Background: There is little evidence concerning survival after surgery in patients with hepatocellular carcinoma who have received lenvatinib treatment. The aim of this study was to evaluate whether post-lenvatinib surgical treatment in patients with hepatocellular carcinoma improves overall survival. Methods: The cohort of this retrospective study comprised 55 patients with hepatocellular carcinoma who had undergone lenvatinib treatment. We classified them into two groups according to post-lenvatinib surgical treatment status and compared clinicopathologic factors and prognosis between the two groups with the aim of identifying predictors of overall survival. Results: The median duration of lenvatinib administration was 5.8 months (range, 0.4–24.0 months). Twelve of the 55 patients underwent surgery after receiving lenvatinib. There was no significant difference in assessed clinicopathological factors between patients who did and did not undergo surgery after being treated with lenvatinib. Multivariate analysis revealed that older age was associated with a significantly worse overall survival (hazard ratio: 2.332; 95% confidence interval 1.062–5.168; P = 0.0369) and that surgery after treatment with lenvatinib achieved better overall survival than other forms of treatment (hazard ratio: 0.121; 95% confidence interval 0.016–0.901; P = 0.0393). Conclusions: Surgical treatment after lenvatinib administration may be a useful therapeutic option for select patients with hepatocellular carcinoma.
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