Prognostic Value of Circulating Tumor DNA for Minimal Residual Disease Detection in Ovarian Cancer: A Systematic Review and Meta-analysis

Epithelial Ovarian Cancer (EOC) is the most lethal gynecological malignancy, with a high rate of recurrence due to minimal residual disease (MRD). Traditional surveillance methods have limited sensitivity for detecting MRD. ctDNA has emerged as a promising biomarker for real-time tumor monitoring and early detection of MRD. We performed a systematic search of Medline, Embase, and CENTRAL through July 2025. Eligible studies included cohort studies involving adults with EOC that reported ctDNA data, collected post-surgery or after adjuvant chemotherapy. Survival outcomes, including progression-free survival (PFS) and overall survival (OS), were extracted and stratified by ctDNA status (detectable vs. undetectable). All statistical analyses were performed at Review Manager version 5.4. This study is prospectively registered in PROSPERO (CRD420251124631). A total of 1,291 records were identified, of which 11 studies met eligibility criteria, encompassing 627 patients with EOC. The pooled analysis showed that ctDNA positivity after surgery was significantly associated with worse PFS (HR 3.83; 95% CI 2.55- 5.77; I 2 = 5% p < 0.01) and OS (HR 2.84; 95% CI 1.22-6.57; I 2 =0; p < 0.01) compared with ctDNA-negative patients. Similarly, post-adjuvant chemotherapy detection of ctDNA yields worse PFS (HR 4.95) and OS (HR 5.95). Our findings suggest that ctDNA is a novel instrument for MRD detection, and its presence serves as a potent prognostic indicator for recurrence and mortality in ovarian cancer. These results support integrating ctDNA into clinical trial designs and highlight its potential for risk-adapted surveillance and treatment strategies • Post-operative ctDNA enables detection of minimal residual disease and is associated with inferior progression-free and overall survival following surgical resection. • The adverse prognostic impact of post-operative ctDNA persists after completion of adjuvant chemotherapy, suggesting ongoing molecular disease despite clinical remission. • These findings support the clinical utility of ctDNA for minimal residual disease detection and warrant confirmation in prospective clinical trials before implementation of ctDNA-guided risk-adapted strategies.