Beyond second-line therapy: Strategic sequencing of systemic treatments in advanced hepatocellular carcinoma.

This review integrates evidence from phase II and III trials and real-world studies, including more than 4000 patients across different global regions, to outline how sequencing beyond first-line immunotherapy is redefining clinical practice.

本综述整合了II期和III期试验以及真实世界研究的证据，包括来自不同全球地区的超过4000名患者，以概述如何在一线免疫治疗之外进行治疗序列的重新定义临床实践。

After immune-based combinations, tyrosine kinase inhibitors remain active and feasible options, achieving a median overall survivalof ~10-11 months, while preservation of liver function consistently determines treatment eligibility and postprogression survival. Incorporation of the Barcelona Clinic Liver Cancer concept "upon response" refines classification for patients achieving major responses or conversion and aligns staging with contemporary treatment dynamics.

在基于免疫的联合治疗之后，酪氨酸激酶抑制剂仍然是活跃且可行的选择，实现了中位总生存期约为10-11个月，而肝功能的保持始终决定了治疗资格和疾病进展后的生存。

The CUSE framework-encompassing complexity, uncertainty, subjectivity, and emotion-reframes sequencing as an adaptive, patient-centered, and multifaceted process that integrates toxicity, feasibility, and patient values alongside efficacy.

巴塞罗那临床肝癌概念的纳入“在反应后”对达到主要反应或转化的患者进行分类细化，并使分期与当代治疗动态保持一致。

By structuring diverse clinical inputs into a unified interpretive model, CUSE supports multidisciplinary reasoning and enhances conceptual coherence in treatment sequencing.

CUSE框架——包括复杂性、不确定性、主观性和情感——将治疗序列重新构架为一个适应性强、以患者为中心、多方面的过程，该过程整合了毒性、可行性以及患者价值观和疗效。

Conversion therapy and "drug-off" strategies following complete or major responses represent emerging frontiers, emphasizing that sequencing in HCC now extends beyond second-line therapy.

通过将多样化的临床输入构建为一个统一的解释模型，CUSE支持多学科推理，并增强了治疗序列中的概念一致性。

Additionally, preserving hepatic function and applying polyhedral, data-informed decision frameworks are key to sustaining eligibility and optimizing outcomes across the continuum of care.

转化治疗和在完全或主要反应后的“药物关闭”策略代表了新兴的前沿，强调了HCC的治疗序列现在已扩展到二线治疗之外。