Definition of Conversion Therapy and Neoadjuvant Therapy for Hepatocellular Carcinoma: A Consensus Guideline from the Japan Liver Cancer Association

With the advent of novel systemic therapies that provide high response rates, such as lenvatinib, atezolizumab-bevacizumab, durvalumab-tremelimumab, and nivolumab-ipilimumab, treatment strategies for patients with advanced hepatocellular carcinoma (HCC) have markedly evolved, and discussions on conversion therapy - which, broadly speaking, combines these systemic therapies with locoregional modalities - have become commonplace. However, the term "conversion therapy" has not yet been clearly defined, making it difficult to compare treatment outcomes among studies. To address this issue, the Japan Liver Cancer Association established a consensus-based "Working Group on the Definition of Conversion" as an official project of the association. The working group comprised experts in hepatobiliary surgery, hepatology, and radiology, with a rapporteur responsible for drafting and revising the definitions. The group proposed standardized definitions for "conversion surgery," "neoadjuvant therapy," and "ablation as conversion therapy," while recommending that transcatheter arterial chemoembolization should not be classified as conversion therapy due to its limited curative potential. The definitions also introduced two key concepts: functional conversion (based on the hepatic functional reserve) and oncological conversion (based on the tumor status). Adoption of these definitions is expected to facilitate appropriate evaluation of pretreatments and outcomes of conversion therapy. Ultimately, these efforts are expected to contribute to refining clinical decision-making, providing a common framework for guideline development and future clinical studies, and improving the outcomes of multidisciplinary treatments for advanced HCC; however, further validation is required.