Editor's Note: Liver cancer is a highly prevalent and poorly prognosed malignancy, with a postoperative recurrence rate as high as 60%-70%. Postoperative minimal residual disease (MRD) is the main culprit behind cancer recurrence and metastasis, but currently, methods to detect MRD in liver cancer are very limited. At the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting, a prospective study reported by Dr. Jia Fan, Dr. Jian Zhou, and Dr. Xinrong Yang’s team from Zhongshan Hospital affiliated with Fudan University shows that circulating tumor DNA (ctDNA) can serve as an ideal marker for detecting postoperative MRD in liver cancer, effectively warning of recurrence and metastasis. Furthermore, ctDNA monitoring of MRD can guide postoperative adjuvant therapy decisions and monitor the efficacy of drug treatments, thereby aiding in the precise management of liver cancer throughout the postoperative period and significantly improving patient prognosis.

A prospective study was conducted between 2019 and 2021, involving 136 hepatocellular carcinoma patients who underwent radical surgery. Plasma samples were collected preoperatively, one month postoperatively, and during subsequent monitoring periods, with a median follow-up of 24 months and a total of 625 plasma samples collected. Whole-exome sequencing of tumor tissue was performed to identify specific somatic mutations, and 16 major clonal mutations were selected for ultra-deep sequencing to monitor postoperative circulating tumor DNA (ctDNA) and assess minimal residual disease (MRD).

Recurrence occurred in 45 patients (33.1%). Preoperative ctDNA concentration was significantly higher in recurrent patients (median: 125.0 MTM/mL) compared to non-recurrent patients (median: 8.4 MTM/mL, P<0.001). Most patients (80.9%) experienced a drop in ctDNA concentration to negative levels after surgery, while those with persistently positive ctDNA post-surgery had a significantly increased risk of recurrence (HR=11.5, P<0.001). Long-term monitoring revealed that a transition from negative to positive ctDNA indicated a higher risk of recurrence (HR=69.3, P<0.001). The area under the curve (AUC) for long-term ctDNA monitoring as a predictor of recurrence was 0.956, with a sensitivity of 93.3% and specificity of 97.8%. The median interval from the first positive ctDNA detection to imaging-confirmed recurrence was 4.0 months. ctDNA monitoring outperformed alpha-fetoprotein in predicting recurrence (AUC=0.956 vs. 0.680, P<0.001). Patients with positive ctDNA benefited from postoperative adjuvant therapy (HR=0.4, P=0.019), and a decrease or stabilization in ctDNA levels post-therapy indicated effective treatment and significantly delayed postoperative recurrence (HR=0.3, P<0.001).

This study confirms ctDNA as a reliable indicator for detecting postoperative MRD in liver cancer, capable of warning of recurrence before imaging confirmation. ctDNA also plays a crucial role in guiding postoperative adjuvant therapy and evaluating treatment efficacy, enabling refined management of postoperative liver cancer patients, supporting precise treatment, and improving overall patient prognosis.