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

Surgery and Local Therapies

If possible, localized low- and intermediate-grade NETs should be resected with negative margins, and lymph node resection should be considered in most cases.[9] There is currently no prospective data supporting adjuvant systemic therapy in well-differentiated NETs. SWOG 2104, a randomized phase II clinical trial of adjuvant capecitabine and temozolomide versus observation for high-risk, resected pNETs, is in development. Surveillance for disease recurrence after definitive surgery consists of imaging, often magnetic resonance imaging scans for younger patients to avoid chronic radiation exposure, for up to 10 years as time to recurrence may be long. An Ontario cohort of 936 patients reported median time to recurrence of 8.7 years in small-intestine NETs and 7.2 years in pNETs.[20] NCCN recommends surveillance imaging every 12–24 months after the first year for extrapancreatic NETs (epNETs) and every 6–12 months for pNETs, up to 10 years, whereas a 22-member consensus panel recommended yearly imaging for 3 years followed by imaging every 1–2 years up to 10 years.[9,21] Certain low-risk groups, such as patients with grade 1, lymph node–negative disease, may not warrant follow-up, whereas patients with high Ki-67 index or positive nodes may need more frequent follow-up.[21] Lastly, the use of biomarkers such as chromogranin A to assess for recurrence is controversial and was not recommended by the panel.[21]

Surgery and other local therapies have limited roles in the management of advanced NETs. In patients with limited metastatic disease for whom complete primary tumor resection and metastasectomy are possible, for example, pNETs metastatic to the liver, long-term survival has been described.[22] Liver-directed therapies, including surgical resection of a hepatic tumor, hepatic arterial embolization, and percutaneous thermal ablation, may be considered for patients who are progressing on systemic therapy and symptomatic from liver disease, or as debulking therapy for a high burden of disease in the liver.[23] Multiple techniques for hepatic embolotherapy are currently in practice and the optimal technique is unknown. The RETNET trial (NCT02724540), an ongoing prospective, open-label, multicenter, randomized study, is comparing bland embolization, lipiodol chemoembolization, or drug-eluting microsphere chemoembolization in patients with progressive or symptomatic unresectable NET liver metastases to address this question. As of this writing, the drug-eluting microsphere arm was closed early because of an increased number of perioperative complications.