Survival Outcomes in Early Onset Appendiceal Adenocarcinoma (EOAA)

The incidence of early onset (age < 50 years at diagnosis) appendiceal adenocarcinoma (EOAA) is rising alarmingly. Reported data on etiology, treatment, and outcomes is scarce. In this study, we report clinical outcomes for patients with EOAA.

Patients diagnosed with appendiceal adenocarcinoma between 2013 and 24 were stratified on the basis of age at diagnosis as having either EOAA (< 50 years) or average-age onset appendiceal adenocarcinoma (AOAA; ≥ 50 years). Clinicopathological and genomic data were abstracted from electronic medical records. Baseline clinicopathologic features and survival outcomes were compared between patients with EOAA and AOAA.

Of 181 eligible patients, 49 (27.1%) had EOAA. Median age at diagnosis for patients with EOAA was 42.1 years (interquartile range [IQR], 35.7-46). Of the 76 patients (EOAA = 23 [30.3%] + AOAA = 53 (69.7%)] who had locoregional disease at presentation, 44 (57.9%) remained disease-free for at least 2 years. Within these 44 (conditional survival), the EOAA group showed numerically shorter recurrence-free survival (RFS) and higher risk of recurrence (median RFS, EOAA = 49.5 months versus AOAA = 83.3 months; hazard ratio [HR], 4.07; 95% confidence interval [CI], 1.49-11.18; p = 0.06). Long-term recurrences (≥ 5 years) were seen in 9/15 (60%) patients during the 5-year follow-up period. Of 139 evaluable patients (EOAA = 36 [25.9%] + AOAA = 103 [74.1%]) with metastatic/recurrent disease, patients with EOAA received more non-fluorouracil (FU)-based systemic treatments, including experimental agents, in any line of treatment (8/36, 22.2% versus 6/103, 5.8%; p = 0.009). A higher proportion of patients in the EOAA group received bevacizumab in any line of treatment (24/36, 66.7% versus 49/103, 47.6%; p = 0.055) and three or more lines of systemic therapy (10/36, 27.8% versus 14/103, 13.6%; p = 0.07). There was no significant difference in OS between the EOAA and AOAA groups despite more aggressive therapy in EOAA (median OS, EOAA = 35.2 months versus AOAA = 40.6 months; HR, 0.90; 95% CI, 0.57-1.44; p = 0.66).

Among patients who remained disease-free after initial surgical resection for locoregional disease for at least 2 years, recurrence was more frequent in patients with EOAA. Aggressive systemic therapy, including trials and non-FU based therapies were more frequent in patients with EOAA but were not associated with improved survival. EOAA may represent a unique entity within this rare disease, which warrants further exploration.