Treatment Strategies for Hepatocellular Carcinoma: When Less is Not More

The arsenal of therapeutic options for HCC ranges from surgical strategies such as resection and Liver Transplantation (LT) to Locoregional Therapies (LRT), including ablation and transarterial procedures. Recently, the pool of resources available to treat HCC has been expanded with randomized clinical trials demonstrating the effectiveness of immune checkpoint inhibitors for the treatment of advanced HCC. Despite the wide variety of treatment options, tailoring the best strategy to each patient remains challenging. Several combinations of different treatments have been utilized in different clinical scenarios. In the setting of unresectable HCC, combining TACE with an ablation procedure such as Radiofrequency Ablation (RFA) or Microwave Ablation (MWA) is associated with improved outcomes over Transarterial Chemoembolization (TACE) alone. Additionally, TACE can be utilized as an adjuvant treatment for resected HCC with narrow margins. Patients waiting for LT may be treated with TACE combined with RFA or percutaneous ethanol injection to prevent tumor progression beyond the acceptable LT threshold. Immune checkpoint inhibitors given as adjuvant treatment following liver resection or TACE seem to improve recurrence-free survival. Finally, several trials are underway to investigate the role of immune checkpoint inhibitors as neoadjuvant therapy prior to liver resection. In conclusion, in many clinical settings, combining different approaches surpasses monotherapy for the treatment of HCC. Thus, the maxim "less is more" seems not to have stood the test of time.