{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T18:13:53Z","timestamp":1792088033986,"version":"4.4.0"},"reference-count":30,"publisher":"MDPI AG","issue":"20","license":[{"start":{"date-parts":[[2025,10,15]],"date-time":"2025-10-15T00:00:00Z","timestamp":1760486400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Importance: Neuroendocrine tumors (NETs) have traditionally been considered rare (orphan) diseases; however, improvements in diagnostic methods and heightened awareness about NETs may have altered their epidemiologic profile in the U.S. Objective: To evaluate trends in incidence, prevalence, and survival of NETs in the United States from 2000 to 2021 using updated data from the SEER-22 registry. Method: This population-based, retrospective cohort study used the SEER-22 database for incidence, prevalence, and survival analyses. Data included 231,659 patients diagnosed with NETs between 2000 and 2021. Age-adjusted incidence, limited-duration prevalence, 5-year overall survival (OS), and hazard ratios (HRs) for survival by grade, stage, year of diagnosis, race, and primary site were investigated. Results: From 2000 to 2021, NET incidence nearly doubled, from 4.6 to 8.2 per 100,000 persons. The prevalence in 2021 reached 0.064%, with grade 1 tumors showing the steepest increase. Five-year OS was 77.4% overall and highest among localized NETs (82.3%) and grade 1 tumors (80.0%). Multivariable analysis showed improved survival over time (HR for 2015\u20132021 vs. 2000\u20132004, 0.92; 95% CI, 0.89\u20130.95). Black and American Indian\/Alaska Native patients had significantly worse outcomes than White patients. Conclusions and Relevance: NETs are no longer orphan diseases based on current U.S. incidence and prevalence trends. With increasing survival and patient numbers, there is an urgent need for expanded multidisciplinary NET care and research efforts focused on survivorship and quality of life.<\/jats:p>","DOI":"10.3390\/cancers17203323","type":"journal-article","created":{"date-parts":[[2025,10,15]],"date-time":"2025-10-15T11:57:42Z","timestamp":1760529462000},"page":"3323","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Dethroning of Neuroendocrine Tumor as an Orphan Disease: US Incidence, Prevalence, and Survival in the 21st Century"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9774-9226","authenticated-orcid":false,"given":"Qian","family":"Yu","sequence":"first","affiliation":[{"name":"Vascular and Interventional Radiology, Department of Radiology, University of Chicago Medical Center, University of Chicago, Chicago, IL 60637, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4999-458X","authenticated-orcid":false,"given":"Fan","family":"Cao","sequence":"additional","affiliation":[{"name":"School of Medicine, Georgetown University, Washington, DC 20007, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8537-6397","authenticated-orcid":false,"given":"Peter","family":"Hosein","sequence":"additional","affiliation":[{"name":"Division of Hematology\/Oncology, University of Miami Miller School of Medicine, Miami, FL 33136, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bin","family":"Huang","sequence":"additional","affiliation":[{"name":"Division of Cancer Biostatistics, Department of Internal Medicine, University of Kentucky College of Medicine, Lexington, KY 40536, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8502-835X","authenticated-orcid":false,"given":"Paulo S.","family":"Pinheiro","sequence":"additional","affiliation":[{"name":"Division of Epidemiology & Population Health Sciences, Department of Public Health Sciences, University of Miami School of Medicine, Miami, FL 33136, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6974-5815","authenticated-orcid":false,"given":"Yating","family":"Wang","sequence":"additional","affiliation":[{"name":"Hematology and Oncology, Ascension All Saints Hospital Cancer Center, Racine, WI 53405, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9710-4030","authenticated-orcid":false,"given":"Jaydira","family":"Del Rivero","sequence":"additional","affiliation":[{"name":"Center for Cancer Research, National Cancer Institute, Bethesda, MD 20814, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gilberto","family":"Lopes","sequence":"additional","affiliation":[{"name":"Sylvester Comprehensive Cancer Center, University of Miami Health System, Miami, FL 33136, USA"},{"name":"Division of Medical Oncology, Department of Medicine, University of Miami Miller School of Medicine, Miami, FL 33136, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aman","family":"Chauhan","sequence":"additional","affiliation":[{"name":"Sylvester Comprehensive Cancer Center, University of Miami Health System, Miami, FL 33136, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"3063","DOI":"10.1200\/JCO.2007.15.4377","article-title":"One hundred years after \u201ccarcinoid\u201d: Epidemiology of and prognostic factors for neuroendocrine tumors in 35,825 cases in the United States","volume":"26","author":"Yao","year":"2008","journal-title":"J. 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