Keywords
hepatocellular carcinoma
patient-reported outcomes
Abstract
The landscape of first-line systemic therapy for advanced hepatocellular carcinoma (HCC) has undergone transformative change over the past five years, with immune checkpoint inhibitor–based regimens and targeted therapies demonstrating meaningful survival improvements in landmark randomized controlled trials. However, the comparative evaluation of these regimens has relied predominantly on investigator-assessed endpoints such as overall survival (OS) and progression-free survival (PFS), which do not fully capture the patient experience during treatment. Patient-reported outcomes (PROs) and health-related quality of life (HRQoL) represent complementary dimensions of treatment value that are particularly salient in advanced HCC, where baseline symptom burden is high and treatment-related toxicities can substantially impair functional well-being. This paper synthesizes PRO evidence from the seven pivotal first-line randomized controlled trials in advanced HCC—IMbrave150, HIMALAYA, LEAP-002, ORIENT-32, CARES-310, CheckMate 459, and RATIONALE-301—and integrates these findings with the network meta-analysis by Li et al. (2026), which aggregated efficacy and safety data across 24 RCTs and 13,572 patients. We argue that PROs and symptom burden must be integrated alongside survival endpoints to guide truly patient-centered first-line decision-making. A PRO-informed treatment selection framework is proposed, accounting for baseline symptom burden, performance status, liver function, and etiology. Future directions including digital PRO collection, real-world PRO evidence, and artificial intelligence–based prediction models are discussed.
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