Highlight
This review synthesizes evidence from over 4,000 advanced hepatocellular carcinoma (HCC) patients worldwide, emphasizing that systemic therapy sequencing has evolved beyond linear second-line algorithms. Key highlights include: 1) The sustained efficacy of tyrosine kinase inhibitors (TKIs) following first-line immune-based combinations, demonstrating median overall survival around 10-11 months; 2) The critical role of preserved liver function in guiding treatment eligibility and influencing survival post-progression; 3) The introduction of the BCLC-UR classification, which enhances staging by considering treatment response and conversion; 4) The novel CUSE framework (Complexity, Uncertainty, Subjectivity, and Emotion), which underpins adaptive, patient-centered sequencing integrating clinical efficacy with toxicity, feasibility, and patient values.
