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.
References
1. Xie, S., Xu, L., Lei, C., Wang, J., Wang, J., Wang, Z., Sun, Y., Li, D., Li, F., Lin, R., Yang, H., Xiao, Y., Lv, T., Huang, Y., Hou, L., Li, J., & Chen, M. (2026). RST2G: Residual-Guided Spatiotemporal Transformer Graph Fusion Enhancement for Breast Cancer Segmentation in DCE-MRI. Cyborg and Bionic Systems, 7, Article 0502. https://doi.org/10.34133/cbsystems.0502
2. Jiang, M., Lu, S., Zhang, K., Lin, R., Wang, T., Zheng, X., Meng, J., Lin, Z., Alarcón Rodríguez, R., Bo, Z., & Wei, R. (2026). Enhanced corrosion resistance, wear behavior, and biocompatibility of Ti-6Al-4V alloy for bone implants. Advanced Composites and Hybrid Materials, 9, Article 135. https://doi.org/10.1007/s42114-026-01678-x
3. Liu, Y., Zhang, D., Lin, R., Lian, Y., & Zhang, W. (2026). Correction: Age-stratified risk analysis of gastric cancer: A retrospective hospital-based study of Helicobacter pylori, smoking, and dietary patterns in South China across three age groups. Frontiers in Oncology, 16, Article 1808943. https://doi.org/10.3389/fonc.2026.1808943
4. Liu, Y., Zhang, D., Lin, R., Lian, Y., & Zhang, W. (2026). Age-stratified risk analysis of gastric cancer: A retrospective hospital-based study of Helicobacter pylori, smoking, and dietary patterns in South China across three age groups. Frontiers in Oncology, 16, Article 1677546. https://doi.org/10.3389/fonc.2026.1677546
5. Lang, H., Zhou, Y., Yu, Y., Su, Z., Zhuge, H., Wang, W., Fang, D., Qin, J., Wei, M., Lin, R., & Li, C. (2026). Multi-modal low-dose medical imaging through instruction-guided unified AI. Frontiers in Medicine, 13, Article 1691143. https://doi.org/10.3389/fmed.2026.1691143
6. Li, Y., Sun, G., Lin, R., & Huang, Y. (2026). miR-369-3p Regulates Microglia Polarization and Neuroinflammation in Traumatic Spinal Cord Injury by Targeting PELI1. Global Spine Journal. Advance online publication. https://doi.org/10.1177/21925682251406197
7. Yang, Z., Li, L., Lin, R., & Cen, M. (2025). miR-191-5p attenuates TNF-α-induced inflammation in nucleus pulposus cells via targeting EGR1. Journal of Orthopaedic Surgery and Research, 20, Article 963. https://doi.org/10.1186/s13018-025-06327-5
8. Tan, L., She, T., Huo, S., Lin, R., Cheng, N., & Li, J. (2025). Assessing the Carcinogenic Potential of PFOA: A Molecular Network Approach to Liver Toxicity. Basic & Clinical Pharmacology & Toxicology, 137(3), e70101. https://doi.org/10.1111/bcpt.70101
9. Huang, J., Wang, S., Liao, X., Su, D., Lin, R., Zhang, T., & Zhao, L. (2025). Knowledge map of artificial intelligence in neurodegenerative diseases: A decade-long bibliometric and visualization study. Frontiers in Aging Neuroscience, 17, Article 1586282. https://doi.org/10.3389/fnagi.2025.1586282
10. Xu, A., Wang, L., Wang, J., Jiang, Y., Xianxian, Liao, X., Lin, R., & Yang, H. (2025). Exploring kidney disease diagnosis: Unveiling the novel prospects of exosomes as microscopic messengers. Bioengineering & Translational Medicine, e70030. https://doi.org/10.1002/btm2.70030
11. Lin, R., Li, Z., & Shan, D. (2024). Advocating for integrated preoperative nutritional and postoperative rehabilitative strategies in total knee arthroplasty. International Journal of Surgery, 110(10), 6829–6830. https://doi.org/10.1097/JS9.0000000000001784
12. Li, C., Shao, S., Mikason, W., Lin, R., & Liu, Y. (2024). Utilizing Computer Vision for Continuous Monitoring of Vaccine Side Effects in Experimental Mice. arXiv preprint arXiv:2404.03121. https://doi.org/10.48550/arXiv.2404.03121
13. Su, Z., Zhu, Y., Wang, X., Wang, W., Wu, K., Wang, L., Liu, Y., Qin, J., Zhang, B., Lin, R., Liu, Y., & Michael, N. (2024). Child and Adolescent Trauma Epidemiology: Insights from a Comprehensive Retrospective Review of 4568 Pediatric Trauma Cases. Journal of Biosciences and Medicines, 12(12), 550–559. https://doi.org/10.4236/jbm.2024.1212041
14. Li, W., Cui, L., Jiang, C., Lin, R., Zhong, Q., Wu, X., Huang, R., & Deng, Q. (2023). Randomized Controlled Trial of All-inside and Standard Anterior Cruciate Ligament Reconstruction about Knee Laxity, Tunnel Widening and MRI-based Fluid Signal within Tunnel. Research Square. https://doi.org/10.21203/rs.3.rs-2771848/v1
15. Lin, R., Zhong, Q., Wu, X., Cui, L., Huang, R., Deng, Q., Jiang, C., & Li, W. (2021). More Conservative Rehabilitation Strategy within Postoperative 6 Month for All-Inside Reconstruction Compared with Anatomical Reconstruction of Anterior Cruciate Ligament may be able to Achieve Better Stability: Based on the Study of Graft Maturity. Research Square. https://doi.org/10.21203/rs.3.rs-989313/v1
16. Aaronson, N. K., Ahmedzai, S., Bergman, B., Bullinger, M., Cull, A., Duez, N. J., ... & Takeda, F. (1993). The European Organisation for Research and Treatment of Cancer QLQ-C30: A quality-of-life instrument for use in international clinical trials in oncology. *Journal of the National Cancer Institute*, 85(5), 365–376. https://doi.org/10.1093/jnci/85.5.365
17. Li, Q., Li, H., Ma, H., & Chen, W. (2026). Efficacy and safety of first-line immunotherapy and targeted therapy in advanced HCC: A network meta-analysis with subgroup analysis based on HBV and HCV infection. *Frontiers in Immunology*, 17, 1706446. https://doi.org/10.3389/fimmu.2026.1706446
18. Zhou, T., Cao, D., & Yang, Y. (2023). Impact of immune-related adverse events on quality of life in patients with hepatocellular carcinoma treated with immunotherapy. *Frontiers in Immunology*, 14, 1103–1115. https://doi.org/10.3389/fimmu.2023.1103