Downstaging of hepatocellular carcinoma before liver transplantation: Results from a national multicenter prospective cohort study
Edison Xu, Parissa Tabrizian, Julio R. Gutiérrez, Maarouf Hoteit, Tahereh Ghaziani, Kali Zhou, Neehar D. Parikh, Veeral Ajmera, Elizabeth S. Aby, Amy Shui, Rebecca Marino, Allison Martin, Christopher Wong, Karissa Kao, Shravan Dave, Sander Florman, Francis Y. Yao, Neil Mehta
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.