The early-onset paradox of gastric cancer: Assessment of geographic clustering, biology, treatment, and outcomes.

4088 Background: Early-onset gastric cancer (EOGC), defined as diagnosis before age 45, represents an increasingly recognized and clinically distinct subset of gastric cancer (GC) in the United States. While prior studies largely from Asian cohorts suggest more aggressive tumor biology, contemporary U.S. data characterizing demographic patterns, treatment strategies, geographic variation, and outcomes in resectable disease is limited. Methods: Using a U.S. cancer registry (2006–2022), we studied patients aged 18–90 with stage II–III gastric cancer post-gastrectomy. Excluding palliative or incomplete cases, we analyzed overall survival (OS) via Cox models, adjusting for demographics and treatment. P-values were calculated using the Chi-square test to compare racial distribution across age groups. Results: Among eligible patients, 1,943 (7.4%) had EOGC. EOGC disproportionately affected Hispanic (23.8%; p < 0.001), Black (14.2%; p < 0.001), and Asian (10.2%; p < 0.001) populations, with White patients accounting for 49.4%, with a male predominance (2:1). Demographic and socioeconomic profiles were distinct within the EOGC population. A greater proportion of EOGC patients resided in areas with a median household income < $38,000 (17.1%; p = 0.025). The ≤45 group was more frequently uninsured (7.6%) or Medicaid insured (19.7%) and represented the highest proportion of residents from areas with the lowest educational attainment (21.6%). Geographic clusters emerged in the South/Middle Atlantic and Pacific (TX, CA, AK, HI). EOGC tumors more frequently exhibited diffuse or signet-ring histology (~30%) and advanced nodal involvement. Despite receiving more intensive multimodality therapy, including perioperative or neoadjuvant chemotherapy (74.1%), EOGC patients had lower pathologic response rates and no survival advantage. Median OS was 49.8 months (36-month OS: 58.3%). Conclusions: Even with aggressive treatment, EOGC shows worse pathology and no better survival rates than older-onset cases. New U.S. data confirms this aggressive biology and highlights significant demographic and socioeconomic disparities. To improve outcomes, the focus should shift from just intensifying treatment to prioritizing earlier detection and targeted regional screening. Demographic characteristics stratified by age groups. Variable ≤45 Years (n=1943) 46–69 Years (n=15927) ≥70 Years (n=8397) Total Cohort (N=26267) p-value Race, n (%) <0.001 White 960 (49.4) 10912 (68.5) 5918 (70.5) 17790 (67.7) Black 276 (14.2) 1890 (11.9) 838 (10.0) 3004 (11.4) Hispanic 462 (23.8) 1611 (10.1) 766 (9.1) 2839 (10.8) Asian 198 (10.2) 1166 (7.3) 731 (8.7) 2095 (8.0) Other 47 (2.4) 348 (2.2) 144 (1.7) 539 (2.1)