During the past 4 decades, the incidence and prevalence of neuroendocrine tumors (NETs) have dramatically increased, but the researchers believe the increase is related to diagnostic advances.
The new finding is published online April 27 in JAMA Oncology.
In this population-based study that included 64,971 patients with NETs, the authors found that incidence jumped from 1.09 per 100,000 persons in 1973 to 6.98 per 100,000 by 2012.
The 20-year limited-duration prevalence also increased substantially, from 0.006% in 1993 to 0.048% in 2012 (P < .001).
However, the greatest increase has been in early-stage tumors, pointed out lead author, Arvind Dasari, MD, MS, from the University of Texas MD Anderson Cancer Center, Houston, in an audio interview posted on the JAMA website. "We believe the increase in incidence is due to advances in diagnostic modalities," Dr Dasari said. "The increased use of imaging explains the increased diagnosis in the lung and gastrointestinal tract, while increased use of endoscopy explains the increased incidence in sites such as the stomach and rectum."
Dr Dasari noted that the rise in incidence was observed across all cancer stages and all tumor grades, "but we did notice that it was more marked at certain sites, such as the stomach and rectum."
While the incidence and prevalence have increased, so has survival of patients with NET. Improved survival has been especially pronounced in distant gastrointestinal NETs and in distant pancreatic NETs, which reflects improved therapies for these cancers, explained Dr Dasari.
The study represents the largest epidemiologic study of NETs to date. The last study looking at incidence and prevalence was conducted in 2008 and used data up to 2004, so it was time for an update, said Dr Dasari. "Since then there have been improvements in diagnosis and management."
Call to Arms
The study used data from the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) database.
Despite limitations inherent to the SEER database, which include underreporting of NET cases to cancer registries, "the trends are real, likely underestimate the true burden of NETs, and are more pronounced than previously reported," comments Pamela L. Kunz, MD, from Stanford University, California, writing in an accompanying editorial.
The trends are real…[and] likely underestimate the true burden of NETs. Dr Pamela L. Kunz
She points out that the prevalence of NETs was estimated to be 171,321 cases in 2014, which is higher than the combined prevalence of other, more common gastrointestinal cancers, including esophageal cancer (36,857 patients), gastric adenocarcinoma (79,843 patients), and pancreatic adenocarcinoma (49,620 patients) (all 2013 estimates).
"NETs were once considered rare and unworthy of scientific study or funding," writes Dr Kunz. "The study by Dasari and colleagues and others have hopefully put this notion to rest and serve as our call to arms."
Incidence and Survival Higher but Varied
Dr Dasari and colleagues note that the increase in the incidence of NETs occurred across all sites, stages, and grades and ranged from a 15-fold increase in the stomach to a 2-fold increase in the cecum.
When categorized by age, the most dramatic rise in incidence was observed in patients 65 years or older and in those 50 to 64 years, who experienced a more than 8-fold rise in incidence. Younger patients had a more modest 3-fold increase in incidence.
Regarding survival, the median overall survival (OS) time for all patients was 9.3 years. Patients with localized NETs had better median OS (>30 years) than those with regional NETs (10.2 years) and distant NETs (12 months) (P < .001).
Categorized by grade groups, G1 NETs had the highest median OS (16.2 years); OS was worse for G2 NETs (8.3 years), and G3 and G4 NETs had the worst OS (10 months).
By cancer site, NETs in the rectum (OS, 24.6 years) and appendix (OS >30.0 years) had the best median OS, while NETs in the pancreas (OS, 3.6 years) and lung (OS, 5.5 years) had the worst median OS. All of the survival differences reached statistical significance (log-rank P < .001).
The study was supported by Novartis. Dr Dasari has received research support from Novartis, Ipsen, and Eisai and serves as a consultant for Novartis, Ipsen, and Lexicon. Several coauthors also report relationships with industry. Dr Kunz has received research funding to her institution from Advance Accelerator Applications, Dicerna, Esanex, Genentech, Ipsen, Lexicon Pharmaceuticals, Merck, and Oxigene. She has served on scientific advisory board meetings for and has received honoraria from Ipsen, Novartis, and Lexicon.