Converse therapeutic hierarchy in hepatocellular carcinoma

Abstract

The therapeutic landscape of hepatocellular carcinoma (HCC) is undergoing a substantial transformation driven by advances in systemic therapies and locoregional treatments. High response rates observed with immune checkpoint inhibitors and combination regimens have opened the door to conversion therapy. Initially unresectable or non-curable patients can achieve a tumour downsizing to access potentially curative options such as surgery, ablation, or transplantation. This evolving strategy is framed within the concept of the converse therapeutic hierarchy, which promotes a dynamic, response-guided approach. In this model, every treatment is no longer a terminal option but a potential gateway to curative interventions. This review explores the clinical rationale and current evidence supporting conversion therapy in HCC, detailing systemic regimens, transarterial and percutaneous treatments, and their integration into multimodal strategies. Emphasis is placed on response-guided treatment reassessment, perioperative immunotherapy, and the potential of tailored sequencing to redefine clinical practice in HCC. Barriers such as biological heterogeneity, the lack of predictive biomarkers, and organisational gaps in multidisciplinary coordination remain significant. At the same time, improvements in systemic efficacy, advances in locoregional techniques, and new evidence from real-world data point toward a future in which therapeutic intent is no longer fixed but can evolve according to patient response. Conversion therapy, once aspirational, is becoming a realistic and strategic objective in modern HCC care.

Keywords

Hepatocellular carcinoma / conversion / multidisciplinary / systemic treatment / selective internal radiotherapy / transplantation / resection / liver

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