Clinic Investigation On Downstaging Treatments As A Bridge To Liver Transplantation For Hepatocellular Carcinoma Patients

Objective:This study aimed to analyze the outcomes of loco-regional therapy (LRTs) prior to liver tansplantation (LT) in patients with HCC and further refine the "downstaging protocol".Methods:From June 2006 to October 2010, we analyzed seventy patients: twenty-nine meet the Milan criteria (MC,41.4%), twenty had T3a tumors (28.6%), and twelve had T4a tumors (17.1%), while nine patients were suspected of having tumor vascular invasion (T4b,12.9%). All patients underwent preoperative LRTs. The number of patients, the types of LRTs used before the LT, and their outcomes after the LT were recorded. Survival was calculated by using the Kaplan-Meier method. Univariable and multivariable analyses using the Cox proportional hazards regression model were performed to evaluate the factors associated with the recurrence-free survival.Results:Fourteen patients had necrotic tumors (pTO,20.0%),10 pT1 tumors (14.3%),25 pT2 tumors (35.7%),8 pT3 tumors (11.4%),5 pT4a tumors (7.1%), and 8 pT4b tumors (11.4%). The hispathologic tumors of 23 patients (23/34) beyond MC were downstaged and met the Milan criteria. Underestimated HCCs were present in five HCC patientswho had microvascular invasion. Thirty-four patients had stable HCC bridging to LT and total 13died.The 1-,3-and 4-year overall survival (OS) were 97%,76% and 70%, respectively, with a mean survival time of 27.30±13.74 months. Nine patients died of tumor recurrence. The 1-,3- and 4-year recurrence-free survival rates (RFS) were 92%,73% and 73%, respectively.The 3-year RFS of patients with MC was 89%, which was significantly better than those with pT3 tumors (67%, P=0.018) or pT4 tumors (23%, P=0.000). Although the 3-year RFS of patients with pT3 tumors was also greater than those with pT4 tumors significantly (P=0.040).The 3-year RFS of patients with pathological total tumor diameters (TTD)<7cm was 80%, significantly better than those beyond 7cm (36%, P=0.000). Furthermore the 3-year OS of patients with pathological TTD<7cm was significantly better than those beyond 7cm (64%, P=0.008).The 3-year RFS of patients with AFP level less than 400 ug/L was 85% respectively, significantly better than those beyond 400 ug/L (57%, P=0.024). The 3-year RFS and OS of patients with combination of LRTs were better than mono treatment but no significate difference (P=0.217, P=0.785).Cox proportional hazards model showed that pre-LT AFP level beyond 400 ug/L, pathological TTD beyond 7cm, microvascular invasion, and HCC beyond MC were signifieantly associated with a higher hazard for recurrence.Conclusions:1. The successful downstaging of HCCs can be achieved in carefully selected patients through the use of LRTs. Importantly,these patients undergoing LT may experience a higher RFS.2. "Downstaging protocol" includes patients with HCC beyond MC but without vascular invision and distant metastasis. TACE is eligible for patients with larger hypervascular HCC if liver reserve is good; meanwhile thermal ablation therapies are suited for patients with tumor diameter≤3cm and limited numbers.3. Endpoints of downstaging protocol:HCCs are downstaged to meet MC and AFP level less than 400 ug/L. If no tumor progression observed in a minimum follow-up period of 3 months, these patients may benefit from LT.4. Pre-LT AFP level beyond 400 ug/L, pathological TTD beyond 7cm, microvascular invasion, and HCC beyond MC were associated with a poor survival outcome after downstaging.