Abstract
BACKGROUND: A thorough investigation into the clinicopathologic features and long-term prognosis of early-onset gastroenteropancreatic neuroendocrine tumors (GEP-NETs) is lacking. This study leverages the Surveillance, Epidemiology, and End Results (SEER) database to comprehensively analyze these aspects, addressing this critical knowledge gap. METHODS: Patients diagnosed with GEP-NETs between 2010 and 2020 were categorized into early-onset (≤ 50 years) and late-onset (> 50 years) groups. Clinicopathological features were compared, and propensity score matching (PSM) was applied to mitigate confounding. Kaplan-Meier curves and Cox regression analysis were utilized to evaluate overall survival (OS) and cancer-specific survival (CSS). RESULTS: Among 35,342 patients (9,968 early-onset; 25,374 late-onset), both groups exhibited rising annual incidence. Early-onset GEP-NETs were more frequently located in the colorectum (66.8% vs. 40.0%) and had higher surgical rates (86.1% vs. 76.1%). They demonstrated superior OS and CSS compared to late-onset counterparts (P < 0.001), confirmed by 1:1 PSM. Lymph node metastasis was lower in early-onset GEP-NETs overall (11.9% vs. 19.7%), but paradoxically higher in small intestine subsets (53.1% vs. 46.9%). Distant metastasis rates were lower in early-onset tumors (5.5% vs. 9.9%), particularly in colorectum (1.2% vs. 3.2%). Predictors of lymph node metastasis in early-onset cases included race, marital status, tumor grade, primary site, T stage, and M stage; predictors of distant metastasis encompassed tumor grade, primary site, T stage, and N stage. Five-year OS and CSS rates for early-onset GEP-NETs were 95.0% and 97.4%, respectively. Multivariate analysis identified marital status, tumor grade, primary site, NM stage, surgery, and chemotherapy as independent OS predictors; tumor grade, primary site, NM stage, surgery, and chemotherapy independently predicted CSS. CONCLUSIONS: Early-onset GEP-NETs exhibit favorable survival and reduced metastasis rates relative to late-onset tumors, underscoring distinct clinical outcomes and warranting tailored management strategies.