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Surgery for advanced hepatocellular carcinoma: Time to take action

Dear Editor, We appreciate Dr. Wang et al. for their comments on the paper we published in Journal of Surgical Oncology [1]. Although they concur with us that surgical resection (SR) provides better survival than transarterial chemoembolization (TACE) for patients with advanced hepatocellular carcinoma (HCC), they pointed out several potential limitations of our study which we would like to address specifically. The location of vascular invasion for HCC is awell-known prognostic predictor [2]. We further divided vascular invasion into intrahepatic and extrahepatic vascular invasion [3]. In the propensity model, the proportion of patients without vascular invasion, with intrahepatic vascular invasion, or with extrahepatic vascular invasion was not significantly different betweenpatients receivingSRorTACE.Similarly, anti-viral therapy is also linked with long-term survival [4]. For patients with hepatitis B-related HCC in the propensity model, roughly 46% of patients had received anti-viral therapy. For patients with hepatitis Crelated HCC, only about 8% of patients had received anti-viral therapy. The percentages of patients who had received anti-virals were comparable between SR and TACE group. The status of vascular invasion and anti-viral therapy are well balanced in the propensity model and therefore are less likely significant confounders in our study. Sorafenib is the recommended therapy for advancedHCC[5], andwas reimbursed in Taiwan since 2012. Therefore, only a small proportion of our patients received sorafenib therapy. In our study, 14% and 10% of patients had received sorafenib aiming for better tumor control after SR and TACE, respectively. Combining TACE and sorafenib may yield better survival [6]. However, only 12 patients received combination therapy in this cohort, precluding further analysis. Finally, although the degree of tumor differentiation is a prominent prognostic predictor, the data were not available in most patients undergoing TACE. Therefore, tumor differentiation cannot be incorporated in the propensity model. In conclusion, Dr. Wang et al. raise several important concerns. Their comments and the current study demonstrate the effectiveness of SR for patients with advanced HCC. Hopefully these observations can be eventually incorporated into treatment guidelines to prolong survival for HCC patients.