Hepatocellular Carcinoma

Resection versus Transplantation

Truman M. Earl; William C. Chapman


Semin Liver Dis. 2013;33(3):282-292. 

In This Article

Expanding the Milan Criteria

Several groups have challenged the restrictions imposed by Milan either through expanding the size criteria or by using liver-directed therapy in an attempt to "downstage" patients with advanced tumors to within criteria.[21,54,64,65,66] Most notable has been the group from UCSF who have proposed criteria of a single tumor ≤6.5cm or up to three tumors, the largest ≤4.5 cm and total tumor diameter ≤8 cm without gross vascular invasion.[21] These numbers were derived from explant tumor characteristics as the authors noted that explant pathology often revealed understaging by preoperative cross-sectional imaging; however, this did not necessarily result in inferior outcome. Of the 168 patients in the initial report, the 5-year recurrence-free survival rate was 90% for the 130 patients with a preoperative tumor stage within Milan versus 94% for the 30 patients that met the UCSF criteria but exceeded Milan (p = 0.58). These criteria were further evaluated in a series of 467 patients who underwent transplantation at UCLA.[54] Based on pretransplant imaging, 173 patients were within Milan criteria, 185 were beyond Milan but within UCSF criteria, and 109 were outside of UCSF criteria. The 5-year patient survival rate was 79% for those meeting Milan versus 64% for those beyond Milan but within UCSF (p = 0.061). Based on explant pathology the survival of those meeting Milan versus meeting only UCSF were 86% versus 81% at 5 years, respectively.

Inherent within the discussion of transplantation for tumors beyond Milan criteria is the idea of tumor downstaging with neoadjuvant locoregional therapy. Majno et al from the hospital Paul Brousse in Paris were the first to apply the concept of tumor downstaging to facilitate transplantation and the practice has been adopted by several centers.[67] A report from Washington University (St. Louis, MO) demonstrated the feasibility of tumor downstaging and the possibility of successful transplantation of advanced tumors using this strategy.[23] Of 202 patients with HCC evaluated for transplantation during the study period, 76 had stage III/IV disease and were otherwise transplant candidates. A median number of two TACE sessions were used and 18 patients (23.7%) achieved adequate downstaging to qualify for transplantation under Milan criteria. Seventeen (22.4%) patients went on to receive a deceased donor allograft at a median of 5.8 ± 3.5 months following their first TACE. The actuarial overall 5-year survival rate for patients with stage 2 disease who were chemoembolized and transplanted was 66% compared with 93.8% in patients with stage 3/4 disease who were downstaged and underwent transplantation (p = 0.03), suggesting that this strategy allows for selection of patients with good prognosis for long-term survival—"favorable biology" tumors. A similar result was seen by the UCSF group who utilized TACE for tumors exceeding Milan, but within UCSF criteria and a minimum observation period of 3 months following tumor therapy.[68] Tumor downstaging was achieved in 43 of 61 patients (70.5%) with treatment failure observed in 18 (29.5%). Of 35 patients who underwent liver transplantation, 13 had complete tumor necrosis, 17 met stage 2 criteria, and five patients were beyond stage 2. One and 4-year overall survival rates following transplantation were 96.2% and 92.1%, respectively. There was no tumor recurrence noted at a median follow-up of 25 months.