Tumor biology characteristics score based on alpha-fetoprotein and protein induced by vitamin K absence or antagonist II as a predictor for recurrence and survival after curative resection for hepatocellular carcinoma: a multicenter cohort study

Background: Current hepatocellular carcinoma (HCC) staging systems lack comprehensive assessment of tumor biologic characteristics. This study aimed to develop and validate a tumor biology characteristics score (TBCS) based on alpha-fetoprotein (AFP) and protein induced by vitamin K absence or antagonist II (PIVKA-II) to predict long-term oncologic outcomes after HCC resection. Methods: In this multicenter retrospective cohort study, patients who underwent curative resection for HCC between June 2018 and December 2022 were included. TBCS (range, 2–6 points) was calculated by combining preoperative AFP (<20, 20–199, and ≥200 ng/mL) and PIVKA-II levels (<40, 40–399, and ≥400 mAU/mL). Patients were stratified into low (2 points), medium (3–4 points), and high TBCS groups (5–6 points). The primary outcomes were recurrence-free survival (RFS) and overall survival (OS). Results: A total of 695 patients were analyzed; the low, medium, and high TBCS groups comprised 132 (19.0%), 233 (33.5%), and 330 patients (47.5%), respectively. Notably, 5-year RFS was 30.4%, 14.7%, and 9.7%, whereas 5-year OS was 42.1%, 35.5%, and 23.5% for low, medium, and high TBCS groups, respectively (both P <.001). Multivariate analysis identified TBCS as an independent predictor of both RFS (medium TBCS: hazard ratio [HR], 1.583; 95% CI, 1.219–2.057; P =.001; high TBCS: HR, 1.895; 95% CI, 1.473–2.438; P <.001) and OS (high TBCS: HR, 1.781; 95% CI, 1.353–2.343; P <.001). Conclusion: The novel TBCS combining AFP and PIVKA-II effectively stratified patients with HCC into distinct prognostic groups after curative-intent resection, independently predicting both RFS and OS. This score may help identify high-risk patients for more intense postoperative recurrence surveillance and receipt of adjuvant therapies.