Modified gastric cancer ypTNM staging based on optimized lymph node staging: A large-sample, international multicenter study.

[BACKGROUND] The prognostic accuracy of the AJCC 8th Edition ypTNM staging system for patients diagnosed with gastric cancer (GC) after neoadjuvant therapy (NAT) remains controversial.

[METHODS] Data from 1078 patients diagnosed with locally advanced GC, who underwent NAT at international multicenter institutions, were retrospectively analyzed. Optimal lymph node staging was determined based on overall survival (OS) and disease-specific survival (DSS), with the subsequent development of a novel ypTNM staging system. The prognostic performance of the AJCC 8th Edition ypTNM and modified staging systems were compared and validated using information obtained from databases in the United States.

[RESULTS] The optimal ypN cut-offs were 0, 1, and 8 nodes for ypN0-ypN3, respectively. The modified ypN category demonstrated superior prognostic discrimination between each adjacent stage, with significant differences in three-year OS (p=0.034, <0.001, <0.001) and DSS (p=0.015, 0.009, <0.001). Two-step multivariate Cox regression confirmed the enhanced predictive performance of the modified lymph node staging system. The new ypTNM system stratified patients into 6 subgroups (ypCR, I-IIIB), demonstrating improved accuracy (C-index, OS 0.694 versus [vs.] 0.647; DSS, 0.696 vs. 0.650; both p<0.001), model fit (lower Akaike information criterion/Bayesian information criterion), clinical utility (Net reclassification index, 38.62%/37.80%; integrated discrimination improvement, 7.60%/7.20%), and stability (time-dependent receiver operating characteristic curve). External validation (n = 1637) confirmed its superiority (all p<0.05).

[CONCLUSION] This internationally validated modified ypTNM system, based on optimized lymph node staging, outperformed the AJCC 8th Edition in terms of prognostic accuracy for patients diagnosed with GC post-NAT, offering a more precise tool for clinical decision making.