Hepatocellular Carcinoma Outside of the Milan Criteria

Hepatocellular carcinoma (HCC) is a leading cause of cancer deaths worldwide and the incidence and mortality rate are nearly identical in the United States. The Milan Criteria established thresholds of tumor size and number as predictors of optimum overall survival with liver transplant and changed the definitive treatment for HCC. However, after nearly two decades of experience two problems have emerged: post-transplant recurrence continues and an increasing number of patients exceed these size criteria. While tumor burden is an important prognostic factor, it remains limited in its ability to fully define underlying tumor biology and predict recurrence after transplant. Recognizing that tumor size and number are merely surrogate markers of tumor behavior, multiple centers have sought to expand these criteria and consider other oncologic and radiologic factors. Response to locoregional therapies may help to better determine tumor behavior and predict which patients might recur after transplant. Emerging analysis of tumor biology and genetics may also help to predict recurrence more accurately than size alone. Future selection of transplant candidates may be via molecular profiling or chronological imaging changes to identify those patients who would benefit most from the finite number of available grafts, while limiting recurrence after transplant.