Combined treatments based on interventional therapy improve the prognosis of patients with HCC: an umbrella review of systematic reviews and meta-analyses.

[OBJECTIVE] To evaluate the quality of evidence on interventional therapies-alone or in combination-for improving the prognosis of hepatocellular carcinoma (HCC).

[METHODS] We systematically analyzed 127 meta-analyses (472 outcomes) retrieved from PubMed, Embase, Web of Science, and Cochrane (to November 2024) and assessed quality using AMSTAR and GRADE.

[RESULTS] High-quality evidence indicated that transcatheter arterial chemoembolization (TACE) combined with multimodal therapies significantly improved survival and tumor response versus monotherapy. TACE plus lenvatinib enhanced objective response rate (ORR; odds ratio [OR] = 3.58, 95 % CI 2.45-5.24) and overall survival (OS; hazard ratio [HR] = 0.47, 95 % CI 0.35-0.62). TACE plus sorafenib improved ORR (relative risk [RR] = 1.35, 95 % CI 1.24-1.48), and TACE plus apatinib improved 1-year survival (OR = 2.28, 95 % CI 1.44-3.62). Local adjuncts such as I seeds (3-year OS: OR = 3.13, 95 % CI 1.68-5.83) and external beam radiotherapy (1-year mortality: RR = 0.51, 95 % CI 0.41-0.62) further amplified benefits. Immunotherapy combinations (TACE + thalidomide) increased ORR (OR = 1.84, 95 % CI 1.34-2.52) and disease control rate (OR = 2.68, 95 % CI 1.80-3.99). However, TACE plus multi-kinase inhibitors (MKIs) raised serious adverse events by 41 % (RR = 1.41, 95 % CI 1.25-1.59). Although most outcomes (87.5 %) were graded low or very low quality due to heterogeneity and publication bias.

[CONCLUSION] Combination strategies based on interventional therapy improve HCC prognosis, though TACE plus MKIs increases SAEs. High-quality, large-scale trials are needed to validate efficacy, optimize safety, and inform clinical guidelines.