Takeshi Yokoo, Amish D Patel, Naama Lev-Cohain, Amit G Singal, Adam C Yopp, Ivan Pedrosa

Extrahepatic metastases have important implications in the clinical management of hepatocellular carcinoma (HCC). The purpose of this study was to validate tumor staging parameters and serum AFP as risk factors of HCC metastasis. In this retrospective case-control study, patients with a new diagnosis of HCC (N=236), median age 57 years (range 28-89 years), and male-to-female ratio of 183/53 were divided into a "no-met" group (N=101) without extrahepatic metastasis or a "met" group with extrahepatic metastases (N=135). Metastasis risk factors based on tumor staging parameters (size, number, infiltration, and vascular invasion) and serum AFP level were calculated as odds ratio (OR). Sensitivities of the risk factors as metastasis screening tests were also calculated. AFP >400 μg/mL, index tumor size >5 cm, and vascular invasion individually had strong association with metastasis, with OR (95% confidence interval) of 11.5 (5.9-22.1), 17.7 (9.0-34.8), and 18.9 (8.2-43.9), respectively, but with moderate sensitivities as metastasis screening tests, with 71.9% (65.7-77.3), 75.6% (69.6-80.7), and 58.5% (52.1-64.7), respectively. Composite multiparametric criteria, eg, a logical union of 1) tumor size outside of Milan criteria, 2) AFP threshold >35 μg/mL, and 3) vascular invasion, had excellent OR up to 55.6 (13.0-237.1) with screening sensitivity 98.5% (95.8-99.6). Serum AFP, tumor size, and vascular invasion are strongly associated with extrahepatic metastasis of HCC, especially when combined into a multiparametric metastasis prediction criterion.