Impact of Consolidative Therapies After Transarterial Chemoembolization for Unresectable Hepatocellular Carcinoma: A Real-World Database Analysis

Purpose: Outcomes for unresectable hepatocellular carcinoma (HCC) using transarterial chemoembolization (TACE) alone remain poor, with two-year survival ranging from 30-60% and nearly all patients developing disease progression after treatment. This study aims to investigate whether the addition of consolidative transarterial radioembolization (TARE), radiofrequency ablation (RFA), or stereotactic body radiation therapy (SBRT) after TACE can improve overall survival (OS) or progression free survival (PFS) in patients with unresectable HCC.

Methodology: The Flatiron Health database is a nationwide longitudinal de-identified database derived from electronic health record (EHR) data from approximately 280+ cancer clinics (~800 sites of care). We included patients with nonmetastatic unresectable HCC treated with local therapy from January 2010 to January 2020 and generated baseline descriptive characteristics. We analyzed OS and PFS using log rank and Cox proportional hazards regression. Date of first local therapy administration was considered the index date for time-dependent analyses.

Results: 1342 patients were included in our analysis with a median follow-up of 54 months. 898 patients received TACE alone, 194 received TACE+TARE, 184 received TACE+RFA, and 66 received TACE+SBRT. The median age was 65 years old, with the majority of patients being male (78%), white (61%), and ECOG 0-1 (83%). 51% of patients received systemic therapy. The only significant difference between treatment groups was that the TACE+TARE arm had a higher rate of systemic therapy use (69%). On log rank test and Cox proportional hazards regression, consolidative RFA and SBRT resulted in improved OS and PFS compared to TACE alone, while consolidative TARE did not. Subset analysis showed that the benefit of consolidative RFA was not seen in patients with T3-4 lesions, whereas the benefit of consolidative SBRT persisted in this patient population. Although consolidative TARE offered no OS benefit to patients with T1-2 lesions, the OS benefit of consolidative TARE was significant in patients with T3-4 lesions.

Conclusions: Patients with unresectable HCC treated with consolidative therapies (RFA and SBRT) after TACE had improved OS and PFS compared to TACE alone. Consolidative SBRT had the most significant impact, improving outcomes in HCC regardless of tumor size, while the other consolidative therapies had varying efficacy for T1-2 vs. T3-4 lesions. Larger prospective phase II/III trials are warranted to further investigate the role of consolidative therapies after TACE.

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