The prognostic role of post-operative cfDNA after resection of colorectal liver metastases: A systematic review and meta-analysis

Background Post-resection detection of cell-free DNA (cfDNA) is strongly prognostic of recurrence for patients with localized colorectal cancer (CRC). The sensitivity and specificity of this biomarker in the setting of CRC liver metastases (CRCLM) have not yet been systematically quantified. Methods PubMed was queried from database inception to June 2, 2023 for English-language publications reporting post-operative cfDNA status and recurrence-free survival (RFS) in patients with resected CRCLM. Weighted mean cfDNA positivity rates and RFS probabilities were utilized to estimate the sensitivity and specificity for recurrence at 1, 3 and 5 years after surgery. Recurrence risk using hazard ratios (HRs) and 95% CIs were calculated using a random-effects model and the DerSimonian-Laird method. Results Of 98 records, 10 studies (all non-randomized) were eligible, inclusive of 669 patients. The median weighted follow-up from surgical resection was 30.6 months (range 9.7–77.0 months). The mean postoperative cfDNA positivity rate was 38.5%, and cfDNA status was prognostic of RFS in 10 of 10 (100%) studies with a pooled HR of 3.11 (95% CI 2.29–4.22). Among cfDNA-positive patients, the weighted rate of recurrence was 75.0%, 92.5%, and 96.8% at 1, 3 and 5 years, respectively. Among cfDNA-negative patients, the weighted rate of recurrence was 35.7%, 59.7% and 60.7% at 1, 3 and 5 years, respectively. Sensitivity and specificity of cfDNA positivity was 67.8% and 30.0% for recurrence within 1 year, 60.9% and 15.7% for recurrence within 3 years, and 61.5% and 7.6% for recurrence within 5 years, respectively. Conclusions cfDNA-positivity following resection of CRCLM is highly prognostic of recurrence, which may have implications for treatment escalation strategies for this molecularly selected cohort. In contrast, recurrence was common in the cfDNA-negative cohort, cautioning against de-escalation strategies for these patients.