Circulating Tumor DNA in Ovarian Cancer: Emerging Roles in Early Detection, Risk Stratification, and Disease...

Early diagnosis of ovarian cancer remains one of the most important unmet needs in gynecologic oncology because survival is strongly stage-dependent and most patients still present with disseminated disease. Conventional non-invasive tools, particularly CA-125, transvaginal ultrasound, and composite triage algorithms, remain clinically useful but are limited by suboptimal sensitivity for stage I disease and by reduced specificity in premenopausal women and in benign inflammatory or endometriosis-associated conditions. Circulating tumor DNA (ctDNA) has therefore emerged as a candidate biomarker capable of extending liquid biopsy beyond conventional serology. In ovarian cancer, however, ctDNA implementation is constrained by low tumor shedding in early-stage disease, marked biologic heterogeneity across histotypes, clonal hematopoiesis-related background noise, and major pre-analytical and analytical sources of variability. This narrative review, informed by structured searches of PubMed, Scopus, and Web of Science, examines the evolving evidence for ctDNA mutations, methylation-based assays, multi-omic platforms, and machine-learning models across three distinct clinical contexts: population screening, preoperative triage of adnexal masses, and post-treatment assessment of molecular residual disease. We also discuss positive predictive value, false-positive harms, health-economic implications, standardization initiatives, and ongoing prospective studies. Overall, current evidence suggests that the most plausible near-term role for liquid biopsy in ovarian cancer is not as a universal stand-alone screening test, but as an integrated component of risk stratification and disease-monitoring frameworks that combine molecular signals with clinicopathologic and imaging data.