Early-Onset Appendiceal Adenocarcinoma (Age < 50 Years): Temporal Trends in Case Proportions, Histologic Patterns, and Survival Outcomes From SEER, 2000-2023.

BACKGROUND: Appendiceal adenocarcinoma is a rare gastrointestinal malignancy with rising incidence. The clinicopathologic features and outcomes of patients with a diagnosis before age 50 years (early-onset disease) have not been characterized in a large-scale contemporary national cohort. METHODS: The study identified 10,452 patients with appendiceal adenocarcinoma from the SEER Research Data, 17 Registries, 2000-2023. Patients were classified as early-onset (age < 50 years) or average-onset (age ≥ 50 years). Kaplan-Meier and multivariable Cox regression analyses were performed for overall survival (OS) and cancer-specific survival (CSS). RESULTS: Among the 10,452 patients, 2219 (21.2%) were early-onset. The early-onset patients were more likely to be Hispanic (20% vs. 12%), to present with distant disease (52% vs. 46%), and to have mucinous histology (63% vs. 56%) (all p < 0.001). The proportion of early-onset cases declined from approximately 28% in 2000-2002 to 18% by 2022-2023 (slope-0.36% per year; p < 0.001). In multivariable analysis, average-onset age was independently associated with higher hazard of overall death (hazard ratio [HR] 1.55; 95% confidence interval [CI] 1.44-1.67) and cancer-specific death (HR 1.26; 95% CI 1.16-1.36). Non-Hispanic black patients had independently worse survival in both the full cohort (HR 1.16) and the early-onset subgroup (HR 1.35). CONCLUSIONS: Early-onset appendiceal adenocarcinoma accounts for approximately one in five cases nationally and carries distinct demographic and histologic features. After adjustment, survival was shown to be driven primarily by stage and tumor characteristics rather than by age alone. Racial survival disparities in the early-onset population warrant further investigation.