Appraisal of Residual Tumor Burden on Survival Prognosis Following Neoadjuvant Chemotherapy in Locally Advanced Gastric Cancer: A Multicenter Cohort Study.

Background: The eighth edition American Joint Committee on Cancer (AJCC) guidelines introduced the postneoadjuvant therapy pathologic tumor, node, metastasis (ypTNM) staging system to assess gastric cancer prognosis postneoadjuvant chemotherapy; however, it overlooks other residual tumor burden aspects beyond tumor infiltration depth and positive lymph nodes.

Methods: Data from 537 locally advanced gastric cancer patients (cT2-4NanyM0) treated with neoadjuvant chemotherapy (2010-2021) across six tertiary centers were analyzed. Prognostic factors for overall survival (OS) and recurrence-free survival (RFS) were identified using Cox regression. Reduction of carcinoembryonic antigen (ΔCEA), Response Evaluation Criteria in Solid Tumors (RECIST) criteria, and pathologic nodal stage after neoadjuvant therapy (ypN) were incorporated into a nomogram, validated by receiver operating characteristic (ROC), C-index, calibration plots, and decision curve analyses. A novel prognostic staging system was developed on the basis of the interquartile range (IQR) of the nomogram scores.

Results: The study included a training cohort of 320 patients and a validation cohort of 217. In the training cohort, multivariate Cox regression identified ypN, RECIST criteria, and ΔCEA as independent prognostic factors for OS and RFS. Nomograms for OS and RFS were developed, showing superior prognostic ability against the American Joint Committee on Cancer (AJCC) eighth edition ypTNM staging for OS (C-index: 0.792 versus 0.689; AIC: 731.268 versus 782.089; BIC: 733.737 versus 784.459) and RFS (C-index: 0.763 versus 0.679; AIC: 868.146 versus 906.772; BIC: 893.301 versus 915.299). The new system improved 3-year OS (89.7%, 64.2%, 60.2%, and 23.0%, p < 0.001) and RFS (84.3%, 79.0%, 65.1%, and 30.0%, p < 0.001) stratification over AJCC stages. Similar results were observed in the validation cohort.

Conclusions: The novel staging system, based on residual tumor burden, significantly outperforms ypTNM staging, enhancing prognostic prediction accuracy in postneoadjuvant chemotherapy patients with gastric cancer.