Abstract
BACKGROUND: The current study evaluates the validity and performance of the 8(th) edition of the American Joint Committee on Cancer (AJCC) staging system for small intestinal adenocarcinoma patients. METHODS: Surveillance, Epidemiology and End Results (SEER) database [2004-2015] was explored and AJCC 6(th), 7(th), and 8(th) versions were assigned for each patient. Through Kaplan-Meier estimates, overall survival analyses were conducted. Cox regression analysis (adjusted for age, race, gender, sub-site, grade and surgical treatment) was conducted for cancer-specific survival and additionally, pairwise hazard ratio comparisons were performed. RESULTS: A total of 2,997 small intestinal adenocarcinoma patients were eligible and included in the analysis. Overall survival was compared according to the three AJCC staging systems. For the three versions, the P value for the trend in overall survival was significant (P<0.0001). Cancer-specific Cox regression hazard was calculated for the three staging systems. Pairwise hazard ratio comparisons between different AJCC 6(th) stages were conducted and all P values for comparisons were significant (P<0.0001). Pairwise hazard ratio comparisons between different AJCC 7(th) and 8(th) stages were also performed, and all comparisons were significant (P<0.05) except for stage IIB vs. IIIA. C-statistic (using death from small intestinal adenocarcinoma as the dependent variable) for AJCC 6(th) staging system was: 0.645 [standard error (SE): 0.011; 95% CI: 0.623-0.668]; for c-statistic for AJCC 7(th) staging system was 0.658 (SE: 0.011; 95% CI: 0.637-0.680); while c-statistic for AJCC 8(th) staging system was 0.660 (SE: 0.011; 95% CI: 0.638-0.682). Multivariate analysis of factors affecting cancer-specific survival suggested that older age (P=0.005), higher lymph node ratio (P<0.0001) and duodenal localization of the primary are associated with worse outcomes (P=0.008). CONCLUSIONS: There is no evidence that AJCC 8(th) system provided better prognostic characterization compared to previous AJCC staging systems for small intestinal adenocarcinoma. Subsite-specific staging paradigms should be explored in future editions of the staging system.