Supplementary Material for: Prognosis of hepatectomy versus systemic chemotherapy based on oncological resectability criteria for borderline resectable hepatocellular carcinoma

Introduction: Oncological resectability criteria for hepatocellular carcinoma have been defined (resectable [R]/borderline resectable 1 [BR1]/borderline resectable 2 [BR2]); however, their validation is necessary. Methods: A total of 1469 patients who underwent hepatectomy and 525 patients who received systemic chemotherapy, including lenvatinib, atezolizumab plus bevacizumab, and durvalumab plus tremelimumab, as first-line treatment were analyzed. Results: In the BR1 group, the median survival times (MSTs) of patients who underwent hepatectomy and systemic chemotherapy were 52.7 and 34.6 months, respectively, without a significant difference (p=0.075). In the propensity score matching (PSM) analysis of the BR1 group, the MSTs of hepatectomy and systemic chemotherapy were 42.4 and 35.1 months, respectively, without a significant difference (p=0.772). Hepatitis virus infection, modified albumin-bilirubin (mALBI) grade 2b+3, and the presence of extrahepatic metastasis were identified as poor prognostic factors for hepatectomy, whereas mALBI grade 2b+3 was the only poor prognostic factor for systemic chemotherapy. In the BR2 group, the MSTs of hepatectomy and systemic chemotherapy were 20.1 and 19.5 months, respectively, with significantly better survival for hepatectomy than for systemic chemotherapy (p=0.017). In the PSM analysis of the BR2 group, the MSTs of hepatectomy and systemic chemotherapy were 20.1 and 21.0 months, respectively, without a significant difference (p=0.375). Serum alpha-fetoprotein levels≥100, intrahepatic tumor number ≥6, and the presence of extrahepatic metastasis were identified as poor prognostic factors for hepatectomy, whereas female, serum alpha-fetoprotein levels≥100, mALBI grade 2b+3, intrahepatic maximal tumor size>5 cm, and the presence of extrahepatic metastasis were identified as poor prognostic factors for systemic chemotherapy. Conclusion: In the PSM analysis, no significant differences were observed between the BR1 and BR2 groups for hepatectomy and systemic chemotherapy. The intrahepatic tumor number for hepatectomy and the intrahepatic maximal tumor size for systemic chemotherapy are significant risk factors for BR2 patients, highlighting the characteristics of each treatment and the potential for selecting the optimal modality.