Will the collaboration of surgery and external radiotherapy open new avenues for hepatocellular carcinoma with portal vein thrombosis?

Portal invasion of hepatocellular carcinoma (HCC) occurs in 12.5%-40% of patients diagnosed with cancer and yields poor clinical outcomes. Since it is a common cause of inoperability, sorafenib was regarded as the standard treatment for HCC in the Barcelona Clinic of Liver Cancer guidelines. However, the median survival of the Asian population was only approximately 6 mo, and the tumor response rate was less than moderate (< 5%). Various locoregional modalities were performed, including external beam radiotherapy (EBRT), transarterial chemoembolization, hepatic arterial infusion chemotherapy, and surgery, alone or in combination. Among them, EBRT is a noninvasive method and can safely treat tumors involving the major vessels. Palliative EBRT has been commonly performed, especially in East Asian countries, where locally invasive HCC is highly prevalent. Although surgery is not commonly indicated, pioneering studies have demonstrated encouraging results in recent decades. Furthermore, the combination of neo- or adjuvant EBRT and surgery has been recently used and has significantly improved the outcomes of HCC patients, as reported in a few randomized studies. Regarding systemic modality, a combination of novel immunotherapy and vascular endothelial growth factor inhibitor showed results superior to that of sorafenib as a first-line agent. Future clinical trials investigating the combined use of these novel agents, surgery, and EBRT are expected to improve the prognosis of HCC with portal invasion.