Development of a Prognostic Predictive Model for Barcelona Clinic Liver Cancer Stage C Hepatocellular Carcinoma Receiving First-line Targeted Therapy plus Immunotherapy

<title>Abstract</title> <p>Objective To develop a prognostic model for patients with hepatocellular carcinoma (HCC) classified under Barcelona Clinic Liver Cancer (BCLC) stage C receiving first-line targeted therapy plus immunotherapy, and to evaluate its performance in the study cohort. Patients and methods: We retrospectively enrolled 104 patients with BCLC stage C HCC who received first-line targeted therapy plus immunotherapy between December 2019 and June 2023. Clinical variables significantly associated with overall survival (OS) in univariable Cox regression were entered into a multivariable Cox proportional hazards model to identify independent predictors for construction of a prognostic model. Model performance was assessed using the concordance index (C-index), receiver operating characteristic (ROC) curves, and calibration curves. Patients were further stratified into three risk subgroups according to nomogram scores, and Kaplan-Meier analysis with log-rank testing was used to compare survival outcomes among subgroups. Results In the overall cohort, median OS was 14.3 months and median PFS was 6.3 months. Univariable and multivariable Cox regression analyses showed that extrahepatic metastasis (HR = 1.99, 95% CI: 1.10–3.57, P = 0.022), alkaline phosphatase &gt; 114 IU/L (HR = 2.26, 95% CI: 1.15–4.44, P = 0.018), and lactate dehydrogenase &gt; 206 U/L (HR = 2.16, 95% CI: 1.12–4.17, P = 0.021) were independently associated with worse OS, whereas locoregional therapy was independently associated with better OS (HR = 0.56, 95% CI: 0.33–0.93, P = 0.026). The prognostic model incorporating these four variables showed favorable discrimination at 1 and 2 years, with AUCs of 0.831 and 0.828, and a C-index of 0.732 (95% CI: 0.675–0.789). Based on the nomogram score, patients were classified into low-, medium-, and high-risk subgroups, with median OS of 24.0, 12.2, and 5.5 months and median PFS of 12.5, 7.8, and 3.2 months across the three subgroups (both P &lt; 0.0001). Conclusion We developed a prognostic model based on four routinely available clinical variables for patients with BCLC stage C HCC receiving first-line targeted therapy plus immunotherapy. We also established an online calculator based on this model. In this retrospective single-center cohort, the model showed good predictive performance in individualized prognostic evaluation. Further validation in larger independent cohorts is needed.</p>