{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,20]],"date-time":"2026-04-20T16:51:21Z","timestamp":1776703881551,"version":"3.51.2"},"reference-count":46,"publisher":"S. Karger AG","license":[{"start":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T00:00:00Z","timestamp":1771459200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T00:00:00Z","timestamp":1771459200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Liver Cancer"],"abstract":"<jats:p>Introduction: Transarterial chemoembolisation (TACE) is considered the standard-of-care for patients with intermediate-stage hepatocellular carcinoma (HCC), despite several patients exhibit features that may be associated with suboptimal outcome of treatment \u2013 also referred to as TACE-unsuitable. In this study, our aim was to provide real-world evidence that patients who are considered TACE-unsuitable may receive greater benefit by systemic therapy than by TACE. Methods: This study analysed 1,150 patients with TACE-unsuitable HCC, defined according to Asia-Pacific Primary Liver Cancer Expert criteria. Patients were initially treated with TACE (n = 842), sorafenib (n = 96), lenvatinib (n = 62), or atezolizumab\/bevacizumab (n = 47). Overall survival (OS) was the primary endpoint. Inverse probability of treatment weighting was applied to adjust for baseline differences. Results: Compared to TACE, atezolizumab\/bevacizumab reduced mortality risk (hazard ratio [HR]: 0.47, 95% confidence interval [95% CI]: 0.27\u20130.80; p = 0.008), lenvatinib was neutral (HR: 0.62, 95% CI: 0.35\u20131.08; p = 0.091), and sorafenib was associated with increased mortality (HR: 1.85, 95% CI: 1.28\u20132.65; p = 0.001). OS at 24 months was 60.2% for TACE, 31.9% for sorafenib, 68.3% for lenvatinib, and 70.5% for atezolizumab\/bevacizumab (p &lt; 0.0001). The disease control rate was 53.2% with TACE, 47.9% with sorafenib, 67.8% with lenvatinib (p = 0.030 versus TACE; p = 0.025 versus sorafenib), and 75.6% with atezolizumab\/bevacizumab (p &lt; 0.001 versus TACE; p &lt; 0.001 versus sorafenib). Conclusions: In TACE-unsuitable patients, systemic treatment with atezolizumab\/bevacizumab and, to a lesser extent, lenvatinib is associated with improved outcome compared to TACE. These findings support a paradigm shift in the initial management of intermediate-stage HCC, favouring the early use of systemic therapy in appropriately selected patients.<\/jats:p>","DOI":"10.1159\/000551050","type":"journal-article","created":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T17:00:51Z","timestamp":1771520451000},"page":"1-17","source":"Crossref","is-referenced-by-count":0,"title":["Comparative Efficacy of Initial Treatment Strategies in Patients with Transarterial Chemoembolisation-Unsuitable Hepatocellular Carcinoma"],"prefix":"10.1159","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8526-837X","authenticated-orcid":false,"given":"Edoardo 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