{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T06:04:30Z","timestamp":1789365870385,"version":"build-2803163510"},"reference-count":86,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T00:00:00Z","timestamp":1789344000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Oncol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>This study evaluated the efficacy of transarterial chemoembolization (TACE) combined with anti-vascular endothelial growth factor (VEGF)\/tyrosine kinase inhibitors (TKIs) and programmed cell death protein 1 (PD-1)\/programmed cell death protein ligand 1 (PD-L1) inhibitors in the treatment of unresectable hepatocellular carcinoma (uHCC).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Four databases were searched for studies evaluating the efficacy of TACE combined with anti-VEGF\/TKIs and PD-1\/PD-L1 inhibitors in uHCC. Pooled data were analyzed using random-effects models, with hazard ratio (HR) and 95% confidence intervals reported. Overall survival (OS) was the primary outcome, and progression-free survival (PFS) was a secondary outcome. Subgroup analyses were performed based on treatment regimens, therapy setting, and the sequencing of TACE and systemic therapy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>A total of 53 studies (3 multicentre randomized controlled trials (RCTs) and 50 cohort studies) comprising over 10, 000 patients were included. Patients receiving triple therapy may derive greater OS (HR\u00a0=\u00a00.47, p&amp;lt;0.001) and PFS (HR\u00a0=\u00a00.52, p&amp;lt;0.001) benefits than those receiving other regimens. In OS subgroups, across various combinations, the TACE-bevacizumab-atezolizumab (HR\u00a0=\u00a00.44, p&amp;lt;0.001) and TACE-lenvatinib-tislelizumab regimens (HR\u00a0=\u00a00.44, p&amp;lt;0.001) appear to derive greater benefit. In contrast, the TACE-lenvatinib-pembrolizumab combination appears to show less benefit (HR\u00a0=\u00a00.67, p&amp;lt;0.001). Additionally, patients could potentially carry greater OS benefit with triple therapy, regardless of whether TACE was performed first (HR\u00a0=\u00a00.46, p&amp;lt;0.001) or systemic therapy was followed by TACE (HR\u00a0=\u00a00.42, p=0.001). Regarding treatment setting, the first-line group may obtain greater OS benefit (HR\u00a0=\u00a00.47, p&amp;lt;0.001), and the non-first-line group may also derive greater benefit (HR\u00a0=\u00a00.34, p=0.001).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Triple therapy (TACE with anti-VEGF\/TKIs and PD-1\/PD-L1 inhibitors) could significantly improve prognosis in uHCC, and its efficacy may vary depending on the treatment regimen, including the drug combination, treatment sequence, and lines.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Systematic Review Registration<\/jats:title>\n                    <jats:p>\n                      <jats:ext-link>https:\/\/www.crd.york.ac.uk\/PROSPERO\/view\/CRD420251151703<\/jats:ext-link>\n                      , identifier CRD420251151703.\n                    <\/jats:p>\n     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