Incidence and Survival of Gastro-Entero-Pancreatic Neuroendocrine Neoplasms in the Contemporary Era.

Importance: Diagnostic practices, awareness, and care delivery for gastro-entero-pancreatic neuroendocrine neoplasms (GEP-NENs) have evolved substantially. Contemporary epidemiologic data are needed to inform clinical practice and health-system planning. Objective: To examine trends in incidence, overall survival (OS), and cancer-specific survival (CSS) for GEP-NENs over the past 2 decades. Design, Setting, and Participants: This population-based, retrospective cohort study using linked administrative datasets included adults diagnosed with incident GEP-NENs in Ontario, Canada (2000-2023), with analysis from July to December 2025. Exposure: New diagnosis of a GEP-NEN, stratified by site (appendix, colon, pancreas, rectum, small intestine, or stomach). Main Outcomes and Measures: Annual incidence per 100 000 population was calculated. OS was estimated using Kaplan-Meier methods; CSS was estimated using cumulative incidence functions treating noncancer deaths as a competing risk. Factors associated with OS and CSS were assessed using multivariable Cox and Fine-Gray regression models, respectively. Results: Among 12 877 individuals diagnosed with GEP-NENs with a median (IQR) age of 61 (50-71) years, 6228 (48.4%) were female. Synchronous metastases were present in 2313 individuals (16.5%). Overall incidence increased from 1.83 to 7.46 per 100 000 between 2000 and 2023. Incidence was highest for small intestine primaries, followed by rectum, pancreas, appendix, stomach, and colon. The increase was almost entirely due to nonmetastatic disease (1.48 to 7.18 per 100 000 per year, a 6.5-fold rise), with minimal change in metastatic presentations. The largest site-specific increases occurred in gastric and pancreatic NENs. Ten-year OS for all GEP-NENs was 63.3% (95% CI, 62.3%-64.3%). Ten-year CSS was 76.4% (95% CI, 75.6%-77.3%) for all GEP-NENs. CSS exceeded 90.0% at 10 years for patients without metastases at diagnosis but was 51.3% (95% CI, 49.7%-52.8%) for those with metastases at diagnosis. Survival estimates varied by primary tumor site, with most favorable outcomes for rectal and appendiceal NENs and least favorable for colonic and pancreatic NENs. Advancing age, lower socioeconomic status, and metastases at diagnosis were independently associated with worse OS and CSS, whereas female sex was associated with superior OS and CSS. Conclusions and Relevance: This cohort study of GEP-NENs found that incidence has continued to rise, largely due to increased diagnosis of nonmetastatic disease; OS and CSS were good but heterogeneous, influenced by demographic and disease-specific factors. These contemporary, population-based estimates provide essential evidence to support patient counselling, survivorship planning, health-system resource allocation, and the design of future NEN research.