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. 2025 Jun 2;8(6):e2515798.
doi: 10.1001/jamanetworkopen.2025.15798.

Epidemiology of Neuroendocrine Neoplasms in the US

Arvind Dasari  1 , Katrine Wallace  2 , Daniel M Halperin  3 , Jessica Maxwell  4 , Pamela Kunz  5 , Simron Singh  6   7 , Beth Chasen  8 , James C Yao  1
Affiliations

Epidemiology of Neuroendocrine Neoplasms in the US

Arvind Dasari et al. JAMA Netw Open. .

Erratum in

  • Errors in Abstract and Figure 2.
    [No authors listed] [No authors listed] JAMA Netw Open. 2025 Nov 3;8(11):e2547077. doi: 10.1001/jamanetworkopen.2025.47077. JAMA Netw Open. 2025. PMID: 41191362 Free PMC article. No abstract available.

Abstract

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 243 896 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.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Dasari reported grants from BMS, Eisai, Enterome, Guardant Health, HutchMed, Natera, Neogenomics, Personalis, Taiho, Takeda, and Xencor; he reported receiving consulting fees from Advanced Accelerator Applications, Agenus, BMS, Crinetics, Illumina, Lantheus, Sanofi, Taiho, and Takeda outside the submitted work. Dr Wallace reported employment with Sirtex at the beginning of this project—she did not receive contribution for this work. Dr Halperin reported receiving consulting fees from Exelixis, Novartis, Crinetics, Camurus, Alphamedix, Chimeric, ITM, Amryt; he reported receiving grant support from ITM, Novartis, Rayzebio, ThermoFisher Scientific, and Camurus outside the submitted work. Dr Kunz reported receiving grant support from RayzeBio and Novartis; she reported receiving speaking honoraria from Natera, ITM, BMS, and Foundation Medicine; she reported honoraria from advisory board participation from Amgen, Genentech, Crinetics, and HutchMed, and Ipsen outside the submitted work. Dr Singh reported grants from Novartis and Ipsen, and consulting fees from Novartis, Ipsen, and Camurus outside the submitted work. Dr Chasen reported honoraria for advisory board participation from Advanced Accelerator Applications outside the submitted work. Dr Yao reported consulting fees from Acrotech, Advanced Accelerator Applications, Amgen, Chiasma, Crinetics, Exelixis, HutchMed, Ipsen, Sanofi, and TaiRx outside the submitted work. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Incidence Trends From 1975 to 2021
Figure 2.
Figure 2.. Limited Duration Prevalence of Neuroendocrine Neoplasms (NEN)
Figure 3.
Figure 3.. Median Overall Survival of Neuroendocrine Neoplasms
See this image and copyright information in PMC

References

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