Hepatocellular carcinoma: when is liver transplantation oncologically futile?

Selection criteria of patients with hepatocellular carcinoma (HCC) for liver transplantation (LT) have been progressively expanded since the introduction of the Milan criteria. Transplanting patients with unfavourable tumor characteristics increases the risk of tumor recurrence and impacts post-transplant survival. Although tumor number and size are the basis of widely accepted selection criteria and correlate with tumor grading and microvascular invasion, stronger predictors of tumor recurrence have been recently identified. These surrogates of aggressive tumor biology include non-response to pre-transplant treatment, rapid recurrence within the first months after treatment, increased alpha-fetoprotein (AFP) concentrations, 18F-FDG positron emission tomography (PET) positive HCCs and poor differentiation and microvascular invasion in histology. The presence of any of these risk factors significantly increases the risk of tumor recurrence in patients within and beyond the Milan criteria. Especially the combination of two or more of these factors is associated with an inacceptably high recurrence risk and can render LT oncologically futile even in patients not exceeding the Milan criteria. In contrast, in absence of these risk factors also patients exceeding expanded selection criteria may undergo LT with low recurrence risk and favourable post-transplant outcome. In selected cases this may even be applicable to patients with macrovascular invasion, who are conventionally excluded from LT. The main focus of this article is to review LT for HCC in the light of recurrence rates and to explore at what tumor stage transplantation becomes futile.