Pretreatment Prior to Transplantation
Despite the improved prioritization for HCC under the MELD-based allocation system, there has been an increasing demand of a relatively fixed supply of deceased donor organs. This, in turn, has led to an increased dropout rate from the waitlist and worse overall survival of HCC patients awaiting transplantation. Llovet et al documented a 25% dropout rate in the first 6-months awaiting liver transplantation. In an analysis of the UNOS/Organ Procurement and Transplantation Network (OPTN) database, Pelletier et al demonstrated a 12% 1-year and 20% 3-year risk of dropping off the waitlist due to tumor progression or death. The impact of pretransplant therapy in this study is unknown, but it does highlight the significant risk of waitlist drop-out and regional variation in transplant rates for HCC. In an effort to slow or halt disease progression while on the waitlist, many centers began to utilize ablative therapy such as trans-arterial chemoembolization (TACE), radiofrequency ablation (RFA), or percutaneous ethanol injection (PEI). Utilizing pretransplant chemoembolization, Maddala et al at the Mayo Clinic demonstrated 15% 6-month and 25% 1-year waitlist dropout rates. Mazzaferro et al treated 60 tumors in 50 patients with pretransplant RFA. After a median waiting time of 9.5 months, there were no patients dropped due to tumor progression and the 1- and 3-year overall survival rates were 95% and 83%, respectively.
Although pretransplant locoregional therapy such as TACE has a well-defined role as a "bridge" to transplant,[60,61,62] its role as neoadjuvant therapy to provide oncologic benefit after transplantation is less clear. In a retrospective analysis from two centers, Yao and colleagues demonstrated a beneficial effect of locoregional therapy in posttransplant recurrence-free survival for patients with T2 and T3 HCC. In these patients, the 5-year recurrence-free survival rate was 93.8% for patients who received locoregional therapy versus 80.6% for those did not undergo pretransplant treatment (p = 0.049). The treatment benefit was most notable in those patients with T3 tumors suggesting that preoperative therapy may add a survival benefit to those who undergo transplantation, but may also allow for selection of patients whose tumors have "good biology." Another report by Bharat retrospectively evaluated 100 patients with HCC who underwent transplantation with 46 receiving pretransplant locoregional therapy. Those who underwent pretransplant therapy had better 5-year survival rates (82.4% vs. 51.8%;p = 0.01). When stratified by tumor stage, the treatment benefit was seen only in those with T2-T4 tumors. Patients with T1 tumors experienced excellent outcomes with or without neoadjuvant locoregional therapy. Interestingly, 16 patients were found to have 100% tumor necrosis on pathologic evaluation of the explanted liver. Eleven of these 16 had T2 or T3 disease and experienced better survival than those with T1 tumors as determined by pretransplant radiographic study.
Semin Liver Dis. 2013;33(3):282-292. © 2013 Thieme Medical Publishers