Age-Stratified Clinicopathological Features and Efficacy of Adjuvant Chemotherapy in Resectable Gastric Cancer: An East-West Population-Based Study

<b>Background:</b> The incidence of early-onset gastric cancer (EOGC) has been steadily increasing in recent years. However, the efficacy of adjuvant chemotherapy (AC) in this population remains unclear. This study aimed to investigate the clinicopathological characteristics, survival outcomes, and efficacy of AC between EOGC and average-onset gastric cancer (AOGC) patients. <b>Methods:</b> Patients with stage II-III gastric adenocarcinomas who underwent curative D2 gastrectomy at the Sixth Affiliated Hospital of Sun Yat-sen University from January 2014 to December 2021 were enrolled and classified into two groups: EOGC (≤45 years) and AOGC (>45 years) groups. Clinicopathological characteristics, overall survival (OS), and efficacy of AC were compared between the two groups. Western and East Asian cohorts were included as external validation sets to compare the efficacy of AC between different age groups. <b>Results:</b> Compared to AOGC, EOGC patients exhibited a higher proportion of females, poor differentiation, diffuse Lauren type, middle-third GC, perineural invasion (PNI), and receipt of AC. Univariate and multivariate analyses identified that T stage, N stage, PNI, and AC were independent prognostic factors for OS. After balancing the baseline characteristics between patients who received AC and those who did not, the Kaplan-Meier survival curves indicated that AC significantly improved OS across all patients. Further subgroup analysis revealed a survival benefit of AC in AOGC patients, whereas no significant survival difference was observed in the EOGC subgroup. Consistently, external validation in both Western and East Asian cohorts confirmed that AC did not confer a survival advantage in EOGC patients. <b>Conclusions:</b> EOGC exhibits aggressive pathological characteristics, and chemotherapy does not consistently improve survival in EOGC patients.