Systemic-Locoregional Sequencing in HCC: Neoadjuvant Protocols and Downstaging

Hepatocellular carcinoma (HCC) management is rapidly evolving as systemic therapies and locoregional treatments are increasingly combined across disease stages. Yet, many practical questions remain unresolved: Which patients benefit most from neoadjuvant systemic therapy before resection, ablation, or liver transplantation? What is the best sequencing and timing of transarterial therapies, radiotherapy, and ablation in the era of immunotherapy and modern targeted agents? How should response be assessed to guide downstaging decisions, and how can clinicians balance oncologic control with preservation of liver function?



This Research Topic aims to bring together translational and clinical evidence on systemic–locoregional sequencing strategies in HCC, with a focus on neoadjuvant protocols, conversion therapy, and downstaging pathways. We welcome contributions that clarify patient selection, treatment algorithms, safety, and real-world feasibility, including multidisciplinary approaches that integrate hepatology, interventional oncology, surgery, and transplant medicine.



Areas of interest include (but are not limited to): neoadjuvant and perioperative systemic therapy; immunotherapy- and targeted therapy–based combinations with TACE, TARE, HAIC, SBRT, or ablation; biomarkers and imaging for response and liver reserve; definitions and endpoints for downstaging and conversion; bridging therapy to transplant; management of adverse events and hepatic decompensation risk; and prospective trials, registries, and high-quality real-world studies.



The goal of this Topic is to support evidence-based, patient-centered sequencing that improves resectability, transplant eligibility, and long-term outcomes in HCC within the scope of Gastroenterology and Cancer. (frontiersin.org)