Validation of the 8th Edition American Joint Commission on Cancer (AJCC) Gallbladder Cancer Staging System: Prognostic Discrimination and Identification of Key Predictive Factors

SIMPLE SUMMARY: Despite implementing numerous changes in the American Joint Committee on Cancer (AJCC) staging system for gallbladder cancer (GBC), the ability to accurately prognosticate survival in these patients has not been vigorously evaluated. The purpose of our study was to compare the prognostic ability of AJCC 7th and 8th edition, investigate the effect of AJCC 8th edition nodal status on the survival, and identify risk factors associated with the survival after N reclassification in GBC patients. We used the largest cancer database in the United States and determined that the updated AJCC 8th edition GBC staging system was comparable to the 7th edition, with no major improvements in survival discrimination. The recently implemented changes in N classification do not appear to improve the prognostic performance of the AJCC cancer staging system with regard to survival in GBC patients. ABSTRACT: The scope of our study was to compare the predictive ability of American Joint Committee on Cancer (AJCC) 7th and 8th edition in gallbladder carcinoma (GBC) patients, investigate the effect of AJCC 8th nodal status on the survival, and identify risk factors associated with the survival after N reclassification using the National Cancer Database (NCDB) in the period 2005–2015. The cohort consisted of 7743 patients diagnosed with GBC; 202 patients met the criteria for reclassification and were denoted as stage ≥III by AJCC 7th and 8th edition criteria. Overall survival concordance indices were similar for patients when classified by AJCC 8th (OS c-index: 0.665) versus AJCC 7th edition (OS c-index: 0.663). Relative mortality was higher within strata of T1, T2, and T3 patients with N2 compared with N1 stage (T1 HR: 2.258, p < 0.001; T2 HR: 1.607, p < 0.001; Τ3 HR: 1.306, p < 0.001). The risk of death was higher in T1–T3 patients with Nx compared with N1 stage (T1 HR: 1.281, p = 0.043, T2 HR: 2.221, p < 0.001, T3 HR: 2.194, p < 0.001). In patients with AJCC 8th edition stage ≥IIIB GBC and an available grade, univariate analysis showed that higher stage, Charlson–Deyo score ≥ 2, higher tumor grade, and unknown nodal status were associated with an increased risk of death, while year of diagnosis after 2013, academic center, chemotherapy. and radiation therapy were associated with decreased risk of death. Chemotherapy and radiation therapy were associated with decreased risk of death in patients with T3–T4 and T2–T4 GBC, respectively. In conclusion, the updated AJCC 8th GBC staging system was comparable to the 7th edition, with the recently implemented changes in N classification assessment failing to improve the prognostic performance of the staging system. Further prospective studies are needed to validate the T2 stage subclassification as well as to clarify the association, if any is actually present, between advanced N staging and increased risk of death in patients of the same T stage.