Prediction of Hepatocellular Carcinoma Recurrence beyond Milan Criteria after Resection

Jian Zheng, Joanne F. Chou, Mithat Gönen, Neeta Vachharajani, William C. Chapman, Maria B. Majella Doyle, Simon Turcotte, Franck Vandenbroucke-Menu, Réal Lapointe, Stefan Buettner, Bas Groot Koerkamp, Jan N.M. Ijzermans, Chung Yip Chan, Brian K.P. Goh, Jin Yao Teo, Juinn Huar Kam, Prema R. Jeyaraj, Peng Chung Cheow, Alexander Y.F. Chung, Pierce K.H. ChowLondon L.P.J. Ooi, Vinod P. Balachandran, T. Peter Kingham, Peter J. Allen, Michael I. D'Angelica, Ronald P. Dematteo, William R. Jarnagin, Ser Yee Lee

Research output: Contribution to journalArticlepeer-review

61 Scopus citations


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.

Original languageEnglish
Pages (from-to)693-701
Number of pages9
JournalAnnals of surgery
Issue number4
StatePublished - Oct 1 2017


  • Milan criteria
  • clinical risk score
  • hepatocellular carcinoma
  • recurrence pattern
  • resection
  • transplant


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