In the Journals

Incidence, prevalence of neuroendocrine tumors on the rise

Incidence and prevalence of neuroendocrine tumors are steadily rising, possibly due to better detection of early-stage disease and stage migration, according to a retrospective, population-based study published in JAMA Oncology.

“We found that age-adjusted annual incidence of neuroendocrine tumors increased from 1.09 per 100,000 [individuals] in 1973 to 6.98 per 100,000 in 2012, a 6.4-fold increase,” Arvind Dasari, MD, MS, assistant professor of gastrointestinal oncology at The University of Texas MD Anderson Cancer Center, told HemOnc Today. “This is mostly for early-stage, low-grade tumors, especially in those over 65 years.”

Arvind Dasari

Dasari said these data should put to rest theories that neuroendocrine tumors are rare.

“In fact, the 20-year limited duration prevalence of neuroendocrine tumors was estimated to be over 171,000, making this tumor type the most commonly prevalent gastrointestinal malignancy, second to colorectal cancer,” Dasari said. “Significant improvements in survival were noted for neuroendocrine tumors, especially so for distant stage gastrointestinal and pancreatic neuroendocrine tumors, probably reflecting improvement in systemic therapies.

“These striking improvements for distant-stage disease will continue to improve as the dataset used in the study could not fully account for recent approvals of several drugs,” Dasari added. “Although all these findings were somewhat expected, the magnitude of change in incidence, prevalence and improvements in survival were surprising.”

Given the indolent clinical course of neuroendocrine tumors, their epidemiology is best studied in large, population-based registries with long follow-up, according to the researchers. Thus, they used the SEER database to comprehensively evaluate the demographic, clinical and prognostic features of neuroendocrine tumors in 64,971 patients (52.7% women) diagnosed from 1973 to 2012.

The researchers used associated population data to determine annual age-adjusted incidence, limited-duration prevalence and 5-year OS rates. They evaluated survival trends from 2000 to 2012 for the entire cohort, as well as specific subgroups, including distant-stage gastrointestinal neuroendocrine tumors and pancreatic neuroendocrine tumors.

Incidence, prevalence and OS served as primary endpoints.

The age-adjusted incidence rate increased from 1.09 per 100,000 individuals in 1973 to 6.98 per 100,000 across all sites, stages and grades.

The most dramatic rise in incidence was noted in patients aged 65 years or older (25.3 per 100,000) and in those aged 50 to 64 years (14.3 per 100,000). Those aged younger than 50 years had a modest rise to 1.75 per 100,000.

The highest incidence rates from 2000 to 2012 were in the gastroenteropancreatic sites (3.56 per 100,000) and lung (1.49 per 100,000); 0.84 per 100,000 had neuroendocrine tumors with an unknown primary site.

The 20-year limited-duration prevalence of neuroendocrine tumors increased substantially from 0.006% in 1993 to 0.048% in 2012 (P < .001). The projected prevalence was 171,321 cases on Jan. 1, 2014.

Median OS for all patients was 9.3 years. Localized neuroendocrine tumors had longer median OS (> 30 years) than regional neuroendocrine tumors (10.2 years) and distant neuroendocrine tumors (12 months; P < .001).

Of those with known grades, grade 1 neuroendocrine tumors had the longest median OS (16.2 years) compared with grade 2 (8.3 years), and grades 3 and 4 (10 months).

Median OS was longest for neuroendocrine tumors located in the rectum (24.6 years) and appendix (> 30 years) and shortest for those in the pancreas (3.6 years) and lung (5.5 years; P < .001).

The OS rate for all neuroendocrine tumors improved from 2000-2004 to 2009-2012 (HR = 0.79; 95% CI, 0.73-0.85). Greater OS increases occurred in distant-stage gastrointestinal neuroendocrine tumors (HR = 0.71; 95% CI, 0.62-0.81) and distant-stage pancreatic neuroendocrine tumors (HR = 0.56; 95% CI, 0.44-0.7) between those periods.

The steady rise in incidence of neuroendocrine tumors could be attributed to an increased diagnosis of asymptomatic, early-stage disease, Dasari and colleagues wrote. They noted the rise in incidence of the stomach (15-fold) and rectum (9-fold) may be associated with increased use of endoscopic procedures. The increase in incidence in the lung and small intestine sites may be linked to increased use of imaging procedures.

“Because prevalence rates include patients irrespective of whether they are under treatment or considered cured, they are a composite of the incidence and survival rates — the rise in prevalence in large part is probably largely due to increased incidence of early-stage, indolent tumors and to a lesser extent improvements in imaging — such as OctreoScans [Mallinckrodt Nuclear Medicine] — and systemic therapies, such as somatostatin analogues, thus improving survival for patients with advanced disease,” Dasari said.

It is unknown whether all tumors need to be surgically removed irrespective of site, size, grade or other biological factors, especially in patients with comorbidities, Dasari said. Risk factors associated with recurrence after curative surgery and appropriate surveillance practices to detect such recurrences also is unclear.

“The incidence of lung neuroendocrine tumors is rising very sharply and is likely going to continue to rise due to use of CT scans for lung cancer screening and other purposes,” Dasari said. “However, currently, there is only one FDA–approved drug for this subset, and this is clearly an unmet need. And, in contrast to well-differentiated neuroendocrine tumors, poorly differentiated neuroendocrine carcinomas have dismal outcomes, and these patients desperately need novel therapies to improve survival.”

With an estimated 171,321 cases in 2014, the prevalence of neuroendocrine tumors was higher than the combined estimated prevalence of esophageal cancer (n = 36,857), gastric adenocarcinoma (n = 79,843) and pancreatic adenocarcinoma (n = 49,620) in 2013, Pamela L. Kunz, MD, assistant professor of medicine at Stanford University Medical Center, wrote in an accompanying editorial.

“Neuroendocrine tumors were once considered rare and unworthy of scientific study or funding,” Kunz wrote. “The study by Dasari and colleagues and others have, hopefully, put this notion to rest and serve as our call to arms.”

“Neuroendocrine tumors need to be acknowledged as a much larger public health problem than previously recognized,” Kunz wrote. “We now need to conduct rigorous basic, translational, clinical, and health services research to move the field forward.”– by Chuck Gormley


For more information:
Arvind Dasari, MD, MS,
can be reached at Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Unit 426, Houston, TX 77030; email: adasari@mdanderson.org.

Disclosure: Novartis funded this study. Dasari reports research funding from Novartis, Ipsen, and Eisai; and consultant roles with Novartis, Ipsen and Lexicon. Please see the full study for a list of all other researchers’ relevant financial disclosures.

Incidence and prevalence of neuroendocrine tumors are steadily rising, possibly due to better detection of early-stage disease and stage migration, according to a retrospective, population-based study published in JAMA Oncology.

“We found that age-adjusted annual incidence of neuroendocrine tumors increased from 1.09 per 100,000 [individuals] in 1973 to 6.98 per 100,000 in 2012, a 6.4-fold increase,” Arvind Dasari, MD, MS, assistant professor of gastrointestinal oncology at The University of Texas MD Anderson Cancer Center, told HemOnc Today. “This is mostly for early-stage, low-grade tumors, especially in those over 65 years.”

Arvind Dasari

Dasari said these data should put to rest theories that neuroendocrine tumors are rare.

“In fact, the 20-year limited duration prevalence of neuroendocrine tumors was estimated to be over 171,000, making this tumor type the most commonly prevalent gastrointestinal malignancy, second to colorectal cancer,” Dasari said. “Significant improvements in survival were noted for neuroendocrine tumors, especially so for distant stage gastrointestinal and pancreatic neuroendocrine tumors, probably reflecting improvement in systemic therapies.

“These striking improvements for distant-stage disease will continue to improve as the dataset used in the study could not fully account for recent approvals of several drugs,” Dasari added. “Although all these findings were somewhat expected, the magnitude of change in incidence, prevalence and improvements in survival were surprising.”

Given the indolent clinical course of neuroendocrine tumors, their epidemiology is best studied in large, population-based registries with long follow-up, according to the researchers. Thus, they used the SEER database to comprehensively evaluate the demographic, clinical and prognostic features of neuroendocrine tumors in 64,971 patients (52.7% women) diagnosed from 1973 to 2012.

The researchers used associated population data to determine annual age-adjusted incidence, limited-duration prevalence and 5-year OS rates. They evaluated survival trends from 2000 to 2012 for the entire cohort, as well as specific subgroups, including distant-stage gastrointestinal neuroendocrine tumors and pancreatic neuroendocrine tumors.

Incidence, prevalence and OS served as primary endpoints.

The age-adjusted incidence rate increased from 1.09 per 100,000 individuals in 1973 to 6.98 per 100,000 across all sites, stages and grades.

The most dramatic rise in incidence was noted in patients aged 65 years or older (25.3 per 100,000) and in those aged 50 to 64 years (14.3 per 100,000). Those aged younger than 50 years had a modest rise to 1.75 per 100,000.

The highest incidence rates from 2000 to 2012 were in the gastroenteropancreatic sites (3.56 per 100,000) and lung (1.49 per 100,000); 0.84 per 100,000 had neuroendocrine tumors with an unknown primary site.

The 20-year limited-duration prevalence of neuroendocrine tumors increased substantially from 0.006% in 1993 to 0.048% in 2012 (P < .001). The projected prevalence was 171,321 cases on Jan. 1, 2014.

Median OS for all patients was 9.3 years. Localized neuroendocrine tumors had longer median OS (> 30 years) than regional neuroendocrine tumors (10.2 years) and distant neuroendocrine tumors (12 months; P < .001).

Of those with known grades, grade 1 neuroendocrine tumors had the longest median OS (16.2 years) compared with grade 2 (8.3 years), and grades 3 and 4 (10 months).

Median OS was longest for neuroendocrine tumors located in the rectum (24.6 years) and appendix (> 30 years) and shortest for those in the pancreas (3.6 years) and lung (5.5 years; P < .001).

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The OS rate for all neuroendocrine tumors improved from 2000-2004 to 2009-2012 (HR = 0.79; 95% CI, 0.73-0.85). Greater OS increases occurred in distant-stage gastrointestinal neuroendocrine tumors (HR = 0.71; 95% CI, 0.62-0.81) and distant-stage pancreatic neuroendocrine tumors (HR = 0.56; 95% CI, 0.44-0.7) between those periods.

The steady rise in incidence of neuroendocrine tumors could be attributed to an increased diagnosis of asymptomatic, early-stage disease, Dasari and colleagues wrote. They noted the rise in incidence of the stomach (15-fold) and rectum (9-fold) may be associated with increased use of endoscopic procedures. The increase in incidence in the lung and small intestine sites may be linked to increased use of imaging procedures.

“Because prevalence rates include patients irrespective of whether they are under treatment or considered cured, they are a composite of the incidence and survival rates — the rise in prevalence in large part is probably largely due to increased incidence of early-stage, indolent tumors and to a lesser extent improvements in imaging — such as OctreoScans [Mallinckrodt Nuclear Medicine] — and systemic therapies, such as somatostatin analogues, thus improving survival for patients with advanced disease,” Dasari said.

It is unknown whether all tumors need to be surgically removed irrespective of site, size, grade or other biological factors, especially in patients with comorbidities, Dasari said. Risk factors associated with recurrence after curative surgery and appropriate surveillance practices to detect such recurrences also is unclear.

“The incidence of lung neuroendocrine tumors is rising very sharply and is likely going to continue to rise due to use of CT scans for lung cancer screening and other purposes,” Dasari said. “However, currently, there is only one FDA–approved drug for this subset, and this is clearly an unmet need. And, in contrast to well-differentiated neuroendocrine tumors, poorly differentiated neuroendocrine carcinomas have dismal outcomes, and these patients desperately need novel therapies to improve survival.”

With an estimated 171,321 cases in 2014, the prevalence of neuroendocrine tumors was higher than the combined estimated prevalence of esophageal cancer (n = 36,857), gastric adenocarcinoma (n = 79,843) and pancreatic adenocarcinoma (n = 49,620) in 2013, Pamela L. Kunz, MD, assistant professor of medicine at Stanford University Medical Center, wrote in an accompanying editorial.

“Neuroendocrine tumors were once considered rare and unworthy of scientific study or funding,” Kunz wrote. “The study by Dasari and colleagues and others have, hopefully, put this notion to rest and serve as our call to arms.”

“Neuroendocrine tumors need to be acknowledged as a much larger public health problem than previously recognized,” Kunz wrote. “We now need to conduct rigorous basic, translational, clinical, and health services research to move the field forward.”– by Chuck Gormley


For more information:
Arvind Dasari, MD, MS,
can be reached at Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Unit 426, Houston, TX 77030; email: adasari@mdanderson.org.

Disclosure: Novartis funded this study. Dasari reports research funding from Novartis, Ipsen, and Eisai; and consultant roles with Novartis, Ipsen and Lexicon. Please see the full study for a list of all other researchers’ relevant financial disclosures.