Efficacy and safety of TACE/HAIC combined with targeted-immunotherapy versus targeted-immunotherapy alone in Vp3-4 hepatocellular carcinoma: a propensity score-matched retrospective cohort study based on two-center data

To evaluate the efficacy and safety of transarterial chemoembolization (TACE)/hepatic arterial infusion chemotherapy (HAIC) combined with targeted-immunotherapy versus targeted-immunotherapy alone in patients with Vp3-4 hepatocellular carcinoma (HCC). This retrospective study enrolled 92 patients with Vp3-4 HCC from two centers. Propensity score matching (PSM) at a 1:2 ratio was performed to balance baseline characteristics, yielding 48 patients in the combination therapy group and 31 in the systemic therapy alone group. Objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and treatment-related adverse events were compared between groups. After PSM, the combination therapy group demonstrated a significantly higher ORR (64.58% vs. 22.58%, P < 0.001) and significantly longer median OS (14.2 vs. 7.7 months, hazard ratio [HR] = 0.481, P = 0.003), whereas the difference in median PFS was not statistically significant (5.8 vs. 4.1 months, P = 0.205). Multivariable Cox analysis showed that combination therapy was associated with a lower risk of death (HR = 0.451, P = 0.001). Exploratory subgroup analysis suggested that patients with albumin-bilirubin (ALBI) grade 2–3 may derive greater benefit from combination therapy. The incidence of grade ≥3 liver-related adverse events was higher in the combination group (25.00% vs. 6.45%, P = 0.035), but all events were reversible and no treatment-related death occurred. In Vp3-4 HCC patients with tolerable hepatic function, the addition of TACE/HAIC to targeted-immunotherapy is associated with prolonged OS with manageable safety profiles. Patients with ALBI grade 2–3 may represent a potential advantaged subgroup, which warrants prospective validation.