A novel ypN-TRG staging system for gastric cancer patients after neoadjuvant therapy based on the metro-ticket paradigm: a multicenter and large sample retrospective analysis.

Abstract

Background: Conventional ypT category evaluates the depth of invasion after neoadjuvant therapy (NAT) for gastric cancer (GC) and has limited prognostic value. Tumor regression grade (TRG) measures the extent of tumor response to treatment, and when combined with the ypN category, it may enhance the prediction of patient outcomes. This study aims to develop a new staging system by integrating TRG and ypN category to better evaluate the prognosis of GC patients receiving NAT.

Methods: This retrospective analysis included 962 patients who underwent radical gastrectomy after NAT, with 513 in the development cohort (from one center) and 449 in the external validation cohort (from five centers). The ypN-TRG staging system was established by calculating the distance from the origin on a cartesian plane incorporating the ypN (x-axis) stage and TRG (y-axis) grade, and five sub-stages were delineated.

Results: In the development cohort, 3-year overall survival rates according to ypN-TRG stage I, IIA, IIB, IIIA, IIB were 87.6%, 80.2%, 70.7%, 47.3%, 21.5%, p < 0.01. Compared with ypTNM, the ypN-TRG staging system performed better in terms of the prognostic discrimination power (C-index), goodness-of-fit (AIC, BIC), model improvement (NRI, IDI), and model stability (time-AUC). Multivariate Cox regression analysis confirmed the superiority of ypN-TRG over ypTNM staging. In the external validation cohort, ypN-TRG staging was a better predictor of OS and DFS in patients with GC.

Conclusions: The ypN-TRG staging system is superior to the AJCC eighth edition ypTNM staging system in accurately assessing the prognosis of patients with GC after NAT.