Incidence of Lung Neuroendocrine Tumors Nearly Tripled Over Two Decades, Study Finds

A rare type of lung cancer is being diagnosed far more often than it was two decades ago, according to new population-based research from the University of Toronto. The study, published Oct. 2 in JAMA Network Open, found that the incidence of lung neuroendocrine neoplasms (NENs) increased nearly threefold in Ontario between 2000 and 2020. Survival outcomes also varied widely by tumor type and stage, highlighting the need for more personalized treatment and follow-up strategies.

Neuroendocrine neoplasms (NENs) are a group of rare tumors that begin in hormone-producing cells found throughout the body. When these tumors start in the lungs, they are called lung NENs and account for more than 20% of all neuroendocrine cancers.

Lung NENs include several types that behave very differently. The slower-growing forms are called typical and atypical neuroendocrine tumors (NETs), while the more aggressive ones are classified as large-cell or small-cell neuroendocrine carcinomas. Although neuroendocrine tumors of the digestive system have been widely studied, far less is known about those that develop in the lungs, even as their incidence appears to be on the rise.

Julie Hallet, M.D., M.Sc.

To address this gap, a retrospective cohort study was conducted by a team of researchers, led by Julie Hallet, M.D., M.Sc., assistant professor of surgery at the University of Toronto and Sunnybrook Health Sciences Centre. The researchers analyzed population-level data from ICES, a provincial health data repository. The cohort included 4,479 adults newly diagnosed with lung NENs between 2000 and 2020. The researchers used statistical models to examine incidence trends, overall survival (OS) and deaths specifically caused by lung cancer.

The analysis found that the annual incidence of lung NENs rose 2.87-fold, from 0.87 to 2.50 cases per 100,000 people. Most of the increase was attributed to typical (slower-growing) NETs and early-stage disease, particularly stage 1 tumors, which more than doubled in frequency. The median age at diagnosis was 67 years, and slightly more than half were female. About 25% of patients were diagnosed after their cancer had already spread to other parts of the body (stage 4).

Survival outcomes reflected the broad clinical spectrum of these tumors. Across all histologic types, the 5- and 10-year OS rates were 50% and 40%, respectively. However, outcomes differed sharply by tumor subtype and stage. People with slower-growing typical NETs and those diagnosed at earlier stages had the most favorable prognoses. In these groups, deaths from other causes eventually outnumbered deaths from lung cancer itself, beginning about two to three years after diagnosis.

Hallet and her colleagues also found that advancing age, lower socioeconomic status and higher stage at diagnosis were independently associated with worse survival. Lung cancer-specific deaths occurred in 41% of patients at five years and 46% at 10 years across the full cohort.

In their paper, the authors noted that their work adds one of the most comprehensive, contemporary population-based analyses to date, offering new insight into incidence trends and lung cancer-specific mortality.

According to the authors, the increase in incidence is probably multifactorial, driven by updated diagnostic tools, evolving pathology criteria and greater awareness of these tumors among clinicians. Many of the newly identified cancers are small and asymptomatic, they wrote, representing cases that may have gone undetected in the past.

They acknowledged that their study was limited by the use of routinely collected data, which may contain classification errors and lacked details such as lifestyle factors, race and ethnicity, or tumor grade.

Still, the researchers noted practical implications for clinical management. Because patients with typical NETs and early-stage disease often face a higher risk of dying from other causes, they recommended tailoring treatment intensity and follow-up schedules based on individual risk.

Hallet and colleagues concluded that further research should confirm these trends in broader populations. They also called for studies on patient-clinician communication about prognosis and on follow-up strategies that account for competing health risks.