Early‐Onset Gastric Cancer as a High‐Risk Disease Entity in the United States: Clinicopathologic Features, Regional Variation, and Outcomes

INTRODUCTION: Early-onset gastric cancer (EOGC), defined as diagnosis before age 45, represents a distinct and increasingly recognized subset of gastric cancer. Emerging evidence suggests that clinical behavior, treatment patterns, and outcomes differ from average-onset disease, yet these differences remain incompletely characterized. We evaluated demographic, geographic, pathologic, treatment, and survival patterns in patients with EOGC. METHODS: This retrospective cohort study included patients with stage II-III gastric cancer diagnosed between 2006 and 2022 who underwent curative-intent gastrectomy in the National Cancer Database (NCDB). EOGC was defined as age ≤ 45 years at diagnosis. Demographic, pathologic, and treatment variables were analyzed. Overall survival (OS) was estimated using Kaplan-Meier methods and Cox proportional hazards models. A landmark analysis excluding patients with < 6 months of follow-up addressed survivorship bias. RESULTS: Across nearly two decades, EOGC accounted for 7.3% of the cohort and demonstrated demographic and geographic concentration, particularly among Hispanic, Black, and Asian patients. EOGC was associated with aggressive clinicopathologic features, including diffuse or signet-ring histology, poor differentiation, and advanced nodal disease. Although patients with EOGC more frequently received perioperative or neoadjuvant chemotherapy compared with older cohorts, pathologic complete response rates remained low, underscoring limited benefit from treatment intensification alone. CONCLUSIONS: Despite receipt of more intensive multimodality therapy, EOGC did not demonstrate superior survival outcomes. These findings highlight EOGC as a clinically distinct, high-risk disease subtype and support the need for biomarker-driven therapeutic strategies and earlier detection efforts in high-risk populations.