A Real-World Study of the Incidence and Outcomes of Early-Onset Well-differentiated Neuroendocrine Neoplasms

Objective: The objective of this study was to evaluate the incidence and outcomes of adults with early-onset (20 to 34 y) diagnosis of well-differentiated neuroendocrine neoplasms. Methods: Surveillance, Epidemiology, and End Results (SEER)-18 database was accessed, and patients with well-differentiated lung or digestive tract neuroendocrine neoplasms diagnosed 2000 to 2018 were reviewed. Annual percent changes (APCs) were calculated for the 3 disease subsites (foregut, midgut, and hindgut) stratified by age group. Kaplan-Meier survival estimates/log-rank testing were used to examine differences in overall survival between the 3 age groups. Multivariable Cox regression analyses were used to evaluate factors affecting overall and cancer-specific survivals. Results: Throughout the study period, patients with early-onset disease (20 to 34 y) have experienced the greatest APC (20 to 34 y: 9.7; 35 to 49 y: 5.4; >= 50 y: 4.1). When APCs were stratified by disease subsite, this difference in APCs appears to be driven by midgut tumors (20 to 34 y: 19.2; 35 to 49: 8.4; >= 50 y: 3.8). Using multivariable Cox regression modeling, the following variables were associated with a higher risk of all-cause death (worse overall survival): male sex (hazard ratio [HR] 1.27; 95% confidence interval [CI]: 1.22-1.31), African American race (HR vs. white race: 1.20; 95% CI: 1.15-1.26), nonhindgut primary (HR foregut vs. hindgut primary: 2.02; 95% CI: 1.91-2.13; HR midgut vs. hindgut primary: 2.09; 95% CI: 1.95-2.24), distant disease (HR vs. regional disease: 2.06; 95% CI: 1.96-2.18), no surgery to the primary (HR: 2.34; 95% CI: 2.24-2.46), and older age (HR: 5.80; 95% CI: 4.87-6.91). Conclusion: Cases of early-onset well-differentiated neuroendocrine neoplasms have disproportionately increased over the past 2 decades (compared with other age groups), and this appears to have been driven mainly by midgut tumors.