Optimizing Surgical Timing Following Neoadjuvant Therapy for Gastric Cancer: Insights from a Multicenter Retrospective Analysis

Neoadjuvant therapy (NAT) is a cornerstone in the treatment of locally advanced gastric cancer, improving surgical outcomes and survival. However, the optimal timing for surgery following NAT remains controversial. This study evaluates the impact of the interval between NAT and surgery on overall survival (OS) and explores associated clinicopathological factors. A retrospective analysis of 893 patients undergoing NAT and curative surgery for gastric adenocarcinoma across three centers in China was conducted. Surgical intervals were categorized (∼28 days, 29-42 days, >42 days). Survival analyses employed restricted cubic spline (RCS) models, Kaplan-Meier methods, and Cox proportional hazards regression. Patients operated on within 28 days post-NAT had the most favorable OS, while intervals longer than 28 days were independently associated with worse outcomes. RCS analysis revealed increased risks for intervals longer than 28 days. Prolonged intervals showed declining effectiveness in tumor regression. Stratified analyses indicated that patients with poor NAT response (TRG 3) particularly benefited from surgery within 4 weeks, while delays were detrimental. Timely surgery, especially within 4 weeks post-NAT, optimizes survival outcomes, particularly in patients with limited NAT response. This study underscores the need for individualized surgical timing and calls for prospective multicenter validation.