Abstract Background: The incidence of metastatic gastric cancer among young adults is rising and has a dismal prognosis with 5-year survival of only 4%. Little is known about the clinicopathologic features associated with metastatic vs locoregional disease in young adults compared to older adults. Methods: This retrospective case control study evaluated patients treated for gastric cancer at USC Norris Comprehensive Cancer Center and LA General Hospital from 2000-2022. Sociodemographic characteristics, clinical presentation and tumor features were compared for early-onset (EO; age 50 years) cases and typical onset (TO; 50 years) controls in a 1: 2 ratio matched by diagnosis year and facility. All analyses were performed within matched sets, with three samples per set. Using conditional logistic regression to estimate odds ratios, the pooled analysis tested whether there is an association between sociodemographic, clinical and tumor characteristics and metastatic vs locoregional presentation in aggregate. The early versus older onset analysis examined whether these associations differ by onset type, in terms of either the direction or the magnitude of the association. Results: 795 patients were evaluable (265 EO, 530 TO). Hispanic patients are more likely to present with metastatic disease compared to Asian (OR=2. 22, 95%CI 1. 34-3. 70, p=0. 002). Non-Hispanic White are more likely to present with metastatic disease compared to Asian (OR=2. 97, 95%CI 1. 61-55. 48, p0. 001). This association did not differ by EO vs TO. There was no difference in stage at presentation by sex, BMI, primary location of tumor or H. pylori status of the tumor. Overall, patients with intestinal histologic compared to diffuse histologic characteristics are less likely to present with metastatic disease (OR=0. 30, 95%CI 0. 11-0. 85, p=0. 023). This association does not differ between EO and TO (p=0. 48). There was no difference in the association between MSI status and metastatic disease by EO vs TO (p=0. 54). Patients with HER2 amplified status are more likely to present with metastatic disease compared to patients with non-amplified HER2 (OR=2. 97, 95%CI 1. 25-7. 09, p=0. 014) ; however, there was no difference in risk between EO vs TO (p=0. 87). Patients with a negative endoscopy prior to diagnosis (16% EO, 18% TO) were equally likely to present with locoregional or metastatic disease (p=0. 91). There was no difference in association between metastatic disease and smoking or alcohol use (p=0. 069, p=0. 64 respectively). Conclusions: Early detection of gastric cancer, especially in non-Asian communities, is crucial as they are more likely to present with metastatic disease. The similarities in disease presentation and characteristics between early vs older onset patients suggests unmeasured environmental exposures may be associated with adverse biological features driving the rising incidence of metastatic disease in young adults. Deeper molecular characterization of metastatic vs locoregional patients may identify other factors contributing to poor outcomes. Citation Format: Jessica Sheth Bhutada, Fox Bravo, Maureen Cairns, Qi Nie4, Ruopei Wu, Danielle Estell, Arthur Bookstein, Justine Po, Myles Cockburn, Chanita Hughes Halbert, Syma Iqbal, David Freyer. Clinicopathologic features associated with metastatic early-onset gastric cancer abstract. In: Proceedings of the AACR Special Conference in Cancer Research: The Rise in Early-Onset Cancers—Knowledge Gaps and Research Opportunities; 2025 Dec 10-13; Montreal, QC, Canada. Philadelphia (PA): AACR; Clin Cancer Res 2025;31 (23Suppl): Abstract nr B031.
Bhutada et al. (2025) studied this question.