Development and validation of a risk prediction model for patients with hepatocellular carcinoma receiving atezolizumab-bevacizumab

Background & Aims: Atezolizumab plus bevacizumab (AB) has become the standard first-line treatment for advanced hepatocellular carcinoma (HCC). However, identifying reliable prognostic biomarkers remains a critical challenge. We aimed to develop a comprehensive scoring system to predict overall survival (OS) in advanced HCC patients receiving first-line AB. Approach & Results: We included patients with advanced HCC receiving first-line AB from multiple centers in Korea, forming a derivation cohort ( n =456) and a validation cohort ( n =205). Multivariable analysis identified five independent prognostic factors: C-reactive protein ≥1.0 mg/dL (hazard ratio [HR] 2.07; p <0.001), albumin <3.5 g/dL (HR 1.60; p =0.002), protein induced by vitamin K absence or antagonist-II ≥1,500 mAU/mL (HR 1.60; p =0.002), total bilirubin ≥1.0 mg/dL (HR 1.50; p =0.006), and macrovascular invasion (HR 1.49; p =0.009). We developed the CRAPT-M model named after these factors’ initial letters. Patients were categorized into low (≤4), intermediate (5-12), and high (≥13) risk groups by CRAPT-M score. Median OS differed significantly: 22.4 (95% CI, 18.6-25.0), 12.9 (95% CI, 8.7-14.8), and 6.7 (95% CI, 5.1-7.7) months for low-, intermediate-, and high-risk groups, respectively ( p <0.001). Time-dependent area under the receiver operating characteristic for CRAPT-M demonstrated consistently higher predictive accuracy than the CRAFITY model, with values of 0.785, 0.737, and 0.742 at 12, 24, and 36 months, respectively. The model demonstrated robust predictive performance in external validation cohort, with excellent calibration and consistent discrimination across sensitivity analyses. Conclusions: The CRAPT-M model demonstrated robust OS prediction, offering a valuable tool for prognosis estimation and clinical decision-making in advanced HCC patients receiving AB.