Treatment for intermediate and advanced-stage hepatocellular carcinoma: does systemic therapy synergize the therapeutic efficacy of TACE?

Background: Transarterial chemoembolization (TACE) is a standard treatment for intermediate-stage hepatocellular carcinoma (HCC), but its efficacy varies due to patient heterogeneity. Combining TACE with systemic therapies, such as targeted agents or immune checkpoint inhibitors, has shown promise in improving outcomes, though controversies regarding survival benefits and safety persist. This study investigates whether synchronized systemic therapy enhances the therapeutic efficacy of TACE in intermediate and advanced-stage HCC. Methods: This single-center, retrospective study included 142 patients with intermediate and advanced-stage HCC (BCLC B or C) who received TACE as initial treatment between February 2019 and August 2022 at Hunan Provincial People's Hospital. Patients were divided into two groups: combination therapy (TACE plus systemic therapy, n=41) and TACE monotherapy (n=101). Progression-free survival (PFS), overall survival (OS), treatment response (per mRECIST criteria), and adverse events (AEs) were compared. Cox regression and Kaplan-Meier analyses were used to assess survival outcomes. Results: No significant differences were observed in baseline characteristics, except for a higher proportion of Child-Pugh A patients in the combination group (90.2% vs. 67.3%, P= 0.005). Median PFS was similar between the combination and monotherapy groups (5.5 vs. 6.0 months, P= 0.832), with no significant differences in BCLC-B (18.3 vs. 17.4 months, P= 0.516) or BCLC-C (4.1 vs. 3.7 months, P= 0.255) subgroups. However, the combination group showed a trend toward improved OS (24.8 vs. 16.7 months, P= 0.282), with a significant benefit in BCLC-C patients (17.9 vs. 11.0 months, P= 0.048). Grade 3 or 4 AEs were comparable between groups (7.2% vs. 14.9%, P= 0.187). Conclusion: Combining systemic therapy with TACE does not improve PFS but may enhance OS in BCLC-C patients. The safety profile is comparable, particularly in patients with preserved liver function. These findings highlight the importance of patient selection and warrant further prospective studies to optimize treatment strategies.