Higher Hepatocellular Carcinoma Tumor Burden Score Is Associated with Worse Outcomes in Patients Listed for Liver Transplantation due to Higher Waitlist Dropout Rates

Introduction: Liver transplantation (LT) is the best treatment for early-stage hepatocellular carcinoma (HCC) patients with cirrhosis. However, patients with different tumor burdens receive the same listing priority. We hypothesized that patients listed for LT but with higher tumor burden scores (TBS) have a higher risk for waitlist (WL) dropout. Methods: We performed a retrospective study using the Scientific Registry of Transplant Recipient (SRTR) database. TBS was defined as the hypotenuse of the maximum tumor size and the number of tumors. We used Kaplan-Meier analysis and Cox Proportional Hazards Ratio model for statistical analysis. Results: This analysis included 36,555 HCC patients listed between 2002 and 2019, with 24,391 patients transplanted. In univariate analysis, High-TBS patients had 83% higher risk for WL dropout, with only 27% and 31% higher risk for death with and without LT, respectively. If transplanted, high-TBS patients achieved higher absolute survival rate benefits. In multivariate analysis, high-TBS patients had a 92% higher risk for dropout, with only 26% and 46% higher risk for death with and without LT, respectively. If transplanted, the survival hazards benefit is higher in high-TBS patients compared to low-TBS patients (interaction-HR 0.634 [0.553-0.726], p<0.001). Conclusion: When listed, patients with higher HCC TBS at presentation had a higher risk of death with or without transplantation. However, if transplanted, they achieved greater survival benefits than patients with lower TBS. The main risk for patients with higher TBS was due to significant WL dropout rates. Differential priority should be considered for patients with different TBS.