TNM staging system relies on its reproducibility using anatomic parameters to stratify patients with different survival outcomes [8]. Differently from the 7th edition, the current TNM system does not consider the extension outside the pancreas as T3, because staging in the T stage has been replaced by a size-based system [8]. The N (nodes) parameter has been divided in N1 and N2 depending on the number of positive regional lymph nodes.…”

Treatment and Survival of Elderly Patients with Stage I–II Pancreatic Cancer: A Report of the EURECCA Pancreas Consortium

“…Second, the 7th edition, rather than the 8th edition, of the TNM classification was used in the analyses due to data availability. As shown by external validation studies, the 8th edition has more prognostic significance, 39,40 but, on the other hand, was not yet in use during the study period (2012-2016). Third, this study included adjusted analyses for age group, but, nevertheless, residual confounding cannot be ruled out.…”