Long-term Effects Of Pre-transplant Downstaging On Recipients With Hepatocellular Carcinoma

Background:China has the highest incidence of hepatocellular carcinoma (HCC) in the world due to hepatitis B virus (HBV) infection. Liver transplantation is the most effective treatment of choice for HCC to date. Downstaging is one of the most hot topics in the context of liver transplantation for recipients with HCC, which can control tumor load while recipients are waiting for the liver graft. Great progress has been made in this field under the collaboration of liver transplant centers around the world. Yet, there are still many controversies. An international consensus conference held in2010in Zurich, Switzerland presented5key statements in downstaing for recipients with HCC. The current study aims to analyze the long-term influence of downstaging on liver transplant recipients with HCC, and the different effects that might exit in different modalities of downstaging treatments.Methods:We retrospectively analyzed data of101HCC recipients who received pre-transplant downstaging in Liver Transplantation Center, the First Affiliated Hospital of Zhejiang University (Downstaging group). Another101HCC recipients without pre-transplant downstaging therapies during the same period were yielded as the comparison group (Non-downstaging group). We also split the Downstaging group into4subgroups according to different types of downstaging:1) TACE group, N=65;2) RFA group, N=9;3) TACE+RFA group, N=20;4) Others, N=7. Kaplan-Meier method was used to analyze the overall and tumor-free survival rates. And we used COX regression model to analyze the predictors of overall and tumor-free survival.Results:Patients in the Downstaging group versus Non-do wnstaging group had similar baseline characteristics. At a median follow-up time of15months (inter-quartile7.00months-33.75months),22recipients died in the Downstaging group, and40died in the Non-downstaging group. Thirty-two recipients and51recipients suffered from tumor recurrence in Downstaging and Non-downstaging group, respectively. The1year,3year, and5year overall survival in Downstaging group was84.7%,67.8%and64.4%. significantly superior than that in Non-downstaging group, with71.8%,53.5%and51.5%at the same time interval (P=0.04). The1year,3year, and5year tumor-free survival was66.7%,58.6%and58.6%in Downstaging group and,54.6%,43.4%and43.4%in Non-downstaging group (P=0.016). Cox regression analysis identified macrovascular invasion (hazard ratio (HR)2.47,95%confidence interval (CI)1.30-4.68, P=0.006), diameter of largest tumor (HR2.96,95%Cl1.56-5.59, P=0.001) and number of tumor nodules (HR5.23,95%CI2.70-10.14, P<0.001) were predictors of overall survival. And diameter of largest tumor (HR2.00,95%CI1.01-3.99, P=0.048), number of tumor nodules (HR2.08,95%CI1.06-4.08, P=0.033), alpha-fetoprotein (AFP)(HR2.42,95%CI1.43-4.09. P=0.001), macrovascular invasion (HR1.80,95%CI1.03-3.14, P=0.04) and downstaging treatment (HR0.59,95%CI0.35-1.00, P=0.048) were predictors of tumor-free survival. No significant differences existed in the1year,3year (and5year) overall survival and tumor-free survival between different downstaging groups:81.9%,63.3% and58.8%, and61.1%,52.8%and52.8%in TACE group;100%,100%and100%and100%,100%and100%in RFA group;84.0%,84.0%and72.0%,36.0%in TACE+RFA group;60.0%,60.0%and57.1%,57.1%in other group (both P>0.05).Conclusion:Pre-transplant downstaging treatment is a effective way of treatment to improve overall and tumor-free survival in recipient with HCC, and a predictor for tumor-free survival. No differences on long-term survival exist between different downstaging modalities. In the era of graft organ shortage, pre-transplant downstaging could be perceived as a valuable treatment of choice for recipients with HCC.