Effectiveness of Downstaging Advanced Hepatocellular Carcinoma for Liver Transplantation: Insights from a Decade of Single-Center Experience

Abstract Unresectable patients with hepatocellular carcinoma within UNOS T2 Criteria may go directly to transplantation, but patients with disease burden exceeding T2 must first undergo downstaging treatment prior to multidisciplinary discussion of transplant eligibility. Locoregional therapy is the mainstay of downstaging therapy, which may be used in combination with resection or systemic therapy. A single-center retrospective cohort study was performed, including patients >18 years old with diagnoses of HCC not meeting T2 criteria. Patients were categorized as within the United Network for Organ Sharing Downstaging Criteria (UNOS-DS) or with disease burden beyond UNOS-DS criteria, labeled “all-comers” (AC). Exclusion criteria included mixed HCC/cholangiocarcinoma tumors and metastatic disease. All patients were outside of T2 Criteria—65 DS versus 102 AC. Patient demographics were similar between groups. The DS group was more likely to be downstaged using locoregional therapies (LRT) alone (p < 0.001) and required fewer LRT treatments to achieve downstage. Y90 was the most used LRT, followed by transarterial chemoembolization. Cumulative probability of downstage favored the DS group at all time points (p = 0.004). Overall survival was significantly different between successfully downstaged versus not downstaged patients, regardless of initial disease burden or cohort. Predictors of successful downstaging were the use of LRT and incorporation of resection when appropriate for the AC group. Predictors of poorer outcomes were alfa-fetal-protein ≥ 1,000 and the need for systemic therapy. Waitlisting rates were higher in the DS group (44.6% vs. 24.5%, p = 0.007), but once listed, transplant rates were similar (76% vs. 82%, p = 0.008) as were posttransplant survival (p = 0.250) and recurrence rates (p = 0.232). Our 10-year experience reinforces that a successful downstaging, rather than the initial tumor burden, determines survival in HCC beyond T2 criteria. While patients falling within UNOS-DS criteria achieved more successful downstaging with fewer interventions and made it to transplant more often, a selection of patients within the AC group who had a successful response to downstaging therapies also derived a meaningful benefit when transplanted.