A novel TRG-ypT-ypN 3D staging system for locally advanced gastric cancer patients after neoadjuvant therapy: a multicenter real-world study

The 8th edition AJCC ypTNM system does not consider tumor regression after neoadjuvant therapy (NAT), which may limit the prognostic accuracy in locally advanced gastric cancer (LAGC). This multicenter real-world study included 1270 patients who underwent radical gastrectomy after NAT between January 2020 and January 2025 across twelve institutions, including 763 treated with neoadjuvant immunochemotherapy (NICT) and 507 treated with neoadjuvant chemotherapy (NCT). The cohort was divided by institution into a training cohort ( n = 843) and a validation cohort ( n = 427). A TRG-ypT-ypN three-dimensional (3D) staging system was developed in the training cohort using a Cartesian coordinate framework and evaluated in the validation cohort. In the overall NAT cohort, the 3-year overall survival rates for 3D stages I, II, IIIA, and IIIB were 91.9%, 78.1%, 54.9%, and 45.8%, respectively. The 3D staging system showed better prognostic performance than ypTNM in the training and validation cohorts, particularly in the NICT subgroup, whereas the NCT subgroup showed only a non-significant improvement trend. For relapse-free survival, the 3D system also demonstrated modestly improved prognostic performance. Overall, the TRG-ypT-ypN 3D staging system may complement ypTNM for postoperative prognostic assessment in LAGC patients undergoing NAT, especially in the NICT subgroup.