Background: Loco-regional treatment strategies of colorectal cancer (CRC) metastases
are evolving, but biological markers that can benefit patients and assist physicians
in clinical decisions are lacking. The primary objective of this systematic review
and meta-analysis is to investigate the current knowledge on circulating DNA and its
clinical utility in predicting outcomes in patients undergoing loco-regional treatment
of CRC metastases. Methods: A systematic search of PubMed, Embase, and Cochrane Central
Register of Controlled Trials was conducted on March 22, 2022. We included studies
on patients undergoing loco-regional treatment of CRC metastases reporting the predictive
or prognostic value of circulating DNA in the blood. Hazard ratios (HR) were pooled
in separate random-effects meta-analyses to investigate if pre- or post-ablation measurements
of circulating DNA were associated with survival. The risk of bias was assessed according
to the Quality in Prognosis Studies tool. Results: Twenty-eight studies with 2868
patients were included, of which 16 studies were eligible for meta-analyses. As expected
in this new research field, a majority of included studies (n = 21/28) had a high
risk of bias in at least one domain. Circulating DNA above the cutoff in a plasma
sample taken before loco-regional treatment was associated with a short recurrence-free
survival [pooled HR = 2.8, 95% confidence interval (CI) 1.4-5.7, n = 162] and overall
survival (pooled HR = 4.7, 95% CI 1.1-20.6, n = 105). Circulating DNA above the cutoff
in a plasma sample taken after loco-regional treatment was associated with a short
recurrence-free survival (pooled HR = 4.5, 95% CI 3.4-6.1, n = 569) and overall survival
(pooled HR = 7.5, 95% CI 2.0-27.3, n = 161). There was limited data on the association
between dynamics in circulating DNA and outcome. Conclusions: Measurements of circulating
DNA can be valuable when selecting and monitoring patients undergoing loco-regional
treatment of CRC metastases. Studies designed to investigate the true clinical utility
of circulating DNA in the context of various ablation modalities are warranted. The
review has been registered at PROSPERO (ID: CRD42022320032)
