Dynamic CtDNA monitoring in adjuvant therapy and recurrence for colorectal liver metastases (PKUCRLM-01): a prospective study.

Introduction: Effective prediction methods for monitoring the risk of recurrence of colorectal cancer liver metastasis (CRLM) and guiding postoperative adjuvant treatment (ACT) are currently lacking. This study aimed to evaluate the value of postoperative dynamic circulating tumor DNA (ctDNA) monitoring in guiding ACT and predicting recurrence compared with other clinicopathological factors.

Methods: This prospective study enrolled 414 consecutive patients with CRLM who underwent radical resection. Regular dynamic ctDNA monitoring was performed every 3 months until 1 year postoperatively or on clinical recurrence. ctDNA detection was performed using the J25 detection panel, previously constructed and verified at our center.

Results: Postoperative ctDNA status at 1 month [hazard ratio (HR) = 3.64, 95% confidence interval (CI) 2.37-5.59, P <0.0001] significantly distinguished long-term survival. ctDNA-positive patients (HR = 0.228, 95% CI 0.116-0.446, P <0.0001) benefitted more from ACT than ctDNA-negative patients ( P = 0.39). Dynamic assessment of ctDNA status at 1 and 3-6 months postoperatively showed a significantly better prognosis in patients who remained negative or converted to negative than in those who remained positive (HR = 11.20, 95% CI 3.90-32.22, P <0.0001) or negative turned positive (HR = 3.61, 95% CI 1.31-9.98, P = 0.023). ctDNA status post-ACT and 1-month post-surgery exhibited higher area under the receiver operating characteristic (AUROC = 0.73 and 0.71) for recurrence-free survival than that of postoperative carcinoembryonic antigen (AUROC = 0.53) or pathological tumor regression grade (AUROC = 0.55).

Conclusion: The J25 panel showed good performance for dynamic monitoring of ctDNA levels after radical resection of CRLM, improving static prognosis prediction, dynamic recurrence monitoring, and further guidance on ACT and early recurrence intervention.