A recent systematic review and meta-analysis published in JAMA Network Open has provided a comprehensive comparison of locoregional therapies (LRTs) for nonmetastatic hepatocellular carcinoma (HCC). The study, encompassing 40 randomized clinical trials with a total of 11,576 patients, reveals significant differences in efficacy among various LRTs, impacting both progression-free survival (PFS) and overall survival (OS).
The meta-analysis indicates a hierarchical structure in the effectiveness of LRTs. Surgical approaches, particularly when combined with adjuvant therapies like radiation therapy (RT) or hepatic arterial infusion chemotherapy (HAIC), demonstrated the most favorable outcomes. In contrast, embolization-based therapies such as transarterial chemoembolization (TACE) and transarterial radioembolization (TARE) were associated with poorer results.
Surgical Interventions vs. Ablation
The analysis showed that surgery combined with adjuvant therapy significantly improved both PFS (HR, 0.62; 95% CI, 0.51-0.75; P < .001) and OS (HR, 0.61; 95% CI, 0.48-0.78; P < .001) compared to surgery alone. Furthermore, surgery was superior to radiofrequency ablation (RFA) in terms of PFS (HR, 0.74; 95% CI, 0.63-0.87; P < .001) and OS (HR, 0.71; 95% CI, 0.54-0.95; P = .02).
Radiotherapy and HAIC
RT demonstrated better outcomes than TACE, with a hazard ratio for PFS of 0.35 (95% CI, 0.21-0.60; P < .001) and for OS of 0.35 (95% CI, 0.13-0.97; P = .04). Similarly, HAIC outperformed TACE in both PFS (HR, 0.57; 95% CI, 0.45-0.72; P < .001) and OS (HR, 0.58; 95% CI, 0.45-0.75; P < .001).
Embolization-Based Therapies
Embolization-based therapies, including TACE, TAE, and TARE, generally showed less favorable outcomes compared to surgical or ablative approaches. TACE appeared similar to bland TAE (PFS: HR, 1.37 [95% CI, 0.91-2.05]; P = .13; OS: HR, 1.31 [95% CI, 0.81-2.12]; P = .27), but TACE-based treatment appeared to be associated with better outcomes than tyrosine kinase inhibitor (TKI) monotherapy (PFS: HR, 0.36 [95% CI, 0.23-0.56]; P < .001; OS: HR, 0.50 [95% CI, 0.37-0.66]; P < .001).
Implications for Clinical Practice
The study's findings underscore the need for individualized treatment strategies in managing HCC. According to the researchers, the choice of LRT should be carefully considered based on patient-specific factors and the stage of the disease. "Our findings suggest that LRT remains an important tool in treating hepatocellular carcinoma and, for patients eligible for LRTs, some forms of LRT may be favored over others," the authors noted.
The research team, led by Krishnan R. Patel, MD, MHS, from the National Cancer Institute, emphasized that while surgical management remains a preferred standard of care for eligible patients, adjuvant treatment may further improve outcomes. For unresectable disease, non-embolization-based treatments like RFA, MWA, RT, and HAIC appear to offer better results than embolization-based procedures.
Future Directions
The authors call for further research to validate these findings in multi-arm randomized trials and individual patient-level meta-analyses. They also highlight the importance of exploring the role of immunotherapy in combination with LRT, as several ongoing trials are investigating these approaches.
This meta-analysis provides valuable insights into the comparative effectiveness of different LRTs for HCC, guiding clinicians in making informed treatment decisions and ultimately improving patient outcomes.
