Contemporary Incidence and Survival of Lung Neuroendocrine Neoplasms.

Abstract

Importance: While the epidemiology of overall and gastrointestinal neuroendocrine neoplasms (NENs) has been reported, data specific to lung NENs remain scarce.

Objective: To examine the incidence, overall survival (OS), and lung cancer-specific death for lung NENs.

Design, setting, and participants: Population-based retrospective cohort study in Ontario, Canada, of adult patients with incident lung NENs from 2000 to 2020. Data were analyzed from July to December 2024.

Main outcomes and measures: Yearly incidence rates of lung NENs. OS examined with Kaplan-Meier curves and Cox regression models. Lung cancer-specific deaths using cumulative incidence function and Fine-Gray models accounting for the competing risk of death from other causes.

Results: Among 4479 total patients, the median (IQR) age at diagnosis was 67 (57-74) years, and 2521 (56.3%) were female; 2056 (45.9%) had typical neuroendocrine tumors (NET), 370 (8.3%) atypical NET, 998 (22.3%) large cell neuroendocrine carcinoma (NEC, including small cell and mixed NEC), and 1055 (23.6%) other NEC, as well as 1103 (24.6%) who presented as stage IV. The incidence of lung NENs increased 2.87-fold from 0.87 to 2.50 per 100 000 from 2000 to 2020. This rise in incidence was observed mostly for typical NET (from 0.51 to 1.09) and for stage I (0.68 to 1.18). With a median (IQR) follow-up of 34 (9-87) months, 5- and 10-year OS were 50% (95% CI, 49%-51%) and 40% (95% CI, 39%-41%) overall. Advancing age, lower socioeconomic status, type of lung NEN, and advancing stage were independently associated with inferior OS. Cumulative incidence of lung cancer-specific deaths was 41% (95% CI, 40%-42%) at 5 years and 46% (95% CI, 45%-47%) at 10 years. Advancing age, type of lung NEN, and increasing stage were independently associated with higher hazards of lung cancer-specific deaths. Lung cancer-specific deaths were exceeded by deaths from other causes starting 2 year after diagnosis for typical NET and 3 years after diagnosis for stage I disease.

Conclusions and relevance: The incidence of lung NENs has increased over 20 years, mostly associated with stage I disease. Prolonged OS was observed after lung NEN diagnosis. Patients with typical lung NET and stage I disease were more likely to die of causes other than lung cancer after 1 and 3 years, respectively. These data are important to direct efforts in care, research, and patient counseling.