Clinical usefulness of double biomarkers AFP and PIVKA-II for subdividing prognostic groups in locally advanced hepatocellular carcinoma

Background & Aims: In this study, we investigated the clinical usefulness of AFP and PIVKA-II in subdividing prognostic groups in patients with locally advanced HCC treated locally. Methods: Patients who had undergone local treatment for locally advanced HCC between 2001 and 2006 were enrolled. Response to treatment was defined as a reduction in AFP or PIVKA-II by more than 50% from baseline levels at 1 month after the treatment completion. Patients were divided according to their AFP and PIVKA-II response: A↓P↓ [AFP response (+) and PIVKA-II response (+)]; A↓P↑ [AFP response (+) and PIVKA-II response (-)]; A↑P↓ [AFP response (-) and PIVKA-II response (+)]; A↑P↑ [AFP response (-) and PIVKA-II response (-)]. Clinical characteristics and prognosis were compared between groups. Results: Patients were subdivided into four groups by the change in the level of the biomarkers AFP and PIVKA-II, and the survival outcomes of each group were distinct. Among patients with an AFP response, further subdivision by PIVKA-II response revealed that those in the A↓P↓ group had a longer median progression-free survival (PFS) and overall survival (OS) compared with those in the A↓P↑ group (PFS: 16.2 vs. 5.1 months, P = 0.009; OS: 26.3 vs. 7.3 months, P = 0.017). Combination of AFP and PIVKA-II response showed a predictive power for PFS and OS comparable to radiological criteria and better than AFP response alone. Conclusions: In patients with locally advanced HCC, the use of a combination of two biomarkers, AFP and PIVKA-II, appears useful in predicting treatment outcomes through the subdivision of prognostic groups.