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Evaluating the utility of circulating cell-free DNA in the context of endometrial cancer: a systematic scoping review
Journal article   Open access   Peer reviewed

Evaluating the utility of circulating cell-free DNA in the context of endometrial cancer: a systematic scoping review

Eliza Macdonald, Grace Laura Rose, David Simar, Alexandra Leigh McCarthy, Caroline Ford, Kristina Warton, Sandra C Hayes and Briana Kristine Clifford
International Journal of Gynecological Cancer, Vol.36(8), pp.1-9
2026
DOI: https://doi.org/10.1016/j.ijgc.2026.104767
PMID: 42330750
Appears in  Cancer Research Cluster Research Collection
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Published Version Open Access CC BY V4.0

Abstract

Biomarker Cell-Free DNA Circulating Tumor DNA Endometrial Cancer Liquid Biopsy Uterine Cancer
Objective Elevated concentrations of circulating cell-free DNA and circulating tumor DNA (ctDNA) are often detectable in biofluid from individuals with cancer. Investigating cfDNA and ctDNA across the endometrial cancer continuum provides insight into diagnostic and prognostic potential. This systematic scoping review provides an overview of studies evaluating the utility of cell-free DNA ± circulating tumor DNA in endometrial cancer. Methods Databases and clinical trials registries (Embase, PubMed, CINAHL, Scopus, Open Science Framework, ClinicalTrials.gov) were searched using terms related to “Endometrial cancer”, “Cell-free DNA”, and “Circulating tumour DNA”. Primary articles and pre-registered protocols of observational or interventional studies reporting cell-free DNA ±ctDNA measurement using biofluid from individuals with endometrial cancer of any stage, grade, or sub-type, at any time point were included. Results Ninety-three records were identified. Studies evaluated cell-free DNA ± circulating tumor DNA in endometrial cancer for 1) diagnosis; 2) monitoring disease status; 3) molecular profiling; 4) determining prognostic risk. Cell-free DNA ± circulating tumor DNA was primarily isolated from blood and analyzed using PCR-based assays or Next Generation Sequencing. Circulating tumor DNA showed promising diagnostic performance with greater potential in endometrial cancer prognosis, profiling, and monitoring, compared to cell-free DNA. Study design, sample characteristics, and data collection, analysis, and reporting were heterogeneous, limiting the strength of evidence for any given relationship. Conclusions Cell-free DNA ± circulating tumor DNA has promising potential as a clinically valuable marker in endometrial cancer diagnosis, tumor profiling, treatment, and surveillance. However, evidence supporting the clinical use of any given cell-free DNA ± circulating tumor DNA parameter in this cohort is immature and limited by the lack of standardized methods and reporting. Addressing study design limitations, standardizing analysis methods and outcome reporting, and improving understanding of cell-free DNA physiology represent opportunities to advance this field of clinical research.

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