Downstaging of hepatocellular carcinoma before liver transplantation: Results from a national multicenter prospective cohort study

Abstract

Background and aims: Patients with HCC meeting United Network for Organ Sharing (UNOS)-downstaging (DS) criteria have excellent post-liver transplantation (LT) outcomes. Studies on HCC beyond UNOS-DS criteria ("All-Comers" [AC]) have been limited by small sample size and short follow-up time, prompting this analysis.

Approach and results: Three hundred twenty-six patients meeting UNOS-DS and 190 meeting AC criteria from 9 LT centers across 5 UNOS regions were enrolled from 2015 to 2023 and prospectively followed. Competing risk analysis and Kaplan-Meier method were used to evaluate DS and LT outcomes, and Fine-and-Gray and Cox models were used to identify predictors of outcomes. AC and UNOS-DS had similar median alpha-fetoprotein (15 vs. 12 ng/mL; p =0.08), MELD (9 vs. 9; p =0.52), and Child-Pugh (A vs. A; p =0.30). Two years after the first local regional therapy, 82% of UNOS-DS and 66% of AC were successfully downstaged ( p <0.001). In AC, DS rates were 72% for tumor number plus diameter of largest lesion <10, 51% for sum 10-12, and 39% for sum >12 ( p =0.01). Yttrium-90 achieved higher DS success than transarterial chemoembolization in AC (74% vs. 65%; p <0.001). 48% of UNOS-DS and 40% of AC underwent LT ( p =0.10). Five-year post-LT survival was similar between UNOS-DS and AC (74% vs. 72%; p =0.77), although 5-year post-LT recurrence was higher in AC (30% vs. 14%; p =0.02).

Conclusions: Despite higher HCC recurrence and lower intention-to-treat survival in AC, post-LT survival was comparable between UNOS-DS and AC. Yttrium-90 attained higher DS success than transarterial chemoembolization in AC. LT after DS is feasible in AC, though defining an upper limit in tumor burden may be necessary.

Keywords: hepatocellular carcinoma; liver transplantation; local regional therapy; recurrence; survival.