Prognosis and distant metastasis patterns of early-onset gastric cancer compared with late-onset: a large-scale, cross-population retrospective study.

[BACKGROUND] Early-onset gastric cancer (EOGC) (≤45 years) exhibits distinct clinicopathological characteristics, and its incidence is rising. This study aimed to provide comprehensive insights into age-related differences in gastric cancer by retrospectively analyzing the clinicopathological characteristics, survival outcomes, recurrence dynamics, and distant metastasis patterns of EOGC compared with late-onset gastric cancer (LOGC).

[METHODS] We performed a retrospective analysis of data from 33 675 patients with gastric cancer in the Surveillance, Epidemiology, and End Results (SEER) database and Zhejiang Cancer Hospital, including 3208 patients with EOGC and 30 467 patients with LOGC. Restricted cubic spline analysis (RCS) was used to evaluate the nonlinear relationship between age and mortality risk. Propensity score matching (PSM) was used to balance baseline differences between groups. Survival outcomes-including overall survival (OS), cancer-specific survival (CSS), and disease-free survival (DFS)-were evaluated using Kaplan-Meier analysis, log-rank tests, and Cox proportional hazards models. Subgroup analyses were conducted to further explore prognostic heterogeneity.

[RESULT] Despite patients with EOGC presenting with unfavorable clinicopathological features, analyses of OS, CSS, DFS, and recurrence-related indicators consistently showed that EOGC is associated with a robust survival advantage across populations. As a representative finding, after PSM, the 5-year OS was 48.3% vs 43.1% in SEER (HR=0.83; P <.001) and 72.6% vs 64.3% in the Chinese cohort (HR=0.71; P <.001). Subgroup analysis further indicated that patients with EOGC exhibited a significant survival advantage with smaller tumor size, signet ring cell carcinoma subtype, and stages I to III (P for interaction <.05). In addition, the distant metastasis pattern in patients with EOGC differed from patients with LOGC, with patients with EOGC more frequently developing bone and ovarian metastases, whereas liver metastasis was less common. Patients with EOGC with peritoneal metastasis had poorer outcomes than patients with LOGC. In patients with EOGC, among different metastatic sites, those with distant lymph node metastasis have a relatively better prognosis, whereas patients with peritoneal metastasis have a less optimistic prognosis (HR=2.23; P =.031).

[CONCLUSION] Patients with surgically treated EOGC have significantly better prognoses than patients with LOGC. Furthermore, the distant metastasis patterns of EOGC differ from LOGC, carrying distinct prognostic implications for different metastatic sites.