National Experience on Down‐Staging of Hepatocellular Carcinoma Before Liver Transplant: Influence of Tumor Burden, Alpha‐Fetoprotein, and Wait Time

• Published in: Hepatology (Baltimore, Md.) Vol. 71; no. 3; pp. 943 - 954
• Main Authors: Mehta, Neil, Dodge, Jennifer L., Grab, Joshua D., Yao, Francis Y.
• Format: Journal Article
• Language: English
• Published: United States Wiley Subscription Services, Inc 01.03.2020
• Subjects: Aged; alpha-Fetoproteins - analysis; Carcinoma, Hepatocellular - blood; Carcinoma, Hepatocellular - mortality; Carcinoma, Hepatocellular - pathology; Carcinoma, Hepatocellular - surgery; Female; Hepatocellular carcinoma; Hepatology; Humans; Liver cancer; Liver Neoplasms - blood; Liver Neoplasms - mortality; Liver Neoplasms - pathology; Liver Neoplasms - surgery; Liver Transplantation; Liver transplants; Male; Middle Aged; Neoplasm Recurrence, Local - epidemiology; Neoplasm Staging; Retrospective Studies; Survival; Transplants & implants; Tumor Burden; Waiting Lists
• ISSN: 0270-9139; 1527-3350
• DOI: 10.1002/hep.30879

Background and Aims United Network for Organ Sharing (UNOS) recently implemented a national policy granting priority listing for liver transplantation (LT) in patients who achieved down‐staging of hepatocellular carcinoma (HCC) to Milan criteria. We aimed to evaluate the national experience on down‐staging by comparing two down‐staging groups with (1) tumor burden meeting UNOS down‐staging (UNOS‐DS) inclusion criteria and (2) “all‐comers” (AC‐DS) with initial tumor burden beyond UNOS‐DS criteria versus patients always within Milan. Approach and Results This is a retrospective analysis of the UNOS database of 3,819 patients who underwent LT from 2012 to 2015, classified as always within Milan (n = 3,276), UNOS‐DS (n = 422), and AC‐DS (n = 121). Median time to LT was 12.8 months in long wait regions, 6.5 months in mid wait regions (MWR), and 2.6 months in short wait regions (SWR). On explant, vascular invasion was found in 23.7% of AC‐DS versus 16.9% of UNOS‐DS and 14.4% of Milan (P = 0.002). Kaplan‐Meier 3‐year post‐LT survival was 83.2% for Milan, 79.1% for UNOS‐DS (P = 0.17 vs. Milan), and 71.4% for AC‐DS (P = 0.04 vs. Milan). Within down‐staging groups, risk of post‐LT death in multivariable analysis was increased in SWR or MWR (hazard ratio [HR], 3.1; P = 0.005) and with alpha‐fetoprotein (AFP) ≥ 100 ng/mL at LT (HR, 2.4; P = 0.009). The 3‐year HCC recurrence probability was 6.9% for Milan, 12.8% for UNOS‐DS, and 16.7% for AC‐DS (P < 0.001). In down‐staging groups, AFP ≥ 100 (HR, 2.6; P = 0.02) was the only independent predictor of HCC recurrence. Conclusions Our results validated UNOS‐DS criteria based on comparable 3‐year survival between UNOS‐DS and Milan groups. Additional refinements based on AFP and wait time may further improve post‐LT outcomes in down‐staging groups, especially given that reported 3‐year recurrence was higher than in those always within Milan criteria.