Prognostic Value of Postoperative Circulating Tumor DNA in Patients With Early- and Intermediate-Stage Hepatocellular Carcinoma

Majority of patients with resected early- and intermediate-stage liver cancer will experience postoperative recurrence. This study aimed to investigate the application of ctDNA sequencing in the postoperative period of hepatocellular carcinoma. A total of 96 patients with liver cancer were enrolled in this study. Postoperative peripheral blood samples were collected from all patients after surgery and analyzed using hybridization capture-based next-generation sequencing. Identification of at least one somatic mutation in the peripheral blood was defined as ctDNA+. Five genetic features in tumor tissues were associated with disease-free survival (DFS) using Lasso-Cox model. The area under the receiver operating characteristic curve was 0.813 and 0.882 in training and validation cohorts, respectively. The recurrence rate in ctDNA+ and ctDNA- groups was 60.9% and 27.8%, respectively. Multivariate Cox regression analysis showed that the postoperative ctDNA was an independent prognostic predictor of DFS (HR [hazard ratio]: 6.074, 95% Cl [confidence interval]: 2.648-13.929, P<0.001) and overall survival (OS) (HR: 4.829, 95% CI: 1.508-15.466, P=0.008). Combined ctDNA with AFP improved prediction performance. The median DFS was 2.0, and 8.0 months in ctDNA+/AFP-H and ctDNA+/AFP-L groups, respectively; while ctDNA-/AFP-H and ctDNA-/AFP-L groups had not reached the median time statistically (Log-rank test, P < 0.0001). Furthermore, ctDNA- patients had better prognosis than ctDNA+ patients irrespective of tumor stage. Postoperative ctDNA sequencing has great prognostic value in patients with liver cancer. Patients with positive ctDNA should receive more intensive disease monitoring and more aggressive treatment strategies to improve the survival time.