Precision Locoregional Therapy Combined with Immune Checkpoint Blockade for Intermediate-Advanced Hepatocellular Carcinoma

Abstract

Background:

The potential value of combining transarterial chemoembolization (TACE) with immune checkpoint inhibitors (ICIs) for hepatocellular carcinoma (HCC) at intermediate-to-advanced stages remains incompletely defined. This study sought to characterize the efficacy and tolerability of this combined approach and to delineate pretreatment characteristics linked to patient prognosis.

Methods:

A retrospective analysis was conducted on 248 consecutive HCC patients managed between January 2020 and December 2024. Treatment allocation at the time of initial decision resulted in 126 patients receiving TACE in conjunction with ICIs, whereas 122 were managed with TACE as the sole intervention. Radiological response was independently adjudicated according to the modified Response Evaluation Criteria in Solid Tumors. Survival endpoints—namely progression-free survival (PFS) and overall survival (OS)—were derived via the Kaplan–Meier methodology, with prognostic determinants explored through Cox regression modeling.

Results:

The addition of ICIs to TACE conferred a substantially higher objective response rate (46.0% vs. 24.6%, p < 0.001) and disease control rate (77.8% vs. 59.8%, p = 0.003). The combination arm demonstrated a median PFS of 10.8 months, compared with 5.6 months in patients receiving TACE alone (p < 0.001); corresponding median OS figures were 21.6 and 14.2 months (p < 0.001). On multivariate Cox analysis, an Eastern Cooperative Oncology Group (ECOG) performance status of 2, serum α-fetoprotein (AFP) ≥400 ng/mL, portal vein tumor thrombus (PVTT), extrahepatic disease extension, and a neutrophil-to-lymphocyte ratio ≥5 each emerged as independent predictors of inferior PFS. Shorter OS was independently linked to ECOG 2, Child–Pugh class B, elevated AFP, PVTT, and distant metastases. Across both endpoints, the combination strategy retained independent prognostic significance (both p < 0.001). Serious immune-mediated toxicity (grades 3 and 4) was recorded in 15.1% of patients; 9.5% required permanent ICI discontinuation, and no fatality attributable to treatment was observed.

Conclusions:

In this real-world retrospective series, the integration of ICIs into TACE-based treatment was associated with meaningful gains in tumor response and survival among patients with intermediate-to-advanced HCC, without generating unacceptable safety signals. Stratification by functional status, hepatic functional reserve, AFP burden, vascular invasion, metastatic spread, and inflammatory markers may enhance individualized prognostic assessment in this population.