06/30/2026  |  Clínic Barcelona

https://www.clinicbarcelona.org/en/news/an-international-consensus-article-establishes-clinical-trial-design-in-liver-cancer 

Researchers from the Cancer Area at IDIBAPS and the Clínic Barcelona Comprehensive Cancer Centre have led the development of an international consensus document published in Nature Reviews Clinical Oncology, one of the most prestigious journals in oncology.

The article, promoted by the four main scientific societies in liver oncology —the European Association for the Study of the Liver (EASL), the American Association for the Study of Liver Diseases (AASLD), the International Liver Cancer Association (ILCA) and the American Society of Clinical Oncology (ASCO)— provides 102 consensus recommendations to guide clinical trial design and the definition of endpoints in phase II and III experimental studies in hepatocellular carcinoma.

This initiative has been led by Dr Josep M. Llovet, Head of the Translational Research in Hepatic Oncology group at IDIBAPS, Professor of Medicine at the University of Barcelona, ICREA professor, and Professor of Medicine at the Icahn School of Medicine at Mount Sinai; with the participation of Dr Ezequiel Mauro, a member of the same group.

What is hepatocellular carcinoma?
Hepatocellular carcinoma is the most common type of liver cancer, affecting close to one million new patients annually. It typically develops in the context of chronic liver disease, such as cirrhosis or viral hepatitis. This coexistence of tumor and underlying liver damage makes disease progression particularly complex and has a direct impact on both prognosis and treatment options.

In recent years, treatment has evolved significantly, and nine systemic therapies are now available. While this has expanded treatment options for patients, it has also made the design of clinical trials more challenging.

Towards a redefinition of clinical trial design
The article provides a comprehensive analysis of how clinical trials in hepatocellular carcinoma have traditionally been designed and identifies key methodological limitations that hinder the comparison of results across studies, while proposing new strategies to overcome them.

The authors define trial design across five specific areas: screening, treatment in early, intermediate and advanced stages, and clinical trials in the liver transplantation setting. They provide 102 recommendations that achieved consensus through a voting system among panelists from the four scientific societies. For each scenario, the target population, primary endpoints, recommended control arms, stratification factors and expected clinical benefit are defined.

The consensus document also sets out recommendations for biomarker-driven studies, the incorporation of quality-of-life parameters, patient perspective and diversity, as well as regulatory requirements for drug approval.

Challenges in evaluating outcomes in liver cancer
One of the central aspects of the consensus article is the definition of clinical trial endpoints, which are used to assess treatment efficacy. In hepatocellular carcinoma, this is particularly challenging because outcomes may be influenced both by tumor progression and by the underlying liver disease. Therefore, selecting appropriate endpoints is essential for accurately interpreting the benefits of new treatments.

The article reviews the advantages and limitations of the main endpoints currently used, such as overall survival, recurrence-free survival and progression-free survival, and provides recommendations on how to adapt them to the evolving therapeutic landscape in each clinical setting.

A major contribution to international research
This consensus document establishes a shared framework for leading scientific societies in hepatology and oncology, aimed at improving the design of future clinical trials in liver cancer and facilitating the generation of more robust, comparable and clinically meaningful results.

The participation of researchers from the Cancer Area at IDIBAPS and the Clínic Barcelona Comprehensive Cancer Centre (4CB) reinforces the role of the Clínic Campus as an international reference in hepatocellular carcinoma research and in the development of new strategies to optimize treatment evaluation.

Article reference:

Llovet, J.M., Mauro, E., Rimassa, L. et al. Trial design and end points in hepatocellular carcinoma: an EASL–AASLD–ILCA consensus statement. Nat Rev Clin Oncol (2026). https://doi.org/10.1038/s41571-026-01160-z