Comment on Lai et al. Liver Transplantation for the Cure of Neuroendocrine Liver Metastasis: A Systematic Review with Particular Attention to the Risk Factors of Death and Recurrence.

Gastrointestinal neuroendocrine tumors (GI-NETs) are being diagnosed with increasing frequency and often manifest with liver metastases, presenting considerable therapeutic challenges. This commentary addresses the systematic review by Lai et al., which evaluated liver transplantation (LT) for NET-associated liver metastases (NEN-LM). Although Lai et al. identified LT as a promising intervention for unresectable or liver-confined NETs, we believe that certain aspects warrant further discussion. To begin with, approximately 16% of reported cases had an unknown primary tumor. This not only complicates patient selection and potentially introduces confounding outcomes but also contradicts the notion of "liver-limited disease". Furthermore, elevated proliferative activity, as indicated by a Ki-67 index of >2%, has been correlated with reduced survival rates. Therefore, LT should ideally be offered to patients with GI-NETs with a Ki-67 index of <2%. This subgroup of patients may also benefit from alternative therapy options, such as cytoreductive surgery/tumor debulking combined with peptide receptor radionuclide therapy (PRRT), which has demonstrated favorable outcomes and deserves greater attention. Finally, advocating LT for patients with NEN-LM based on retrospective data might facilitate its overuse, especially in countries/regions where living donor LT is employed. We believe that this important yet missing point merits an in-depth examination of its advantages and disadvantages.