Is there still a role for the hepatic locoregional treatment of metastatic neuroendocrine tumors in the era of systemic targeted therapies?

Abstract

Gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) frequently present with distant metastases at the time of diagnosis and the liver is the most frequent site of spreading. The early identification of metastatic disease represents a major prognostic factor for GEP-NENs patients. Radical surgical resection, which is feasible for a minority of patients, is considered the only curative option, while the best management for patients with unresectable liver metastases is still being debated. In the last few years, a number of locoregional and systemic treatments has become available for GEP-NEN patients metastatic to the liver. However, to date only a few prospective studies have compared those therapies and the optimal management option is based on clinical judgement. Additionally, locoregional treatments appear feasible and safe for disease control for patients with limited liver involvement and effective in symptoms control for patients with diffuse liver metastases. Considering the lack of randomized controlled trials comparing the locoregional treatments of liver metastatic NEN patients, clinical judgment remains key to set the most appropriate therapeutic pathway. Prospective data may ultimately lead to more personalized and optimized treatments. The present review analyzes all the locoregional therapy modalities (i.e., surgery, ablative treatments and transarterial approach) and aims to provide clinicians with a useful algorithm to best treat GEP-NEN patients metastatic to the liver.

Keywords: Ablation; Chemoembolization; Gastroenteropancreatic neuroendocrine neoplasms; Liver metastases; Locoregional therapies; Systemic therapies.

Figure 1

Arteriography of voluminous liver metastases secondary to an ileal neuroendocrine neoplasms.

Figure 2

Computed tomography scan showing massive liver metastases in a patient with an ileal primary NET before (A) and after (B) transarterial chemoembolization procedure.

Figure 3

Treatment algorithm for advanced gastroenteropancreatic neuroendocrine tumors. ¹Resection of primary, no (or limited) extrahepatic disease. SSA: Somatostatin analog; IFN: Interferon; PRRT: Peptide receptor radionuclide therapy; TAE: Transarterial embolization; TACE: Transarterial chemoembolization; TARE: Transarterial radioembolization; RFA: Radiofrequency ablation.