Advances in systemic therapy leading to conversion surgery for advanced hepatocellular carcinoma

Recently, a systemic therapy for advanced hepatocellular carcinoma (HCC) has been developed. The regimen for unresectable HCC varies and includes single or multi-tyrosine kinase inhibitors, monoclonal antibodies, immune checkpoint inhibitors, or their combinations. Treatment with these agents begins with sorafenib as the first-line drug for unresectable HCC. Subsequently, several systemic therapies, including lenvatinib, ramucirumab, cabozantinib, and regorafenib have been investigated and established. With advances in systemic therapy for unresectable HCC, the prognosis of patients with unresectable HCC has improved significantly than previously. Conversion surgery, consisting of systemic therapy and surgery, showed the possibility of improving the prognosis than systemic therapy alone. Although a combination of atezolizumab and bevacizumab is mostly used for initially unresectable HCC to conduct conversion surgery because of the high response rate and fewer adverse events compared to others, many trials are being conducted to assess their efficacy for initially unresectable HCC. However, the appropriate timing of surgery and interval between systemic therapy and surgery remain controversial. To address these issues, a multidisciplinary team can play a vital role in determining the strategies for treating unresectable HCC. This review describes previous and current trends in the treatment of HCC, with a particular focus on conversion surgery for initially unresectable HCC.