Sorafenib has been recommended as the standard therapy for advanced HCC with extrahepatic metastasis. The purpose of this retrospective study was to investigate the difference in overall survival (OS) between treatments with sorafenib combined with regional therapies versus sorafenib monotherapy in hepatocellular carcinoma (HCC) patients with pulmonary oligometastases. The study retrospectively enrolled 95 consecutive patients who underwent sorafenib therapy. A combined group (CG) of 40 patients received regional therapy in addition to sorafenib, and a monotherapy group (MG) of 55 patients received only sorafenib. OS was the primary endpoint, and time to progression (TTP) was the secondary endpoint. Subgroup analysis was further performed to evaluate the differences between the two groups. A propensity score-matched analysis was performed to overcome the bias. Median OS was significantly longer in the CG than in the MG (18.37 vs. 7.13 months; = 0.002). Multivariate analysis identified three baseline characteristics that were prognostic indicators of OS: macrovascular invasion, regional therapy, and alpha-fetoprotein. Median TTP was significantly longer in the CG than in the MG (2.93 vs. 2.23 months; = 0.004). Further multivariate analysis showed alpha-fetoprotein, total bilirubin, and regional therapy as prognostic indicators of TTP. After propensity score matching, 34 paired patients constituted each group. Patients in the adjusted CG showed a longer OS and TTP than those in the adjusted MG (OS: 18.37 vs. 7.37 months, = 0.015; TTP: 3.12 vs. 2.265 months, = 0.009). Multivariate analysis showed that combining regional therapies was still a prognostic indicator of OS ( = 0.01) and TTP ( = 0.001). Sorafenib combined with regional therapies may be associated with prolonged OS and TTP in HCC patients with pulmonary oligometastases compared with sorafenib monotherapy.

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