Development of a staging system for hepatoid adenocarcinoma of the stomach based on multicenter data: A retrospective cohort study: A Staging System for Hepatoid Adenocarcinoma of the Stomach.

Background: Hepatoid adenocarcinoma of the stomach (HAS) is a rare subtype of gastric cancer (GC) with a poor prognosis. Furthermore, the current pathological staging system for HAS does not distinguish it from that for common gastric cancer (CGC).

Methods: The clinicopathological data of 251 patients with primary HAS who underwent radical surgery at 14 centers in China from April 2004 to December 2019 and 5082 patients with primary CGC who underwent radical surgery at 2 centers during the same period were retrospectively analyzed. A modified staging system was established based on the differences in survival.

Results: After 1:4 propensity score matching (PSM), 228 patients with HAS and 828 patients with CGC were analyzed. Kaplan-Meier (K-M) analysis showed patients with HAS had a poorer prognosis compared with CGC. Multivariate analysis identified pN stage, CEA level, and perineural invasion (PNI) as independent prognostic factors in patients with HAS. A modified pT (mpT) staging was derived using recursive partitioning analysis (RPA) incorporating PNI and pT staging. The modified pathological staging system (mpTNM) integrated the mpT and the 8th American Joint Committee on Cancer (AJCC) pN definitions. Multivariate analysis showed that mpTNM stage outperformed other pathological variables as independent predictors of OS and RFS in patients with HAS. The mpTNM staging system exhibited significantly higher predictive accuracy for 3-year OS in patients with HAS (0.707, 95% CI: 0.650-0.763) compared to that of the 8th AJCC staging system (0.667, 95% CI: 0.610-0.723, P<0.05). Analysis using the Akaike information criterion favored the mpTNM staging system over the 8th AJCC staging system (824.69 vs. 835.94) regarding the goodness of fit. The mpTNM stages showed improved homogeneity in survival prediction (likelihood ratio: 41.51 vs. 27.10). Comparatively the mpTNM staging system outperformed the 8th AJCC staging system in survival prediction, supported by improvements in the net reclassification index (NRI: 47.7%) and integrated discrimination improvement (IDI: 0.083, P<0.05). Time-dependent ROC curve showed that the mpTNM staging system consistently outperformed the 8th AJCC staging system with increasing observation time.

Conclusion: The mpTNM staging system exhibited superior postoperative prognostic accuracy for patients with HAS compared to the 8th AJCC staging system.