Prediction of Hepatocellular Carcinoma Recurrence Beyond Milan Criteria After Resection: Validation of a Clinical Risk Score in an International Cohort.

Abstract

This study aims to validate a previously reported recurrence clinical risk score (CRS). Salvage transplantation after hepatocellular carcinoma (HCC) resection is limited to patients who recur within Milan criteria (MC). Predicting recurrence patterns may guide treatment recommendations. An international, multicenter cohort of R0 resected HCC patients were categorized by MC status at presentation. CRS was calculated by assigning 1 point each for initial disease beyond MC, multinodularity, and microvascular invasion. Recurrence incidences were estimated using competing risks methodology, and conditional recurrence probabilities were estimated using the Bayes theorem. From 1992 to 2015, 1023 patients were identified, of whom 613 (60%) recurred at a median follow-up of 50 months. CRS was well validated in that all 3 factors remained independent predictors of recurrence beyond MC (hazard ratio 1.5-2.1, all P < 0.001) and accurately stratified recurrence risk beyond MC, ranging from 19% (CRS 0) to 67% (CRS 3) at 5 years. Among patients with CRS 0, no other factors were significantly associated with recurrence beyond MC. The majority recurred within 2 years. After 2 years of recurrence-free survival, the cumulative risk of recurrence beyond MC within the next 5 years for all patients was 14%. This risk was 12% for patients with initial disease within MC and 17% for patients with initial disease beyond MC. CRS accurately predicted HCC recurrence beyond MC in this international validation. Although the risk of recurrence beyond MC decreased over time, it never reached zero.