Appendiceal adenocarcinoma diagnosed before age 50 years: temporal trends, histologic patterns, and survival outcomes, 2000-2023

Appendiceal adenocarcinoma is a 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 cohort. A retrospective study of data from the SEER database (17 registries, 2000-2023) identified 10,452 patients with appendiceal adenocarcinoma. Among these patients, 2219 (21.2%) were early-onset. The early-onset patients were more likely to be Hispanic (20% versus 12% of average-onset patients; p<0.001), to present with distant disease (52% versus 46%; p<0.001), and have mucinous histology (63% versus 56%; p<0.001). The proportion of early-onset cases declined from approximately 28% in 2000-2002 to 18% by 2023 (slope -0.36% per year; p<0.001). In multivariable analysis, average-onset was independently associated with higher hazard of overall death (HR 1.55; 95% CI 1.44-1.67) and cancer-specific death (1.26; 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). The authors conclude that early-onset appendiceal adenocarcinoma accounts for approximately one in five cases in the US 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.