The Real Impact of Bridging or Downstaging on Survival Outcomes after Liver Transplantation for Hepatocellular Carcinoma

Abstract

<b><i>Introduction:</i></b> There is no consensus regarding selection criteria on liver transplantation (LT) for hepatocellular carcinoma (HCC), especially for living donor liver transplantation, although emerging evidence has been found for the effectiveness of bridging or downstaging. <b><i>Objective:</i></b> We evaluated the long-term outcomes of patients who underwent LT with or without bridging or downstaging for HCC. <b><i>Methods:</i></b> This retrospective study included 896 LT recipients with HCC between June 2005 and May 2015. Recurrence-free survival (RFS), overall survival (OS), and their associated factors were evaluated. <b><i>Results:</i></b> The 5-year RFS in the full cohort of 896 patients was 82.4%, and the OS was 85.3%. In patients with initial Organ Procurement and Transplantation Network (OPTN) T1 and T2, the 5-year RFS and OS did not significantly differ between LT groups with and without bridging (all <i>p</i> ≥ 0.05). The 5-year RFS and OS of OPTN T3 patients with successful downstaging were not significantly different from those of patients with OPTN T2 with primary LT (<i>p</i> = 0.070 and <i>p</i> = 0.185), but were significantly higher than in patients with OPTN T3 with downstaging failure and initial OPTN T1 or T2 with progression (all <i>p</i> &#x3c; 0.001). In the multivariate analysis, last alpha-fetoprotein before LT ≥70 ng/mL (hazard ratio [HR]: 1.77, <i>p</i> = 0.001; HR: 1.72, <i>p</i> = 0.004), pretransplant HCC status exceeding the Milan criteria (HR: 5.12, <i>p</i> &#x3c; 0.001; HR: 3.31, <i>p</i> &#x3c; 0.001), and positron emission tomography positivity (HR: 2.57, <i>p</i> &#x3c; 0.001; HR: 2.57, <i>p</i> &#x3c; 0.001) were independent predictors for worse RFS and OS. <b><i>Conclusions:</i></b> The impact of bridging therapy on survival outcomes is limited in patients with early-stage HCC, whereas OPTN T1 or T2 with progression provides worse prognosis. OPTN T3 should undergo LT after successful downstaging, and OPTN T3 with successful downstaging allows for acceptable long-term posttransplant outcomes.