Hepatocellular Carcinoma and Health-Related Quality of Life: A Systematic Review of Outcomes From Systemic Therapies.

Aim: Poor outcomes in advanced hepatocellular carcinoma (HCC) coupled with potential significant treatment side effects underpin a strong rationale to assess health-related quality of life (HRQOL) in those treated with systemic therapies. This study is aimed at quantifying the effect of systemic therapies on HRQOL outcomes in HCC patients when compared to baseline or placebo, other systemic therapies, and transarterial radioembolisation (TARE). Methods: In May 2024, two independent reviewers searched PubMed, EMBASE, and Google Scholar for studies comparing postsystemic therapy HRQOL scores in adult patients with HCC to baseline or placebo, other systemic therapies, or to TARE. Narrative synthesis was used to synthesise results. Risk of bias was assessed using RoB 2 and ROBINS-I. This review was structured according to PRISMA guidelines and was prospectively registered in the PROSPERO register (CRD42024521699). Results: Twenty-nine studies with 10,472 patients using eight HRQOL instruments were included. Compared to baseline, patients on atezolizumab/bevacizumab and sorafenib both experienced significant declines in HRQOL, and lenvatinib nonsignificantly decreased HRQOL. HRQOL remained unchanged in patients on pembrolizumab or nivolumab. Atezolizumab/bevacizumab and lenvatinib both significantly delayed HRQOL deterioration compared to sorafenib. Compared to TARE, atezolizumab/bevacizumab delayed time-to-deterioration in HRQOL, whereas sorafenib had significantly worse HRQOL. Conclusion: Despite worsening HRQOL outcomes compared to baseline, the first-line agents atezolizumab/bevacizumab and lenvatinib had superior HRQOL outcomes in comparison to sorafenib. Sorafenib significantly worsened HRQOL compared to TARE. As the majority of included studies included sorafenib, which has been largely superseded by newer therapies, further trials evaluating HRQOL with these newer therapies are required.