Tumor recurrence rate after surgery or ablation of hepatocellular carcinoma (HCC) is as high as 70%. However, there are no widely accepted adjuvant therapies; therefore, no treatment has been recommended by guidelines from the American Association for the Study of Liver Disease or the European Association for the Study of the Liver. All the registered trials failed to find any treatment to prolong recurrence-free survival, which is the primary outcome in most studies, including sorafenib. Some investigator-initiated studies revealed that anti-hepatitis B virus agents, interferon-α, transcatheter chemoembolization, chemokine-induced killer cells, and other treatments prolonged patient recurrence-free survival or overall survival after curative therapies. In this review, we summarize the current status of adjuvant treatments for HCC and explain the challenges associated with designing a clinical trial for adjuvant therapy. Promising new treatments being used as adjuvant therapy, especially anti-PD-1 antibodies, are also discussed.

Liver cancer, mostly hepatocellular carcinoma (HCC), is the second leading cause of cancer mortality globally. Most patients were diagnosed at an advanced stage, and systemic therapy is the standard of care. All the approved systemic therapies for HCC are molecular targeted therapies with anti-angiogenic effects targeting the vascular endothelial growth factor signaling pathway. Sorafenib and lenvatinib are the first-line treatment, and regorafenib, ramucirumab, and cabozantinib are second-line treatment options. Although anti-PD-1 antibodies, including nivolumab and pembrolizumab, demonstrated promising anti-tumor effects as monotherapy for advanced HCC in phase II clinical trials, both failed in phase III studies. Anti-angiogenic treatment remains the backbone of systemic therapy for HCC. In this review, we summarized the approved anti-angiogenic medicines and discussed the potential strategies to improve the efficacy of anti-angiogenic therapy, including combination therapy with other treatments, and discussed the approaches to overcome the drawbacks of anti-angiogenic therapies.