Liver transplantation for hepatocellular carcinoma: Are the Milan criteria still valid?

Liver transplantation (LT) offers excellent results for candidates with hepatocellular carcinoma (HCC) selected according to the Milan criteria. A selection strategy exclusively based on the Milan criteria, however, maintains a dangerous risk of prognostic inaccuracy due to the intrinsic diagnostic limitations of imaging procedures and to the surrogate nature of size and number of tumors with respect to more direct markers of biological aggressiveness like tumor grade, and vascular invasion. Moreover, the use of Milan criteria as dropout criteria seems to overestimate the risk of tumor biological progression before LT.The basis for allocation of donor liver to patients with HCC will undoubtedly evolve over coming years beyond the simple across-the-board application of Milan criteria taking into account the following key concepts: (1) a reliable prognostic staging system for HCC will help to optimize allocation of the various therapeutic alternatives to HCC patients; (2) new molecular biomarkers may improve the prognostic accuracy of selection criteria for LT; (3) aggressive multimodality neoadjuvant therapy can downstage HCC and limit tumor progression before LT, and treatment response may inform about tumor biology; and (4) Prioritization of HCC patients for LT should take into account not only tumor characteristics, but also response to neoadjuvant therapy, time on the waiting list, and the suitability of alternative donor sources including split/living donor LT, and marginal livers.