Evaluation of pathologic response and surgical safety of total neoadjuvant therapy for patients with clinical stage III gastric cancer in a real-world setting

Abstract

BackgroundPerioperative chemotherapy is the standard treatment for locally advanced gastric cancer. However, the potential benefit of extending therapy before surgery remains largely unknown. In this study, we aimed to evaluate the efficacy and safety of total neoadjuvant chemotherapy, with or without immune checkpoint blockade. MethodsA cohort of 174 patients with clinical stage III gastric cancer who underwent D2 gastrectomy from October 2021 to March 2024 in the real-world setting were included in this study. Among these patients, 101 were treated with total neoadjuvant therapy (TNT) and 73 were treated with perioperative neoadjuvant therapy (PNT). We compared the pathologic complete response (pCR) rate, ypN0 rate, recurrence-free survival (RFS), overall survival (OS), and postoperative complications between the 2 groups. Multivariate logistic regression analysis was conducted to identify factors associated with pCR or ypN0. ResultsCompared with the PNT group, the patients in the TNT group were more frequently treated with intensive chemotherapy with triplets + immunotherapy. Apart from this, there were no significant differences in baseline characteristics. There were no statistically significant differences in pCR (16.8% vs 12.3%), ypN0 (49.5% vs 38.4%), RFS, OS, and postoperative complications (27.7% vs 26.0%) between the TNT and PNT groups. Older age, diffuse type, and stable disease/progressive disease based on clinical efficacy evaluation were independently associated with non-pCR. Stable disease/progressive disease, linitis plastica, and poor differentiation were independently associated with ypN+. Neither the number of neoadjuvant therapy cycles nor the specific regimens were associated with pCR or ypN0. In the subgroup analysis of patients receiving total gastrectomy, there were still no statistically significant differences in pCR (16.7% vs 2.6%), ypN0 (43.8% vs 39.5%), and postoperative complications (45.8% vs 36.8%) between the 2 groups. ConclusionAlthough TNT did not increase the postoperative complication rate, it also did not provide any additional short-term benefits compared with PNT for clinical stage III gastric cancer.