Abstract
BACKGROUND: Previous studies have shown that the alpha-fetoprotein (AFP) response has been a key tumour marker in hepatocellular carcinoma (HCC), but its definition remains controversial. Recently, a new study has explored and defined the AFP serological response and used it to explain the subclass of intermediate-stage hepatocellular carcinoma (IM-HCC) with "sharp-falling" AFP change after transarterial chemoembolization (TACE). It may be a new and simple tool for assessing the prognosis of patients. This study aims to explore a simplified AFP trajectory and its impact on overall survival (OS) and disease-free survival (DFS) for IM-HCC after hepatectomy. PATIENTS AND METHODS: Between January 2007 and May 2012, data from the Sun Yat-sen University Cancer Center was examined in this longitudinal, retrospective cohort study. A generalized additive model was applied to distinguish potential AFP dynamic trajectories. The Kaplan-Meier method was applied to analyze OS and DFS, and multivariate Cox models were used to calculate adjusted hazard ratios (aHRs) and 95% CIs for overall survival. RESULTS: 144 patients who had IM-HCC with at least three AFP repeat measurements were included in the study. Three similar trajectories are displayed using the generalized additive model: low-stable (35.4%; n = 51), high-rising (36.1%; n = 52), and sharp-falling (28.5%; n = 41). Compared with the low-stable class, the aHRs for death were 2.84 (1.50, 5.41) and 0.59 (0.25, 1.40) for the high-rising and sharp-falling classes, adjusted by age and log AFP. Simplified AFP trajectory had higher relative importance than sex, intrahepatic tumor number, Child-Pugh class, and baseline AFP. CONCLUSION: The simplified AFP trajectory is a promising biomarker for IM-HCC patients undergoing hepatectomy. In the future, it should be verified by a larger population containing various stages of HCC.