Abstract
BACKGROUND: Despite emerging evidence from studies on other malignancies that support early adjuvant chemotherapy (AC) initiation, the feasibility and oncologic benefits of this therapy remain underexplored in patients receiving gastric resection. AIM: To evaluate the feasibility, safety, and oncologic outcomes of early postoperative AC in advanced gastric cancer patients. METHODS: In this retrospective cohort study, 219 stage II/III gastric adenocarcinoma patients who underwent laparoscopic gastrectomy between 2016 and 2021 were analyzed. Patients were stratified by AC initiation timing: Early (10-13 days, n = 21) vs conventional (4-6 weeks, n = 198). Propensity score matching (1:2) was performed, with balance assessed via standardized mean differences. Recurrence-free survival, overall survival, and safety were compared between the two groups. Sensitivity analyses were conducted to assess the robustness of the findings. RESULTS: After 1:2 matching (21 patients vs 42 patients), early AC demonstrated comparable 3-year recurrence-free survival (53.7% vs 61.6%, hazard ratio = 0.89, P = 0.562) and overall survival (69.1% vs 66.3%, P = 0.874) rates to conventional timing. Peritoneal recurrence was significantly lower in the early group (4.8% vs 26.2%, P = 0.048), although Cox regression did not confirm a significant difference (hazard ratio = 0.418, P = 0.257). Early initiation correlated with a 2.18-fold greater proportion of patients requiring dose reductions (57.1% vs 26.2%, P = 0.026) but similar grade 3/4 toxicity (42.9% vs 57.1%, P = 0.285). CONCLUSION: Early AC initiation appears feasible in selected patients but necessitates individualized dose management. Our findings challenge traditional timing paradigms while highlighting the need for molecularly guided treatment sequencing strategies.