A Prospective Multicenter Validation of RETREAT for Post-Transplantation Hepatocellular Carcinoma Recurrence Prediction

Background: The RETREAT score is a simple risk stratification tool for post-liver transplantation (LT) hepatocellular carcinoma (HCC) recurrence that has been validated in retrospective cohort studies. A prospective, multicenter study is needed to further demonstrate accuracy especially given evolving clinical demographics and HCC transplant practice. Aim: To validate and compare the RETREAT score to other post-LT HCC recurrence risk scores in a contemporary, prospective cohort of patients Approach: We prospectively enrolled post-LT HCC patients from 8 centers between 2018 and 2022. The primary outcome was post-LT recurrence-free survival (RFS). Secondary outcomes included post-LT and post-recurrence survival. Model performance, determined using concordance index, Akaike information criterion, integrated Brier score, and calibration, was compared to that of other established risk scores. Results: We included 1166 post-LT HCC patients of which 78 (6.7%) had post-LT HCC recurrence after a median follow up time of 2.2 years (IQR 1.2 – 3.2). Median RETREAT score was 4 (IQR 3 – 5) in patients with post-LT HCC recurrence and 1 (IQR 1 – 2) in patients without. Those with a RETREAT score of 0, 3, and 5+ had a 99.4%, 84.1%, and 55.6% RFS, respectively, at 3 years post-LT. The RETREAT score was also able to stratify post-LT overall and post-recurrence survival. The RETREAT score’s concordance index was 0.81 (95% CI: 0.77 – 0.85) and outperformed the MORAL and RELAPSE scores across multiple metrics. Conclusion: The RETREAT score retains high accuracy for predicting post-LT HCC recurrence, further supporting RETREAT guided post-LT HCC surveillance and care.