Neuroendocrine liver metastases: a contemporary review of treatment strategies

Abstract

Well-differentiated neuroendocrine tumors (NETs) are globally increasing in prevalence and the liver is the most common site of metastasis. Neuroendocrine liver metastases (NELM) are heterogeneous in clinical presentation and prognosis. Fortunately, recent advances in diagnostic techniques and therapeutic strategies have improved the multidisciplinary management of this challenging condition. When feasible, surgical resection of NELM offers the best long-term outcomes. General indications for hepatic resection include performance status acceptable for major liver surgery, grade 1 or 2 tumors, absence of extrahepatic disease, adequate size and function of future liver remnant, and feasibility of resecting >90% of metastases. Adjunct therapies including concomitant liver ablation are generally safe when used appropriately and may expand the number of patients eligible for surgery. Among patients with synchronous resectable NELM, resection of the primary either in a staged or combined fashion is recommended. For patients who are not surgical candidates, liver-directed therapies such as transarterial embolization, chemoembolization, and radioembolization can provide locoregional control and improve symptoms of carcinoid syndrome. Multiple systemic therapy options also exist for patients with advanced or progressive disease. Ongoing research efforts are needed to identify novel biomarkers that will define the optimal indications for and sequencing of treatments to be delivered in a personalized fashion.

Keywords: Gastroenteropancreatic neuroendocrine tumors (GEP-NETs); carcinoid; hepatic resection; liver-directed therapies; targeted therapy.

Figure 1

Representative example of NELM on (A) arterial phase CT, (B) portal venous phase CT, and (C) ⁶⁸Ga-DOTATATE CT-PET. NELM, neuroendocrine liver metastases; CT, computed tomography; PET, positron emission tomography.

Figure 2

Representative example of ⁶⁸Ga-DOTATATE CT-PET demonstrating somatostatin receptor avid metastatic disease in the breast, peritoneum, bone, and lymph nodes in a patient with unremarkable CT imaging. CT, computed tomography; PET, positron emission tomography.

Figure 3

Proposed clinical pathway for managing patients with NELM based on the authors’ institutional experience. NELM, neuroendocrine liver metastases; PNET, pancreatic neuroendocrine tumor; TAE, transarterial embolization; XRT, radiation therapy; PRRT; peptide receptor radionuclide therapy; SSAs, somatostatin analogs.