Liver resection and transplantation for metastases from gastroenteropancreatic neuroendocrine tumors

Around 60% of gastroenteropancreatic neuroendocrine tumors (GEP-NETs) present liver metastases (NELM), which highly impact on prognosis. Treatment options for NELM mainly depend on the liver disease burden. In this review we propose a treatment algorithm for NELM with disease extension within the interest of liver resection (LR) and liver transplantation (LT). Preliminary resection of the primary and all the extrahepatic disease eases the access to liver-directed treatments and possibly confers a prognostic advantage. Solitary and oligometastatic disease deemed resectable with a conventional surgical commitment should be treated by LR. Despite the prognostic advantage of LR as compared to non-surgical options (80% 5-year overall survival [OS]) and the potential for cure, LR is burdened by high rates of recurrence (40% 5-year recurrence-free survival [RFS]). Neoadjuvant strategies by systemic and locoregional therapies may improve patient selection, especially in cases of borderline resectable NELM. In such patients, the oncological advantage of LR should be weighed against the high surgical risks and has to be preceded by a risk-benefit assessment. In young patients (<55 years) with G1/G2 unresectable NELM limited to <50% of the liver and no extrahepatic disease (Milan-NET criteria), LT may be considered. Patient selection is instrumental for good long-term outcomes (89% 10-year OS). The survival benefit increases over time with respect to non-transplant options. For patients exceeding the Milan-NET criteria, locoregional treatments can downstage the disease and occasionally allow LT. In G3 NETs and in cases not responding to liver-directed treatments, a systemic approach is usually warranted; debulking surgery can be considered in syndromic patients.