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

Sequencing of Therapy

There is no consensus on the optimal sequencing of therapy in NETs. We recommend that the therapeutic plan be formulated according to patient and disease characteristics (Table 2; Figure 1) in partnership with the patient and a multidisciplinary team.

Figure 1.

aFor select cases. Schema for management of well-differentiated neuroendocrine tumors according to patient and tumor characteristics. CAPTEM, temozolomide plus capecitabine; epNET, extrapancreatic neuroendocrine tumor; pNET, pancreatic neuroendocrine tumor; SSA, somatostatin analog; SSTR, somatostatin receptor.

If a newly diagnosed patient has localized or oligometastatic disease that is resectable and the patient is a surgical candidate, it would be reasonable to proceed with resection and surveillance in conjunction with surgical oncology colleagues.

In considering systemic therapy for patients with metastatic or unresectable NETs, first-line treatment selection is guided by site of disease, volume of disease, grade, and pace of growth. For G1-G2 metastatic or unresectable NETs, we recommend considering whether immediate systemic therapy is indicated or if the patient can be observed with serial imaging. Reasons for starting treatment include functional tumor with symptoms of hormone excess, high burden of disease, and rapid rate of progression. For indolent or low-volume disease, SSAs are typically chosen as first-line systemic therapy. If a rapid tumor response is desired for well-differentiated NETs because of high grade, high tumor burden, or rapid growth, capecitabine and temozolomide can be considered for pNETs. Platinum-etoposide chemotherapy may be considered for G3 NETs. At time of disease progression on first-line therapy, in addition to consideration of primary site, burden, and pace of disease, SSTR status and comorbidities guide our decisions on how to structure the next lines of therapy. If the NET is SSTR-positive and the patient has good performance status without contraindications including renal and hepatic dysfunction, 177Lu-DOTATATE may be a good option for tumor control. Sunitinib, the only FDA-approved TKI in NETs, is approved for use in pNETs. TKIs are relatively contraindicated in heart disease, hypertension, and elevated bleeding risk. Everolimus is relatively contraindicated in severe pulmonary disease because of risk of developing interstitial lung disease and in poorly controlled diabetes as it can worsen glycemic control.

In the past decade, we have seen incredible advances in the field of NETs including new diagnostic tools and treatments for tumor control. Given that both the incidence and prevalence of NETs are increasing, the practicing oncologist will undoubtedly treat patients with NETs. However, the disease itself is heterogeneous, and treatment landscape is complex without clear lines of therapy. We remind the reader to keep in mind the six key patient and tumor characteristics that can guide treatment selection: hormone status, extent and burden of disease, grade, pace of growth, primary site, and SSTR status. We recognize the complexity of treating patients with NETs and we hope this clinical review has provided the reader with an approach to help tailor treatments.