Assessment of the external validity of the AJCC 8th staging system for small intestinal adenocarcinoma: a time to reconsider the role of tumor location?

Abstract

The current study evaluates the validity and performance of the 8th edition of the American Joint Committee on Cancer (AJCC) staging system for small intestinal adenocarcinoma patients. Surveillance, Epidemiology and End Results (SEER) database [2004-2015] was explored and AJCC 6th, 7th, and 8th 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. 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 6th stages were conducted and all P values for comparisons were significant (P<0.0001). Pairwise hazard ratio comparisons between different AJCC 7th and 8th 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 6th staging system was: 0.645 [standard error (SE): 0.011; 95% CI: 0.623-0.668]; for c-statistic for AJCC 7th staging system was 0.658 (SE: 0.011; 95% CI: 0.637-0.680); while c-statistic for AJCC 8th 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). There is no evidence that AJCC 8th 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.