Multiple systemic agents have recently been approved in the first- and second-line setting for hepatocellular carcinoma (HCC), increasing the therapeutic options for patients and treating physicians. The randomised controlled trials that led to these approvals were predominantly conducted in a population comprised of patients with advanced HCC. However, these trials also included a subset of patients who had progressed after locoregional therapies (LRTs), mostly transarterial chemoembolisation. With a greater number of systemic agents available, the role of LRTs has become a topic of debate, specifically regarding when to transition to systemic therapy in unresectable HCC and the potential opportunities for combining locoregional and systemic therapies. Trials of immuno-oncology agents (notably T cell checkpoint inhibitors) are ongoing in the advanced disease setting and these agents also present opportunities for combination therapies, both with other systemic agents and with LRTs in earlier stage disease. This article will review strategies to guide patient selection for LRT as well as the development of locoregional-systemic combinations based on scientific rationale and the challenges of clinical trial design in this setting.

中文翻译：

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局部治疗在全身治疗后的作用

最近，多种全身性药物被批准用于肝细胞癌 (HCC) 的一线和二线治疗，增加了患者和治疗医师的治疗选择。导致这些批准的随机对照试验主要在由晚期 HCC 患者组成的人群中进行。然而，这些试验还包括在局部治疗 (LRT) 后出现进展的一部分患者，主要是经动脉化疗栓塞。随着越来越多的全身药物可用，LRT 的作用已成为一个争论的话题，特别是关于何时在不可切除的 HCC 中过渡到全身治疗以及结合局部和全身治疗的潜在机会。免疫肿瘤药物（特别是 T 细胞检查点抑制剂）的试验正在晚期疾病环境中进行，这些药物也提供了与其他全身性药物和早期疾病的 LRT 联合治疗的机会。本文将回顾指导 LRT 患者选择的策略，以及基于科学原理和临床试验设计在这种情况下的挑战的局部区域系统组合的开发。