Longitudinal surveillance of three biomarkers to predict recurrence of hepatocellular carcinoma after radical resection

Abstract Background: Radical resection is a curative treatment for patients with hepatocellular carcinoma (HCC), but the incidence of recurrence remains high. We aimed to explore the performance of predicting HCC recurrence by longitudinal surveillance of the protein induced by vitamin K absence (PIVKA-II), alpha-fetoprotein (AFP), and lectin-reactive AFP (AFP-L3) during postoperative follow-up. Methods: Patients who underwent radical resection for HCC at the Ningbo Medical Centre Lihuili Hospital between January 2015 and December 2020 were included. All enrolled patients regularly monitor PIVKA-Ⅱ, AFP, AFP-L3 every 3 months during postoperative follow-up. The surveillance performance of PIVKA-Ⅱ, AFP, AFP-L3 during follow-up for the prediction of HCC recurrence was compared in patients. The Generalized Estimation Equation (GEE) was used to analyze the trends of the tumor biomarkers and interactions with time. Area under the receiver operator characteristic (AUROC) curves, the optimal cut-off value, the sensitivity and specificity were calculated to evaluate the performance of the three biomarkers. The recurrence-free survival (RFS) of patients with any of the elevated biomarkers was analyzed by Kaplan-Meier curves and the log-rank test. Results: The GEE analysis indicated that PIVKA-II, AFP, AFP-L3 in the recurrence patients were higher than the no recurrence patients during follow-up, PIVKA-Ⅱ and AFP showed increasing trends from 6 months before recurrence. In predicting recurrence, the AUROCs for PIVKA-Ⅱ, AFP, AFP-L3 and their combination were 0.885, 0.754, 0.781 and 0.885 respectively, the optimal cut-off value for PIVKA-Ⅱ, AFP, AFP-L3 was 29.5 mAU/ml, 10.7 ng/L, 1.5 % respectively. The sensitivity in predicting recurrence for PIVKA-Ⅱ, AFP, AFP-L3 and combination were 75.0%, 54.7%, 57.8% and 79.7% respectively. The RFS of patients with any of the biomarkers elevated during the follow-up was significantly shorter than that without elevated biomarkers (χ2=62.125, P<0.001).Conclusion: Longitudinal surveillance of PIVKA-II, AFP and AFP-L3 can effectively predict recurrence of HCC after operation.