Making Sense of a Complex Disease

A Practical Approach to Managing Neuroendocrine Tumors

Janie Y. Zhang, MD; Pamela L. Kunz, MD


J Oncol Pract. 2022;18(4):258-264. 

In This Article

Abstract and Introduction


Neuroendocrine tumors (NETs) are a heterogeneous clinical entity with a broad range of grade, pace of disease, functional status, and primary sites. Pathologic classification, diagnostic modalities, and therapeutic options for NETs have evolved considerably in the past decade. In part driven by these advances, incidence and prevalence of NETs are rising in the United States and the practicing oncologist is likely to encounter these in the clinic. However, there are no clear lines of therapy for unresectable or metastatic NETs, and sequencing of systemic therapies depends on consideration of patient and tumor characteristics including extent of disease, grade, pace of growth, functional status, primary site, somatostatin receptor status, performance status, and comorbidities. Familiarity with ongoing clinical trials will guide therapeutic decision making as well. In this review, we seek to provide a framework to formulate and tailor an individualized treatment plan for each patient with a NET.


Neuroendocrine neoplasms (NENs) are a diverse and heterogeneous clinical entity with a broad range of grade, differentiation, functional status, and primary sites. Of note, the term neuroendocrine tumor (NET) generally refers to well-differentiated disease, neuroendocrine carcinoma (NEC) refers to poorly differentiated disease, and NEN is an umbrella term inclusive of both. This review will focus on tumor control in NETs.

Both incidence and prevalence of NETs are rising in the United States. Annual age-adjusted incidence of NETs was 1.09 per 100,000 persons in 1973 and 6.98 per 100,000 persons in 2012. A similar trend is seen in the prevalence of NETs, with 20-year limited-duration prevalence increasing from 0.006% in 1993 to 0.048% in 2012.[1] Rising incidence may be because of greater detection of early-stage disease, with improved imaging techniques and universal use of staging and grading classifications, whereas increasing prevalence is likely because of improvement in systemic therapies and improved survival over time.[1] Overall survival (OS) in NETs is quite variable depending on grade and extent of disease, but generally NETs are more indolent than their adenocarcinoma counterparts, with median OS of 9.3 years.[1] Thus, despite their rarity, the practicing oncologist can expect to encounter cases of NETs in the clinic.