Hepatocellular cancer as indication for liver transplantation: pushing beyond Milan

The Milan criteria have been considered the gold standard for the selection of patients with hepatocellular cancer (HCC) for liver transplantation. However, there is growing evidence that tumor burden is just one of many factors that predict HCC recurrence after liver transplantation.

Modest expansion beyond Milan criteria, including the University of California, San Francisco and up-to-7 criteria, appear to yield acceptable posttransplantation outcomes, but their implementation should achieve a minimal survival threshold to not harm non-HCC patients awaiting liver transplantation. Down-staging of HCC patients into Milan criteria appears to produce excellent posttransplant outcomes similar to those always within Milan criteria. Incorporating α-fetoprotein into the selection scheme may further improve posttransplant outcome. Response to local regional therapy (LRT) may help identify candidates who would do well after liver transplantation even if their initial tumor burden exceeds Milan criteria. Conversely, tumor progression despite LRT is a poor prognostic factor for tumors within or beyond Milan criteria. Under the 'ablate and wait' principle, a sufficient length of time to observe tumor behavior is essential to avoid transplanting those with aggressive tumors too quickly, as these patients would likely do poorly after liver transplantation.

Tumor size and number tell only a partial tale of the characteristics that predict posttransplant outcomes. To this end, successful down-staging appears to carry equivalent posttransplantation outcomes to those always within Milan criteria. Accounting for tumor biology with α-fetoprotein and response to LRT as well as assessing modifiable risk factors such as wait time is crucial to improve selection criteria and improve posttransplantation outcomes.