Dethroning of Neuroendocrine Tumor as an Orphan Disease: US Incidence, Prevalence, and Survival in the 21st Century

<b>Importance:</b> 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. <b>Objective:</b> 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. <b>Method:</b> 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. <b>Results:</b> 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 2015-2021 vs. 2000-2004, 0.92; 95% CI, 0.89-0.95). Black and American Indian/Alaska Native patients had significantly worse outcomes than White patients. <b>Conclusions and Relevance:</b> 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.