Tumor burden score (TBS) has been recently introduced to indicate the extent of tumor burden in different cancers, but its role in advanced hepatocellular carcinoma (HCC) is unclear. We aimed to determine the prognostic role of TBS in patients with HCC beyond the Milan criteria receiving surgical resection (SR) or transarterial chemoembolization (TACE). A total of 1303 newly diagnosed HCC patients beyond Milan criteria receiving SR or TACE as the primary therapy were retrospectively analyzed. Independent prognostic predictors were examined by the multivariate Cox proportional hazards model. SR was associated with better overall survival compared with TACE in these patients. Multivariate Cox analysis of the entire cohort revealed that age > 66 years (hazard ratio [HR]: 1.145, 95% confidence interval [CI]: 1.004-1.305, p = 0.043), serum α-fetoprotein > 200 ng/mL (HR: 1.602, 95% CI: 1.402-1.831, p < 0.001), performance status 2-4 (HR: 1.316, 95% CI: 1.115-1.553, p < 0.001), medium TBS (HR: 1.225, 95% CI:1.045-1.436, p = 0.012), high TBS (HR: 1.976, 95% CI: 1.637-2.384, p < 0.001), albumin-bilirubin (ALBI) grade 2-3 (HR: 1.529, 95% CI: 1.342-1.743, p < 0.001), presence of vascular invasion (HR: 1.568, 95% CI: 1.354-1.816, p < 0.001), and TACE (HR: 2.396, 95% CI: 2.082-2.759, p < 0.001) were linked with decreased survival. SR consistently predicted a significantly better survival in different TBS subgroups. TBS is a feasible and independent prognostic predictor in HCC beyond the Milan criteria. SR provides better long-term outcome compared with TACE in these patients independent of TBS grade, and should be considered as the primary treatment modality in this special patient group.
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