Preoperative liquid biopsy for optimal patient selection in metastatic colorectal cancer

In this pilot study, we sought to determine if preoperative circulating tumor DNA could be a useful predictor to avoid futile metastasectomy, predict early postoperative recurrence, and determine optimal chemotherapy duration during the management of patients with resectable metastatic colorectal cancer.

Patients from 2021 to 2023 were enrolled prospectively and evaluated with circulating tumor DNA preoperatively and postoperatively for detection of recurrence. Clinicopathologic and treatment factors as well as disease-free survival were compared between those with undetectable versus detectable preoperative circulating tumor DNA.

Twenty-eight patients were evaluated, with a median follow-up time of 24 months. The median preoperative circulating tumor DNA level was 0.16 MTM/mL [0.00, 2.30]. Of the 10 patients (40%) with a preoperative circulating tumor DNA level of zero, 5 patients (50%) recurred between 4 and 18 months postoperatively. Among the 18 patients whose disease recurred, 10 patients (56%) had circulating tumor DNA detected postoperatively. Median change between preoperative and postoperative circulating tumor DNA levels was 0.00 [-0.02, 0.05] in those who did not recur and 0.00 [-7.04, 0.00] in those who recurred. When disease-free survival was evaluated by detectable versus undetectable preoperative circulating tumor DNA levels, there was no difference in disease-free survival estimates (P value = .11). On univariate Cox proportional hazards analysis, the preoperative circulating tumor DNA level, change between preoperative and postoperative circulating tumor DNA levels, and postoperative circulating tumor DNA levels did not influence disease-free survival. However, those with detectable postoperative circulating tumor DNA were 3.96 (95% confidence interval 1.30-12.06) times as likely to recur compared to those with undetectable postoperative circulating tumor DNA.

New technologies including use of circulating tumor DNA may help better predict which patients with colorectal liver metastases will undergo futile surgery. Our preliminary findings suggest that postoperative, and not preoperative, circulating tumor DNA is predictive of recurrence following metastasectomy. Use of circulating tumor DNA in guiding operative management should be done in conjunction with high-quality imaging and other serologic markers to determine which patients with colorectal liver metastases are likely to receive durable benefit from operative intervention.