A simple ABC score for prognosis stratification and treatment selection in advanced hepatocellular carcinoma.

511 Background: Atezolizumab plus bevacizumab (A+B) is widely used as a standard first-line therapy for advanced hepatocellular carcinoma (HCC), while lenvatinib (L) and lenvatinib plus immunotherapy (L+I) remain common alternatives in clinical practice. Some patients have poor responses to A+B, and predictive biomarkers are lacking. We aimed to develop a simple blood-based prognostic score to aid in prognosis stratification and clinical decision-making. Methods: This retrospective international study included HCC patients treated with A+B, L, or L+I at 11 hospitals in Japan and 15 hospitals in Taiwan. Cox regression analysis was used to identify key prognostic factors for overall survival (OS). Results: Between September 2017 and March 2024, 1442 HCC patients were included, with a median age of 67.9 years and 77.7% being male. Multivariable analysis identified three independent poor prognostic factors, which were integrated into the ABC score: baseline (A)lpha-fetoprotein >20 ng/mL (hazard ratio [HR] 1.79; p<0.001), al(B)umin <3.5 g/dL (HR 1.71; p<0.001), and (C)hronic inflammation (neutrophil-to-lymphocyte ratio [NLR] >4; HR 1.50; p<0.001). Patients were distributed among ABC scores of 0 (242; 16.8%), 1 (551; 38.2%), 2 (483; 33.5%), and 3 (166; 11.5%), with corresponding median OS of 40.3, 22.7, 12.0, and 8.0 months, respectively (P<0.001). In the entire cohort, OS was similar across treatment regimens (median OS: 16.5 months for A+B, 20.1 months for L, and 17.7 months for L+I; P=0.087). However, among the 649 (45%) high-risk patients (ABC score 2–3), those treated with lenvatinib-based therapies had significantly better OS (median OS: 8.4 months for A+B, 11.0 months for L, and 13.7 months for L+I; P=0.0039). Conclusions: The ABC score is a simple and robust tool associated with survival in patients receiving first-line A+B or lenvatinib-based therapy. It may facilitate prognosis stratification and help clinical decision-making, but requires prospective validation. Multivariable Cox regression for overall survival. Variables HR 95% CI p-value Age 1.01 1.00–1.02 0.008 Sex (male vs. female) 0.87 0.73–1.03 0.106 ECOG Performance Status 0 — — — 1 1.35 1.15–1.59 <0.001 ≥2 1.89 1.46–2.44 <0.001 Vascular invasion (Yes vs. No) 1.50 1.27–1.76 <0.001 Extrahepatic spread (Yes vs. No) 1.21 1.04–1.41 0.014 AFP≥20 ng/ml (Yes vs. No) 1.79 1.52–2.11 <0.001 Albumin ≤ 3.5 g/dL (Yes vs. No) 1.71 1.46–1.99 <0.001 NLR≥4 (Yes vs. No) 1.50 1.29–1.75 <0.001 First-line treatment Lenvatinib + Immunotherapy — — — Lenvatinib monotherapy 0.83 0.66–1.03 0.090 Atezolizumab + bevacizumab 1.14 0.89–1.45 0.301 ECOG Performance Status: Eastern Cooperative Oncology Group Performance Status; AFP: alpha-fetoprotein; NLR: neutrop