Circulating tumor DNA in the diagnosis of ovarian cancer: a systematic review

Ovarian cancer remains a leading cause of gynecologic cancer mortality worldwide, largely due to late-stage diagnosis and limited early detection tools. Circulating tumor DNA (ctDNA) has emerged as a promising non-invasive biomarker with the potential to improve diagnostic accuracy through detection of tumor-specific genetic and epigenetic alterations.

This systematic review aimed to evaluate the diagnostic accuracy of ctDNA in detecting ovarian cancer compared to healthy controls or benign conditions. A comprehensive literature search was conducted across PubMed, Web of Science, and EBSCO databases through April 2024, including studies that assessed sensitivity, specificity of ctDNA assays in plasma or serum samples. Risk of bias was assessed using the Quality Assessment of Diagnostic Accuracy Studies-2 tool. PROSPERO registration number: CRD42024590089.

Nineteen studies met inclusion criteria, employing a variety of molecular techniques including polymerase chain reaction-based methylation assays (73.7%) and sequencing methods (whole genome sequencing/next-generation sequencing) (21%), targeting single genes or multi-gene panels. Diagnostic accuracy of ctDNA varied, with sensitivity (40.6%-94.7%) and specificity (56%-100%) ranging broadly, but often outperforming CA125, particularly in early-stage. Concordance between ctDNA and tumor tissue ranged from moderate (r = 0.428) to strong (r = 0.771).

Although heterogeneity across studies precluded meta-analysis, narrative synthesis suggests that ctDNA may offer an improved early detection capability over CA125, through methylation and copy number variation analyses. Further controlled prospective studies are needed to validate the clinical utility of ctDNA as a complementary tool in ovarian cancer detection.