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

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Abstract

Objective:

This study aims to validate a previously reported recurrence clinical risk score (CRS).

Summary of Background Data:

Salvage transplantation after hepatocellular carcinoma (HCC) resection is limited to patients who recur within Milan criteria (MC). Predicting recurrence patterns may guide treatment recommendations.

Methods:

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.

Results:

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.

Conclusions:

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.

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