Reassessing the Boundaries of Liver Transplantation for Hepatocellular Carcinoma: Where Do We Stand With Tumor Down-Staging?

Down-staging of hepatocellular carcinoma prior to liver transplantation (LT) has generated a lot of interest in recent years and has been identified in two recent national conferences on hepatocellular carcinoma as one of the priorities for research. Down-staging is defined as reduction in the tumor burden using local regional therapy specifically to meet acceptable criteria for LT. The rationale behind down-staging of tumors initially exceeding conventional criteria for LT is to select a subgroup of tumors with favorable biology and prognosis for LT as assessed by their response to local regional therapy. The expectation is to achieve comparable posttransplant survival between patients who achieve successful tumor down-staging before LT and those whose tumors meet LT criteria at the outset without needing down-staging. The application of tumor down-staging requires a highly structured approach using a treatment protocol that includes five essential components: eligibility criteria, down-staging endpoints, selection of the type of local regional therapy, minimal observation period from successful tumor down-staging to LT, and criteria for treatment failure and exclusion from LT. This review article summarizes published data on down-staging and addresses key questions related to each of the components of the down-staging protocol as well as treatment efficacy. Conclusion: Based on a review of published data and recommendations from recent national and international conferences on hepatocellular carcinoma and LT, a standardized down-staging protocol is proposed to further evaluate the feasibility and efficacy of applying tumor down-staging on a broader scale.