Liver Transplantation Outcomes in a U.S. Multicenter Cohort of 789 Patients With Hepatocellular Carcinoma Presenting Beyond Milan Criteria

Hepatology. 2020 Dec;72(6):2014-2028. doi: 10.1002/hep.31210.

Abstract

Background and aims: The Organ Procurement and Transplantation Network recently approved liver transplant (LT) prioritization for patients with hepatocellular carcinoma (HCC) beyond Milan Criteria (MC) who are down-staged (DS) with locoregional therapy (LRT). We evaluated post-LT outcomes, predictors of down-staging, and the impact of LRT in patients with beyond-MC HCC from the U.S. Multicenter HCC Transplant Consortium (20 centers, 2002-2013).

Approach and results: Clinicopathologic characteristics, overall survival (OS), recurrence-free survival (RFS), and HCC recurrence (HCC-R) were compared between patients within MC (n = 3,570) and beyond MC (n = 789) who were down-staged (DS, n = 465), treated with LRT and not down-staged (LRT-NoDS, n = 242), or untreated (NoLRT-NoDS, n = 82). Five-year post-LT OS and RFS was higher in MC (71.3% and 68.2%) compared with DS (64.3% and 59.5%) and was lowest in NoDS (n = 324; 60.2% and 53.8%; overall P < 0.001). DS patients had superior RFS (60% vs. 54%, P = 0.043) and lower 5-year HCC-R (18% vs. 32%, P < 0.001) compared with NoDS, with further stratification by maximum radiologic tumor diameter (5-year HCC-R of 15.5% in DS/<5 cm and 39.1% in NoDS/>5 cm, P < 0.001). Multivariate predictors of down-staging included alpha-fetoprotein response to LRT, pathologic tumor number and size, and wait time >12 months. LRT-NoDS had greater HCC-R compared with NoLRT-NoDS (34.1% vs. 26.1%, P < 0.001), even after controlling for clinicopathologic variables (hazard ratio [HR] = 2.33, P < 0.001) and inverse probability of treatment-weighted propensity matching (HR = 1.82, P < 0.001).

Conclusions: In LT recipients with HCC presenting beyond MC, successful down-staging is predicted by wait time, alpha-fetoprotein response to LRT, and tumor burden and results in excellent post-LT outcomes, justifying expansion of LT criteria. In LRT-NoDS patients, higher HCC-R compared with NoLRT-NoDS cannot be explained by clinicopathologic differences, suggesting a potentially aggravating role of LRT in patients with poor tumor biology that warrants further investigation.

Publication types

  • Multicenter Study

MeSH terms

  • Ablation Techniques / methods*
  • Ablation Techniques / statistics & numerical data
  • Carcinoma, Hepatocellular / diagnosis
  • Carcinoma, Hepatocellular / mortality
  • Carcinoma, Hepatocellular / pathology
  • Carcinoma, Hepatocellular / therapy*
  • Disease-Free Survival
  • End Stage Liver Disease / diagnosis
  • End Stage Liver Disease / mortality
  • End Stage Liver Disease / pathology
  • End Stage Liver Disease / therapy*
  • Female
  • Follow-Up Studies
  • Humans
  • Liver / diagnostic imaging
  • Liver / pathology
  • Liver / radiation effects
  • Liver / surgery
  • Liver Neoplasms / diagnosis
  • Liver Neoplasms / mortality
  • Liver Neoplasms / pathology
  • Liver Neoplasms / therapy*
  • Liver Transplantation / standards
  • Liver Transplantation / statistics & numerical data*
  • Male
  • Middle Aged
  • Neoadjuvant Therapy / methods
  • Neoplasm Recurrence, Local / epidemiology*
  • Neoplasm Recurrence, Local / prevention & control
  • Neoplasm Staging
  • Radiotherapy, Adjuvant / methods
  • Radiotherapy, Adjuvant / statistics & numerical data
  • Retrospective Studies
  • Severity of Illness Index
  • Tissue and Organ Procurement / standards
  • Tumor Burden / radiation effects
  • United States / epidemiology
  • Waiting Lists / mortality