Timing of Adjuvant Chemotherapy After Gastrectomy in Patients With Stage II to III Gastric Cancer: A Target Trial...

Uncertainty persists regarding the optimal interval between D2 gastrectomy and initiation of adjuvant chemotherapy (AC) for stage II to III gastric cancer (GC). We investigated whether delaying treatment beyond 6 weeks compromises overall survival.

Using multicenter observational data (2010-2022), we emulated a pragmatic noninferiority target trial to compare AC initiation at ≤6 versus 7-12 weeks postgastrectomy. Eligible patients had received curative-intent surgery for stage II to III GC. The AC regimen comprised platinum-based agents plus fluoropyrimidines. The primary end point was 5-year all-cause mortality from surgery to death or administrative censoring (30 June 2025). The Clone-censor-weighting approach was used, and inverse probability weighting achieved balance across baseline and postoperative time-varying covariates (standardized mean difference <0.1). Weighted pooled logistic regression estimated cumulative mortality; risk differences (RDs) and risk ratios (RRs) were computed from 500 bootstrap samples. The prespecified noninferiority margin was an absolute 10% increase in 5-year mortality.

Among 1,637 eligible patients, 35.9% initiated AC within 6 weeks (median 37 days), whereas 17.5% began between 7 and 12 weeks postoperatively. Delayed initiation (7-12 weeks) met the noninferiority criterion: the absolute RD in 5-year mortality was -0.52% (95% CI, -7.95 to 7.41), with the upper confidence limit below the 10% margin. The noninferiority finding was robust to weight trimming and to alternative imputation strategies. No significant difference in mortality was observed across clinically relevant subgroups.

Initiating AC 7-12 weeks after D2 gastrectomy appeared to be noninferior to initiation within 6 weeks with respect to 5-year mortality in stage II to III GC; however, residual confounding cannot be excluded and the findings require validation in further studies.