Harnessing early postoperative MRD and VAF dynamics for precision prognosis in resected colorectal liver metastases

Circulating tumor DNA (ctDNA) shows promise for predicting recurrence in colorectal cancer liver metastases (CRLM) patients. We investigated the prognostic value of perioperative ctDNA, particularly 2 week postoperative minimal residual disease (MRD), in CRLM patients undergoing liver resection.

We prospectively collected blood samples from 94 CRLM patients before (after neoadjuvant therapy, if any) and 2 weeks after liver metastasectomy. 63 patients had both assessments. ctDNA status and variant allele fraction (VAF) were determined using targeted sequencing. Disease-free survival (DFS) was analyzed using Kaplan-Meier curves and Cox regression. Baseline characteristics were compared based on ctDNA status.

Preoperative ctDNA status was not associated with DFS (p = 0.77). However, postoperative 2 week MRD status was a strong predictor; MRD-positive patients (N = 31) had significantly worse DFS than MRD-negative patients (N = 32) (p < 0.001). In multivariate analysis, postoperative MRD positivity (HR = 5.52, 95% CI: 2.46-12.39, p < 0.001) and multiple metastases (HR = 3.42, 95% CI: 1.42-8.25, p = 0.006) were independent predictors of DFS. Postoperative MRD positivity showed a trend towards association with higher primary tumor T stage (p = 0.095). Among MRD-negative patients, a higher maximum absolute VAF change (MaxΔVAF) suggested potentially worse DFS (p = 0.053), while it held no prognostic value in MRD-positive patients (p = 0.99).

Postoperative 2 week ctDNA (MRD) status is a potent, independent predictor of DFS in resected CRLM patients and outperforms preoperative ctDNA. Early MRD assessment should be considered for risk stratification and may help guide adjuvant treatment decisions. VAF dynamics might further refine prognosis, especially in MRD-negative cases.