Sorafenib therapy for hepatocellular carcinoma with extrahepatic spread: Treatment outcome and prognostic factors

Background & Aims Sorafenib is recommended as the treatment of choice for hepatocellular carcinoma (HCC) with extrahepatic spread (EHS). However, early discontinuation of sorafenib treatment is not uncommon because of adverse events, deterioration of liver function and/or performance. This study aimed to investigate the treatment outcome and prognostic factors of sorafenib treatment in HCC patients with EHS in which sorafenib was administered for at least 8 weeks. Methods From May 2007 to December 2012, a total of 254 HCC patients with EHS were treated with sorafenib monotherapy for at least 8 weeks. The treatment outcome, risk factors for disease progression, and overall survival were retrospectively analyzed. Results The median duration of radiologic progression and overall survival after sorafenib was 2.5 and 9.6 months, respectively. Prognostic factors for radiologic progression were intrahepatic tumor with macrovascular invasion (MVI) (hazard ratio (HR) 2.38, p <0.001), intrahepatic tumor without MVI (HR 2.37, p <0.001), age <60 years (HR 1.44, p = 0.008), peritoneal involvement (HR 1.57, p = 0.03), and underlying hepatitis B (HR 1.46, p = 0.05). Prognostic factors for overall survival were lack of disease control with sorafenib (HR 2.98, p <0.001), intrahepatic tumor with MVI (HR 2.23, p <0.001), intrahepatic tumor without MVI (HR 1.70, p = 0.003), Child-Pugh class B (HR 1.90, p = 0.009), serum AFP ≥200 ng/ml (HR 1.45, p = 0.009), and ALT ≥40 U/L (HR 1.34, p = 0.041). In patients with chronic hepatitis B, the use of antiviral treatment was associated with favorable overall survival after sorafenib therapy (HR 0.64, p = 0.003). Conclusion Sorafenib prolonged survival in HCC patients with EHS who achieved disease control. Intrahepatic tumor is a poor prognostic factor for both disease progression and overall survival in HCC patients with EHS treated with sorafenib.