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.

Figure 1.. Study population.

HCC, hepatocellular carcinoma; LT, liver transplant; UNOS-DS, United Network of Organ Sharing-Downstaging

Figure 2.. 2-year probability of successful downstaging.

(A) Probability of successful downstaging in the UNOS-DS and AC cohorts. (B) Probability of successful downstaging in the AC cohort stratified by the composite variable of number of lesions plus diameter of largest lesion. (C) Probability of successful downstaging in the UNOS-DS and AC cohorts stratified by Y-90 and TACE as first local regional therapy. AC, All-Comers; TACE, transarterial chemoembolization; UNOS-DS, United Network of Organ Sharing-Downstaging

Figure 3.. 5-year intention-to-treat (ITT) survival after first local regional therapy.

(A) ITT survival in the UNOS-DS and AC cohorts. (B) ITT survival in the AC cohort stratified by those who were successfully downstaged and those were not. (C) ITT survival in the UNOS-DS and AC cohorts stratified by Y-90 and TACE as first local regional therapy. AC, All-Comers; ITT, intention-to-treatl; TACE, transarterial chemoembolization; UNOS-DS, United Network of Organ Sharing-Downstaging

Figure 4.. Post-liver transplantation (LT) outcomes.

(A) 5-year post-LT survival in the UNOS-DS and AC cohorts. (B) 5-year post-LT probability of HCC recurrence in the UNOS-DS and AC cohorts. (C) 5-year recurrence-free survival after LT in the UNOS-DS and AC cohorts. AC, All-Comers; HCC, hepatocellular carcinoma; LT, liver transplant UNOS-DS, United Network of Organ Sharing-Downstaging