Timing and Clinical Significance of Chemotherapy in Patients with Resected Gastric Adenocarcinoma: A Population-based Cohort Study.

Background: This study was to assess the impact of chemotherapy sequence on the prognosis of patients with gastric cancer (GC) undergoing gastrectomy and identify optimal chemotherapy timing along with potential candidates.

Patients and methods: Data on patients who underwent gastrectomy was extracted from Surveillance, Epidemiology, and End Results database. Prognostic factors for overall survival (OS) were assessed using Kaplan-Meier and Cox regression analyses. Treatment strategies were categorized into neoadjuvant chemotherapy (NAC), adjuvant chemotherapy (AC), and perioperative chemotherapy (PC), with subsequent analyses of clinical outcomes. Stable inverse probability of treatment weighting (sIPTW) and subgroup analyses were conducted to evaluate significance of chemotherapy timing.

Results: Among 4914 patients, 38.4% received NAC, 45% received AC, and 16.6% received PC. The 5-year OS rates for the entire cohort were 41.2%. Although no significant differences were observed between NAC and AC, PC exhibited a substantial improvement in OS compared to both. Multivariate analysis highlighted chemotherapy timing as a prognostic factor for OS. Even after sIPTW, PC still demonstrated significantly longer OS compared to NAC and AC, and this trend persisted across almost all subgroups. Even after patients undergoing NAC and gastrectomy, AC remained essential. Notably, potential candidates exempt from AC were identified, including patients aged ≥65 years and those with tumor grades I-II.

Conclusions: Chemotherapy timing was independent prognostic factors for resected GC. PC presented as a promising strategy, displaying superior OS compared to both NAC and AC. However, older individuals and those with well-differentiated tumors could considered exempt from further AC after receiving NAC and gastrectomy. Further research is needed to validate these findings and optimize GC management.