Early-onset appendiceal cancer (EOAC), diagnosed before age 50, accounts for approximately 30% of all appendiceal malignancies. Its clinical profile, treatment strategies, and outcomes remain underexplored compared to late-onset disease. This study aimed to assess demographics, disease profile, management, and outcomes of EOAC.

A retrospective cohort study using NCDB data (2005–2019), including patients with stage-known appendiceal adenocarcinomas or neuroendocrine tumors (NETs), was condcuted. Patients were categorized as EOAC (< 50 years) or late-onset appendiceal cancer (LOAC). Demographics, tumor features, treatments, and outcomes were compared. Kaplan-Meier and Cox proportional hazard analyses were used to assess overall survival (OS) and predictors of mortality. The primary outcome was 5-year OS.

Among 27,276 patients (55.9% females, median age: 58 years), 30.6% had EOAC. EOAC patients were more often female, Hispanic, and privately insured. Most EOACs were NETs, low-grade, and early-stage (stage I: 39.4% vs. 21.2%; p < 0.001). EOAC was treated more often with appendectomy and minimally invasive surgery, less often with hemicolectomy or chemotherapy. EOAC had better 5-year OS than LOAC (79.9% vs. 59.3%, p < 0.001), consistent across all histologic types and stages. EOAC patients had shorter hospital stays and significantly lower rates of positive surgical margins, 30- and 90-day mortality, and unplanned readmission.

EOAC was associated with significantly higher OS than LOAC, across all disease stages and tumor histologies. This finding should be interpreted in light of disparities in patient and disease characteristics and treatments between the two groups, as EOACs were generally smaller, early stage and low grade, and consisted mainly of NETs compared to LOAC.