The evolution of risk factors and recurrence pattern over time in hepatocellular carcinoma after local curative treatment

Abstract Background The influence of risk factors on hepatocellular carcinoma (HCC) intrahepatic recurrence may be alterable over time. Objective To explore the evolution of risk factors and its correlation with recurrence pattern over time. Methods The information and treatment method of patients underwent laparoscopic hepatectomy (LH) or microwave ablation (MWA) with single 3-5cm HCC were collected to identify risk factors by Cox proportional hazard model. Then, Landmark test was used to analyze the evolution of factor influences from 6th to 36th months. Intrahepatic recurrence was classified into three types: local tumor progression + surgical margin recurrence (LTP + SMR), proximal intrahepatic recurrence (PIR), and distal intrahepatic recurrence (DIR) and recorded. Results From January 2010 to October 2019, 1207 patients from 12 hospitals were included with 38.7-month median follow-up. Multivariate analysis showed: male, cirrhosis, elevated alpha-fetoprotein (AFP) and MWA were risk factors for recurrence. Landmark test and recurrence pattern record show that: the influence of AFP manifested in the first 12 months after treatment (p < 0.05), during which LTP + SMR occurs frequently (69.0%, 29/42); the influence of treatment method manifested in the first 23 months (p < 0.05), and the proportion of PIR was higher than DIR in this period (54.0% vs 34.0%); male and cirrhosis had sustained influence on recurrence (p < 0.05) throughout the follow-up period, and the proportion of PIR was comparable to DIR (48.0% vs 47.2%) when short-term factors become ineffective. Conclusion The influence of risk factors on intrahepatic recurrence could evolve over time and recurrence pattern also changed with the evolution of risk factors.