Cancer-Specific Mortality Shows Variable Risk Throughout Neuroendocrine Tumors

The risk of cancer-specific death was significantly higher than the risk of noncancer death in patients with neuroendocrine tumors, despite the reported heterogeneity by primary tumor site.

The risk of cancer-specific death was significantly higher than the risk of noncancer death in patients with neuroendocrine tumors (NETs), despite the reported heterogeneity by primary tumor site, according to findings from a study published in the Journal of the National Comprehensive Cancer Network.1

At a median follow-up of 42 months (interquartile range, 17-82), the 5-year risk of cancer-specific death was higher vs the 5-year risk of noncancer death, at 27.3% (95% CI, 26.3%-28.4%) vs 5.6% (95% CI, 5.1%-6.1%), respectively. The 10-year risk was 34.5% (95% CI, 33.2%-35.8%) vs 10.3% (95% CI, 9.4%-11.3%), respectively.

However, the risk of noncancer death was higher vs the risk of cancer-specific death in nonmetastatic gastric, small intestine, colonic, and rectal NETs. Among all nonmetastatic NETs, the 5-year risk of cancer-specific death vs the 5-year risk of noncancer death was 7.7% (95% CI, 7.0%-8.6%)vs 6.2% (95% CI, 5.4%-6.9%), respectively. The 10-year risk was 11.7% (95% CI, 10.4%-13.2%) vs 10.2% (95% CI, 9.1%-11.3%), respectively.

“Our results show that some patients with nonmetastatic NETs are more likely to die of other causes than NET. This is crucial to inform patients and make decisions regarding treatment. It is important to make sure that treatment does not present a higher risk than the NET itself. For example, small pancreas, stomach, or rectal NETs can be safely monitored,” lead study author Julie Hallet, MD, MSc, an assistant professor in the Department of Surgery at the University of Toronto, said in a press release.2

Patients with NETs have prolonged overall survival, but the effects of cancer-specific and noncancer deaths on survival is not well defined.

“Neuroendocrine tumors are very unique in that they are often slow growing indolent cancers. They have very heterogenous behaviors. While some metastatic tumors can threaten patients’ survival, other localized tumors do not. Therefore, it was important to understand cause of death and the exact burden of cancer on mortality in different subgroups of patients with NETs,” said Hallet.

As such, investigators evaluated cancer-specific and noncancer death following NET diagnosis.

The population-based, retrospective cohort study included 8607 patients 18 years of age or older who had been diagnosed with NETs from January 1, 2001, through December 31, 2015.

A total of 3121 (36.3%) death events were recorded during follow-up, of which 2487 were because of cancer.

The most common primary tumor site was bronchopulmonary (22.8%), followed by the small intestine (19.3%) and the rectum (14.4%).

A total of 42.2% of patients had metastases, including synchronous metastases in 32.0% of cases. Most patients with rectal (90.8% and pancreatic NETs (70.7%) did not have metastases. Physicians diagnosed a non-NET cancer after NET diagnosis in 765 patients.

Competing risk methods were used to estimate the cumulative incidence of cancer-specific and noncancer death, which was stratified by primary NET site and metastatic status. Prognostic factors were evaluated with subdistribution hazard models (sHR).

Additional results showed a significantly higher number of cancer-specific deaths compared with noncancer deaths in patients with synchronous (sHR, 9.19; 95% CI, 8.16-10.36) and metachronous metastatic NETs (sHR, 6.55; 95% CI, 5.84-7.60).

By primary NET site, the highest risks of cancer-specific death were reported in bronchopulmonary (5-year: 36.4%; 95% CI, 34.2%-38.7%; 10-year: 42.7%; 95% CI, 0.1%-45.3%), pancreatic (5-year: 34.8%; 95% CI, 31.5%-38.2%; 10-year: 48.4%; 95% CI, 43.5%-53.0%), and colonic NETs (5-year: 21.4%; 95% CI, 18.9%-24.0%; 10-year: 26.6%; 95% CI, 23.4%-29.9%).

Advancing age, higher material deprivation, and metastases were independently associated with higher hazards of cancer-specific death, and female sex and high comorbidity index was associated with lower hazards of cancer-specific death.

“NETs are a very heterogeneous group of malignancies, so they require individualized treatment recommendations for each primary tumor site. It is insightful to learn about the different patterns of both cancer and non-cancer specific mortality specific to primary tumor site as well as other contributing factors. This article will be helpful to inform future guidelines regarding monitoring and treatment of different NETs and enable providers to provide NET site-specific counseling,” Whitney S. Goldner, MD; professor in the Division of Diabetes, Endocrinology, and Metabolism at the Fred & Pamela Buffett Cancer Center, and vice chair of the NCCN Guidelines Panel for Neuroendocrine Tumors; said in a press release.


  1. Hallet J, Law C, Singh S, et al. Risk of cancer-specific death for patients diagnosed with neuroendocrine tumors: a population-based analysis. J Natl Compr Canc Netw. Published online June 4, 2021. Accessed August 27, 2021. doi:10.6004/jnccn.2020.7666
  2. JNCCN study reveals neuroendocrine tumor mortality patterns to inform treatment decisions. News release. National Comprehensive Cancer Network. August 26, 2021. Accessed August 27, 2021.