Epidemiology of Neuroendocrine Neoplasms in the US

Importance Neuroendocrine neoplasms (NENs) are increasing in incidence; prevalence and at the same time, practice patterns have also evolved, impacting classification and survival of these malignant neoplasms. However, updated epidemiological data are lacking. Objective To define the epidemiological and survival trends of patients with NENs in the US. Design, Setting, and Participants This cross-sectional study used data from the National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) program on NEN cases from 1975 to 2021. Analysis of project data was conducted between August 2023 and August 2024. Main Outcomes and Measures Annual age-adjusted incidence between 1975 and 2021, limited duration prevalence, and overall survival (OS) rates. Recent trends in survival were evaluated from 2000 to 2021 for the entire cohort as well as specific subgroups including distant stage gastrointestinal neuroendocrine tumors (NETs) and pancreatic NETs. Results In this analysis of 145 447 NEN cases (mean [SD] age, 61.4 [14.7] years; 76 057 female [52.4%]), the age-adjusted incidence rate increased 5.2-fold from 1975 (1.64 per 100 000 persons; 95% CI, 1.43-1.87 per 100 000 persons) to 2021 (8.52 per 100 000 persons; 95% CI, 8.33-8.70 per 100 000 persons) except for a dip in 2020 likely related to the COVID pandemic. This increase occurred across all sites, stages, and grades but was most marked for localized stage neoplasms (13-fold; 1975: 0.40 per 100 000 persons [95% CI, 0.30-0.52]; 2021: 5.04 per 100 000 persons [95% CI, 4.78-5.30]), well-differentiated neoplasms (53-fold; 1975: 0.04 per 100 000 persons [95% CI, 0.02-0.09]; 2021: 2.30 per 100 000 persons [95% CI, 2.13-2.48]), and neoplasms with the appendix (12-fold; 1975: 0.11 per 100 000 persons [95% CI, 0.09-0.22]; 2021: 1.68 per 100 000 persons [95% CI, 1.39-1.78]) or rectum (12-fold; 1975: 0.11 per 100 000 persons [95% CI, 0.06-0.18]; 2021: 1.32 per 100 000 persons [95% CI, 1.19-1.46]) as primary sites. Since 2000 (SEER 17 registry), the sites with the highest incidence rates included lung (1.49 per 100 000 persons) and gastroenteropancreatic (GEP) NENs (6.1 per 100 000 persons); within GEP NENs, small bowel (1.4 per 100 000 persons) and pancreas (1.3 per 100 000 persons) were the most common sites. The estimated 20-year limited duration prevalence of NENs in the US on January 1, 2021, was 248 546 cases. OS for all NENs improved from the 2000-2006 period to the 2014-2021 period (hazard ratio [HR], 1.42; 95% CI, 1.38-1.45). In addition, other factors associated with survival included age, stage, grade, and primary site of origin. The median OS for all NENs was 11.8 years, and for distant-stage, well-differentiated neuroendocrine tumors it was 6.7 years with 10-year OS ranging from 17 410 patients (15.4%) with rectum as primary site to 17 505 patients (51.7%) with small bowel as primary site. Conclusions and Relevance Incidence and prevalence of NENs continue to rise driven by increased diagnosis of early stage disease. Survival for NENs has also improved over time.