Among the most common cancers globally among women, ovarian cancer has the highest mortality rate of gynecologic cancers. A large portion of deaths and poor prognoses can be attributed to late-stage diagnosis and lack of screening; early detection is an imperative part of reducing morbidity and mortality due to ovarian cancer. Serum CA-125 is used as a diagnostic and prognostic tool, though many early-stage cases may not show elevation in this biomarker. Another biomarker that has recently shown promise is circulating tumor DNA (ctDNA), which can be obtained from a blood sample to detect genetic variations. Analysis of ctDNA targets DNA carrying alterations specific to tumors, and previous literature has shown that it is an effective tool for guidance of clinical decisions and is more widely used in other cancers. This study is a systematic review of the available evidence regarding the diagnostic accuracy of ctDNA for detecting ovarian cancer and its relationship with CA-125. A literature searche for this study was performed using PubMed, Web of Science and EBSCO in April of 2024. The primary goal of this review was to establish the diagnostic accuracy of ctDNA in detecting ovarian cancer, as well as to assess sensitivity, specificity, and overall performance. Inclusion criteria for studies were using plasma and/or serum samples for ctDNA analysis, inclusion of a control group in the study design, and study reporting of diagnostic accuracy metrics of sensitivity, specificity, and area under the receiver operating characteristic curve (AUC). Exclusion criteria for studies were those reporting multiple cancer types in aggregate, conference abstracts, animal studies, and case reports. Risk of bias for included studies was assessed using the Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) tool. Final analysis included 19 observational studies, with sample sizes ranging from 17 to 1052. A total of 7 included studies compared the sensitivity and specificity of ctDNA with those of CA-125. Approaches to identifying and assessing ctDNA varied across studies, but many of the studies used PCR-based methods (14 of 19). Many of the studies also examined methylation status, either of specific genes or of multiple gene panels. Differing thresholds of sensitivity and specificity were achieved by different studies assessing different genes, but many studies achieved >80% sensitivity and >70% specificity. The study with the best results achieved 88.8% sensitivity and 100% specificity. Comparisons of ctDNA to CA-125 showed significantly better performance for ctDNA in early-stage disease, particularly with additional marginal improvements in accuracy for ctDNA in other contexts. Assessments of concordance of ctDNA with tumor tissue DNA showed robust concordance. All included studies were found to be at low risk of bias in the domains assessed. These results show that ctDNA has great potential for the detection of ovarian cancer, especially in early stages. As yet, there is no comprehensive panel of genes that should be assessed to detect ovarian cancer, though several genes are known to be highly correlated with it. Future research should focus on improving sensitivity for ctDNA analysis as well as identifying genes most likely to be consistently associated with ovarian cancer that are detectable in ctDNA analysis. (Summarized from Taliento C, Greco P, Bruni G, et al. Circulating tumor DNA in the diagnosis of ovarian cancer: a systematic review. Int J Gynecol Cancer . 2026;36:102686. doi: 10.1016/j.ijgc.2025.102686).
Linda Van Le (Fri,) studied this question.