Prognostic value of the αPRTA scoring system in unresectable hepatocellular carcinoma treated with TACE, Lenvatinib, and anti-PD-1 antibodies: a multicenter retrospective study

Background and aims This study is designed to develop a prognostic scoring model for identifying unresectable hepatocellular carcinoma (uHCC) patients who are likely to get clinical benefit from transcatheter arterial chemoembolization (TACE) combined with lenvatinib and anti-programmed death-1 (anti-PD-1) antibodies (triple therapy). By doing so, we aim to address the problem that the significant efficacy heterogeneity and the paucity of valid biomarkers which currently exists in combination treatment strategies. Methods Univariate and multivariate Cox regression analyses were used to identify key factors influencing the prognosis of patients with uHCC who underwent triple therapy. Survival differences were analyzed using Kaplan-Meier curves, and using the area under the receiver operating characteristic curve (AUC) to evaluate the predictive performance of the model. Evaluate the safety of the treatment by using the incidence and severity of adverse events. Results This study retrospectively evaluated 210 uHCC patients from three medical centers in China who received triple therapy from October 2019 to December 2024. According to the inclusion and exclusion criteria, 149 uHCC patients were enrolled. The patients were divided into training (n = 90) and external validation (n = 59) cohorts. In the training cohort, multivariate analysis identified three independent predictors of poor survival: α-hydroxybutyrate dehydrogenase (α-HBDH) to prealbumin (αPR) > 1.21, maximum tumor diameter > 7 cm, and ALBI grade > -2.4, based on which the αPRTA scoring system was established. According to the scores, uHCC patients who underwent triple therapy were divided into three distinct prognostic groups: favorable (αPRTA score ≤ 0.90), intermediate (0.90 < score ≤ 1.80), and poor (score > 1.80). In the training cohort, the median overall survival (OS) was 16 months (95% confidence interval, 14.5–17.5) and the median progression-free survival (PFS) was 12 months (95% confidence interval, 9.9–14.1). The objective response rate (ORR) was 55.56% and the disease control rate (DCR) was 80.0%. These findings were confirmed in an external validation cohort. Conclusion The triple therapy shows promising potential for the treatment of uHCC. The αPRTA scoring system is helpful for predicting the prognosis of patients with uHCC who received triple therapy.