Neuroendocrine liver metastases treatment strategies: a viewpoint.

Abstract

| https://dx.doi.org/10.21037/hbsn-21-178 I read with great interest the article “Neuroendocrine liver metastases: a contemporary review of treatment strategies” (1) published in Hepatobiliary Surgery and Nutrition as it is focused on a debate topic. The majority of gastro-entero-pancreatic neuroendocrine neoplasms (GEP-NENs) metastasize to the liver, being the presence of liver metastases (NELM) a negative prognostic factor. There is still controversy regarding the optimal management of patients with NELM. Surgery plays a key-role role as, indeed, the resection of the primary tumor and its metastases remains, when possible, the only curative treatment in patients with GEPNENs. Surgical resection with curative intent is reserved to patients with no or minimum extra-hepatic disease and with limited tumor burden and, even if no randomized controlled trials are available comparing surgery versus non-surgical therapies, resection of NELM is reported to be associated with excellent long-term outcomes and should be the preferred treatment option for patients with NELM (1). Although still controversial, debulking surgery is suggested if at least 80–90% of tumor load can be removed with promising results in terms of both overall survival (OS), with a reported 5-year OS of 60%, and symptom control; some authors have also proposed to modify the threshold for considering cytoreductive surgery to a 70% threshold (1). In metastatic cases not amenable to surgery because of disease’s extent or patient’s co-morbidities, liver-directed therapies represent a viable option to improve progressionfree survival (PFS) and to control hormonal symptoms. However, prospective studies comparing the different transarterial treatment strategies are scanty and decisions regarding liver-directed therapies have traditionally been related to institutional preferences and local expertise. Several medical options are also available for advanced metastatic NENs and these include somatostatin analogs (SSAs) as first-line treatment for tumor growth and symptom’s control, targeted therapies (i.e., everolimus and sunitinib), chemotherapy mainly for G3 neoplasms and pancreatic forms and peptide receptor radionuclide therapy (PRRT), which demonstrated improved PFS compared with high-dose SSA among patients with midgut NENs and has been repeatedly reported as particularly useful for symptom relief in functioning forms. In highly selected cases (<1%), liver transplant (LT) might be considered in patients with NELM representing a potential chance of radical cure if proper patient selection is provided. Satisfactory long-term outcomes have been reported and, in the only available comparative study, a survival benefit of nearly 3.5 years at 10 years in favor of LT versus non-transplant strategies was observed (2). However, results are still heterogeneous with some studies suggesting similar survival outcomes among patients within Milan criteria who undergo surgical resection compared to LT (3). Although post-LT recurrence is observed in 30–50% of the cases, excellent long-term survival is observed after postLT NEN recurrence, especially when recurrence appears late after transplant, and an aggressive surgical treatment might result in a new chance of cure for selected patients (4). Considered the favourable long-term outcomes after LT, some authors suggested to adopt criteria that are less restrictive to not deny the patient’s access to a definitive Viewpoint