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

Diagnostic Work-up

Diagnostic imaging for NETs should include anatomic and functional radiographic modalities. Anatomic imaging may use computed tomography or magnetic resonance imaging and should include the primary site of disease as well as multiphasic imaging of the liver as this is a common site of metastasis. Nearly 80% of well-differentiated NETs express the somatostatin receptor (SSTR) on the cell surface.[11] Per appropriate use criteria, nearly all patients with well-differentiated NETs should undergo SSTR imaging, including for staging purposes in patients with localized disease.[12] Options include 68Ga-DOTATATE positron emission tomography (PET), which was US Food and Drug Administration (FDA)–approved in 2016 and has supplanted 111In-diethylene triamine pentaacetic acid scintigraphy (Octreoscan) as the modality of choice for functional imaging in NETs,[13,14] or 64Cu-DOTATATE PET, which was FDA-approved in 2020 based on a phase III trial demonstrating sensitivity, specificity, and reliability.[15] Because of its longer half-life (12.7 hours v 1.1 hours for 68Ga-DOTATATE), 64Cu-DOTATATE may increase availability of functional imaging at local medical centers and improve access to care.[15] Lastly, 68Ga-DOTATOC was FDA-approved in 2019, although availability is limited in the United States.[16] Of note, radiotracer uptake in NETs does not seem to be altered by use of long-acting repeatable (LAR) somatostatin analogs (SSAs) for these newer PET imaging modalities.[17] FDG-PET scan may be considered along with SSTR PET imaging in G3 disease. FDG avidity may be a poor prognostic sign in well-differentiated G3 NETs, and positivity on either modality may guide the decision to use cytotoxic agents versus peptide receptor radionuclide therapy (PRRT).[18]

Two categories of peptides can be secreted by NETs and detected in the serum and urine. Hormonally inactive peptides, such as chromogranin A and pancreatic polypeptide, can serve as tumor markers for nonfunctioning NETs, although this use is controversial as the peptides may not be specific to the NET and values can fluctuate. Chromogranin A, for example, may be elevated in patients with hepatic and renal impairment and in patients taking proton-pump inhibitors.[19] Biochemically active hormones and neuropeptides secreted by NETs are specific to each functional tumor and should be evaluated on the basis of presenting symptoms; for instance, evaluation of serotonin secretion using 24-hour urine or plasma 5-HIAA is indicated for carcinoid syndrome.[9] Screening for hormone secretion in asymptomatic individuals is not routinely recommended.[9]