Downstaging Outcomes for Hepatocellular Carcinoma: Results From the Multicenter Evaluation of Reduction in Tumor Size before Liver Transplantation (MERITS-LT) Consortium

Gastroenterology. 2021 Nov;161(5):1502-1512. doi: 10.1053/j.gastro.2021.07.033. Epub 2021 Jul 28.

Abstract

Background & aims: United Network of Organ Sharing (UNOS) has adopted uniform criteria for downstaging (UNOS-DS) of hepatocellular carcinoma (HCC) before liver transplantation (LT), but the downstaging success rate and intention-to-treat outcomes across broad geographic regions are unknown.

Methods: In this first multiregional study (7 centers, 4 UNOS regions), 209 consecutive patients with HCC undergoing downstaging based on UNOS-DS criteria were prospectively evaluated from 2016 to 2019.

Results: Probability of successful downstaging to Milan criteria and dropout at 2 years from the initial downstaging procedure was 87.7% and 37.3%, respectively. Pretreatment with lectin-reactive α-fetoprotein ≥10% (hazard ratio, 3.7; P = .02) was associated with increased dropout risk. When chemoembolization (n = 132) and yttrium-90 radioembolization (n = 62) were compared as the initial downstaging treatment, there were no differences in Modified Response Evaluation Criteria In Solid Tumors response, probability of or time to successful downstaging, waiting list dropout, or LT. Probability of LT at 3 years was 46.6% after a median of 17.2 months. In the explant, 17.5% had vascular invasion, and 42.8% exceeded Milan criteria (understaging). The only factor associated with understaging was the sum of the number of lesions plus largest tumor diameter on the last pre-LT imaging, and the odds of understaging increased by 35% per 1-unit increase in this sum. Post-LT survival at 2 years was 95%, and HCC recurrence occurred in 7.9%.

Conclusion: In this first prospective multiregional study based on UNOS-DS criteria, we observed a successful downstaging rate of >80% and similar efficacy of chemoembolization and yttrium-90 radioembolization as the initial downstaging treatment. A high rate of tumor understaging was observed despite excellent 2-year post-LT survival of 95%. Additional LRT to reduce viable tumor burden may reduce tumor understaging.

Keywords: Local Regional Therapy (LRT); Tumor Recurrence; Waiting List Dropout; α-Fetoprotein (AFP).

Publication types

  • Multicenter Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Aged
  • Carcinoma, Hepatocellular / diagnostic imaging
  • Carcinoma, Hepatocellular / mortality
  • Carcinoma, Hepatocellular / pathology
  • Carcinoma, Hepatocellular / therapy*
  • Chemoembolization, Therapeutic* / adverse effects
  • Chemoembolization, Therapeutic* / mortality
  • Disease Progression
  • Feasibility Studies
  • Female
  • Humans
  • Liver Neoplasms / diagnostic imaging
  • Liver Neoplasms / mortality
  • Liver Neoplasms / pathology
  • Liver Neoplasms / therapy*
  • Liver Transplantation* / adverse effects
  • Liver Transplantation* / mortality
  • Male
  • Middle Aged
  • Neoplasm Recurrence, Local
  • Neoplasm Staging
  • Patient Dropouts
  • Prospective Studies
  • Radiopharmaceuticals / adverse effects
  • Radiopharmaceuticals / therapeutic use*
  • Risk Assessment
  • Risk Factors
  • Time Factors
  • Treatment Outcome
  • Tumor Burden
  • United States
  • Waiting Lists* / mortality

Substances

  • Radiopharmaceuticals