Selecting the Best Approach for the Treatment of Multiple Non-Metastatic Hepatocellular Carcinoma

SIMPLE SUMMARY: The best therapy for patients with multiple HCC within the Milan Criteria is liver transplantation (LT). However, LT cannot be offered to all the patients. For the intermediate staged multiple HCC trans-arterial chemoembolization (TACE) still remains the treatment of choice. However, a growing body of evidence is showing better outcomes after surgery than TACE. Trans-arterial radioembolization and stereotaxic body radiation therapy can also play an important role in this setting. Furthermore, the role of minimally invasive liver surgery (MILS) for patients with multiple HCC is still debated. ABSTRACT: According to the Barcelona Clinic Liver Cancer (BCLC) staging system, the optimal strategy for patients with multiple HCC within the Milan Criteria is liver transplantation (LT). However, LT cannot be offered to all the patients due to organ shortages and long waiting lists, as well as because of the advanced disease carrying a high risk of poor outcomes. For early stages, liver resection (LR) or thermal ablation (TA) can be proposed, while trans-arterial chemoembolization (TACE) still remains the treatment of choice for intermediate stages (BCLC-B). Asian guidelines and the National Comprehensive Cancer Network suggest LR for resectable multinodular HCCs, even beyond Milan criteria. In this scenario, a growing body of evidence shows better outcomes after surgical resection when compared with TACE. Trans-arterial radioembolization (TARE) and stereotaxic body radiation therapy (SBRT) can also play an important role in this setting. Furthermore, the role of minimally invasive liver surgery (MILS) specifically for patients with multiple HCC is still not clear. This review aims to summarize current knowledge about the best therapeutical strategy for multiple HCC while focusing on the role of minimally invasive surgery and on the most attractive future perspectives.