Pretransplant recurrent liver cancer prediction score (p-RELAPSE) to risk stratify hepatocellular carcinoma patients undergoing liver transplantation: validation in an international multicenter retrospective cohort

Background: Selection of patients with hepatocellular carcinoma (HCC) for liver transplantation (LT) increasingly integrates dynamic tumor biology alongside morphometric criteria. Methods: We developed and externally validated the pre-transplant REcurrent Liver cAncer Prediction ScorE (p-RELAPSE) to predict post-LT recurrence using two retrospective cohorts. Post-LT outcomes of 4420 HCC patients undergoing LT in the US Multicenter HCC Transplant Consortium (UMHTC) were analyzed to derive p-RELAPSE using a competing risks multivariable model, with external validation in 1736 HCC LT recipients from the European Hepatocellular Cancer Liver Transplant (EurHeCaLT) group. Results: The UMHTC training ( n = 2893), internal validation ( n = 1527), and EurHeCaLT ( n = 1736) cohorts showed comparable 5-year overall survival (69.4–71.0%), recurrence-free survival (66.2–66.3%), and recurrence incidence (12.6–14.4%; all P > 0.05). p-RELAPSE incorporated Milan criteria (MC) status, downstaging, maximum tumor diameter, dynamic alpha-fetoprotein (AFP) response, and waitlist time. The model stratified recurrence risk even within MC patients. In EurHeCaLT, p-RELAPSE achieved a C-statistic of 0.69, outperforming MC, French AFP, Up-to-7, pre-MORAL, and New York/California models ( P < 0.05). Conclusions: By integrating AFP dynamics and waitlist time, p-RELAPSE refines post-LT recurrence risk stratification, identifying MC patients unlikely to benefit from LT and non-MC patients with favorable outcomes. This externally validated model provides a robust framework for individualized pre-LT decision-making in HCC candidates.

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Journal
International Journal of Surgery
Published
2026-11-11
DOI
https://doi.org/10.1097/js9.0000000000005714
Primary Topic
Hepatocellular Carcinoma Treatment and Prognosis
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article
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article

Pretransplant recurrent liver cancer prediction score (p-RELAPSE) to risk stratify hepatocellular carcinoma patients undergoing liver transplantation: validation in an international multicenter retrospective cohort

Sander S Florman, Vatche Garen Agopian, Maria Hoppe‐Lotichius, Olga Ciccarelli et al.
International Journal of Surgery
Hepatocellular Carcinoma Treatment and Prognosis
article

Pretransplant recurrent liver cancer prediction score (p-RELAPSE) to risk stratify hepatocellular carcinoma patients undergoing liver transplantation: validation in an international multicenter retrospective cohort

Sander S Florman, Vatche Garen Agopian, Maria Hoppe‐Lotichius, Olga Ciccarelli, Trevor L. Nydam, Maarouf A. Hoteit, Johnny C. Hong, C. Burcin Taner, Christopher M. Jones, Umberto Cillo, Richard M. Ruiz, Marco Vivarelli, Parissa Tabrizian, Alan N. Langnas, Gabriel T. Schnickel, Karim Jarir Halazun, Carol A. Carney, Mindie H. Nguyen, Elizabeth C. Verna, Tommaso Maria Manzia, Andrew S. Barbas, Constance M. Mobley, Thomas Fishbein, Ricardo Henao, Abhinav Humar, Hamed Zaribafzadeh, Göran B. Klintmalm, Daniela Markovic, Dominic Amara, Amit D. Tevar, Neeta A. Vachharajani, James F. Markmann, Massimo Rossi, Abbas A. Rana, William C. Chapman, Marc L. Melcher, Alessandro Vitale, Quirino Lai, Jan Paul Lerut, Jennifer A. Berumen, Andrew Melehy, Benedikt Schaefer, Salvatore Agnes, Benjamin V. Tran, Dimitrios P Moris, Emmanuel A. Tsochatzis, Federico Aucejo, Guiseppe M. Ettorre, Mark Ghobrial, David D. Lee, Debra L. Sudan
article en

Abstract

Background: Selection of patients with hepatocellular carcinoma (HCC) for liver transplantation (LT) increasingly integrates dynamic tumor biology alongside morphometric criteria. Methods: We developed and externally validated the pre-transplant REcurrent Liver cAncer Prediction ScorE (p-RELAPSE) to predict post-LT recurrence using two retrospective cohorts. Post-LT outcomes of 4420 HCC patients undergoing LT in the US Multicenter HCC Transplant Consortium (UMHTC) were analyzed to derive p-RELAPSE using a competing risks multivariable model, with external validation in 1736 HCC LT recipients from the European Hepatocellular Cancer Liver Transplant (EurHeCaLT) group. Results: The UMHTC training ( n = 2893), internal validation ( n = 1527), and EurHeCaLT ( n = 1736) cohorts showed comparable 5-year overall survival (69.4–71.0%), recurrence-free survival (66.2–66.3%), and recurrence incidence (12.6–14.4%; all P > 0.05). p-RELAPSE incorporated Milan criteria (MC) status, downstaging, maximum tumor diameter, dynamic alpha-fetoprotein (AFP) response, and waitlist time. The model stratified recurrence risk even within MC patients. In EurHeCaLT, p-RELAPSE achieved a C-statistic of 0.69, outperforming MC, French AFP, Up-to-7, pre-MORAL, and New York/California models ( P < 0.05). Conclusions: By integrating AFP dynamics and waitlist time, p-RELAPSE refines post-LT recurrence risk stratification, identifying MC patients unlikely to benefit from LT and non-MC patients with favorable outcomes. This externally validated model provides a robust framework for individualized pre-LT decision-making in HCC candidates.

International Journal of Surgery
University of Rome Tor Vergata (IT), Marche Polytechnic University (IT), Houston Methodist (US), Pennsylvania State University (US), Beth Israel Deaconess Medical Center (US), Cleveland Clinic (US), Mount Sinai Hospital (US), NewYork–Presbyterian Hospital (US), Harvard University (US), University of Padua (IT), University of Louisville (US), Innsbruck Medical University (AT), University of California, Los Angeles (US), Duke University (US), Baylor College of Medicine (US), Georgetown University (US), Universität Innsbruck (AT), Washington University in St. Louis (US), Policlinico Umberto I (IT), The Royal Free Hospital (GB), Baylor University Medical Center (US), Agostino Gemelli University Polyclinic (IT), University of California San Diego (US), NYU Langone Health (US), Massachusetts General Hospital (US), University Medical Center of the Johannes Gutenberg University Mainz (DE), Azienda Ospedaliera San Camillo-Forlanini (IT), Duke Medical Center (US), University of Pittsburgh Medical Center (US), Mayo Clinic in Florida (US), Istituti di Ricovero e Cura a Carattere Scientifico (IT), University College London (GB), University of Colorado Anschutz Medical Campus (US), New York University (US), University of Nebraska Medical Center (US), Columbia University (US), University of Pennsylvania (US), Penn State Milton S. Hershey Medical Center (US), Sapienza University of Rome (IT), University of Colorado Denver (US), UCLouvain (BE), Stanford University (US)
Hepatocellular Carcinoma Treatment and Prognosis
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