Survival of Patients With NETs May Depend on Primary Tumor Location

For patients with neuroendocrine tumors, the chances of dying of cancer were higher than dying of other causes, but mortality largely varies by primary tumor site.

For patients with neuroendocrine tumors (NETs), the chances of dying of cancer were higher than dying of other causes, but mortality largely varies by primary tumor site, according to retrospective data published in the Journal of the National Comprehensive Cancer Network.1

NETs are more prevalent than pancreatic, esophageal, and gastric cancers combined. However, data on mortality and cancer burden for patients with NETs remains scarce. NETs tend to have a unique biology and chronic behavior, setting them apart from other malignancies. Due to prolonged survival and frequent incidental findings, many patients may not die of NETs.

"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 sub-groups of patients with NETs," said lead author Julie Hallet, MD, MSc, of the University of Toronto, in a press release. issued by NCCN.2

The retrospective analysis used the Ontario Cancer Registry, Registered Persons Database, Ontario Health Insurance Plan, and the Ontario Registrar General Death database. Patients included were 18 years of age or older diagnosed with NETs from January 1, 2001 to December 31, 2015. In total, 8707 patients were identified. Ninety-one were excluded for being under 18 or over 105 years of age and 9 were excluded for have a date of death recorded before the date of NETs diagnosis. The final cohort included 8607 patients. At the median follow-up of 42 months, 36.3% of patients had died. Bronchopulmonary was the most common tumor site at 22.8%, then the small intestines (19.3%), and the rectum (14.4%). A non-NET cancer was diagnosed after a NET diagnosis in 765 patients. 

"Our results show that some patients with non-metastatic NETs are more likely to die of other causes than NETs. 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,” said Hallet.2

A little under half (42.2%) of patients had metastasis, and 32% had synchronous metastases. However, this varied depending on primary tumor site. For patients with rectal NETs, 90.8% of patients did not have metastasis. For patients with pancreatic NETs, 70.7% did not have NETs.

Patients were split into 4 age groups, <50 (21.6%), 50-59 (23.3%), 60-69 (25.9%), and ≥70 (29.2%). Female patients made up 50.2% of the analysis. Most of the patients identified were diagnosed between 2009-2015 (65.6%). The vast majority, 89.2%, of patients lived in urban areas and 72.2% had a low comorbidity burden.

For the entire cohort, the 5-year survival rate was 67.1% (95% CI, 66.0%–68.1%) and 55.1% at 10-years (95% CI, 53.6%–56.6%). The risk of cancer death at 5 years was 27.3% (95% CI, 26.3%–28.4%) and 34.5% at 10 years (95% CI, 33.2%–35.8%). This is significantly higher than the risk of non-cancer death at 5.6% at 5 years (95% CI, 5.1%–6.1%) and 10.3% at 10 years (95% CI, 9.4%–11.3%). Patients with bronchopulmonary NETs had the highest recorded risk of death, with 36.4% (95% CI, 34.2%–38.7%) at 5 years and 42.7% (95% CI, 0.1%–45.3%) at 10 years. Pancreatic NETs had the next highest risk of death at 34.8% ([95% CI, 31.5%–38.2%) at 5 years and 48.4% (95% CI, 43.5%–53.0%) at 10 years. For colonic NETs is was 21.4% (95% CI, 18.9%–24.0%) at 5 years and 26.6% (95% CI, 23.4%–29.9% at 10 years.

“Finally, examination of factors associated with cancer-specific and noncancer-related death showed that efforts to address cancer-specific death in NETs should include special considerations for older adults and socioeconomically deprived patients to ensure they can access and receive care throughout their cancer journey,” wrote Hallet et al, in the report. “The association of advancing age with an increased risk of cancer death may be related to underlying increased vulnerability and frailty, but also risks of de-escalating cancer care in older adults who are underrepresented in clinical studies. Patients with a higher level of deprivation are known to exhibit different health-seeking behaviors and experience delayed diagnosis and access to care, which impact outcomes.”

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. 2021; 19(8) doi:
2.JNCCN Study Reveals neuroendocrine tumor mortality patterns to inform treatment decisions. News release. August 26, 2021. Accessed August 30, 2021.