Mehta N, Frenette C, Tabrizian P, et al. - Since the United Network of Organ Sharing (UNOS) adopted uniform criteria for down-staging (UNOS-DS) of hepatocellular carcinoma (HCC) prior to liver transplantation (LT), researchers desired to know about the down-staging success rate and intention-to-treat outcomes across broad geographic regions in this analysis. From 2016 to 2019, consecutive patients with HCC undergoing down-staging based on UNOS-DS criteria were prospectively evaluated (n = 209) in this first multi-regional study (7 centers, 4 UNOS regions). The chance of successful down-staging to Milan criteria and dropout at 2 years from the initial down-staging procedure was 87.7% and 37.3%, respectively. In this first prospective multi-regional study based on UNOS-DS criteria, the authors found a successful down-staging rate of > 80% and comparable efficacy of chemoembolization and Y-90 radioembolization as initial down-staging treatment. Despite a 95% 2-year post-LT survival rate, a high rate of tumor under-staging was observed. Additional local regional therapy to lessen viable tumor burden may help to reduce tumor under-staging.