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

Ludovica Pepe1,2, Valeria Zuccalà1, Walter Giuseppe Giordano2

  • 1Anatomic Pathology Unit, Department of Human Pathology in Adult and Developmental Age "Gaetano Barresi", University of Messina, 98125 Messina, Italy.

Cancers
|May 4, 2026
PubMed
Summary

Early diagnosis of ovarian cancer is crucial. Liquid biopsy using circulating tumor DNA (ctDNA) shows promise but requires integration with other data for effective risk stratification and disease monitoring.

Keywords:
CA-125adnexal massescirculating tumor DNActDNA methylationearly detectionliquid biopsymolecular residual diseasemulti-omic biomarkersovarian cancer

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Area of Science:

  • Gynecologic Oncology
  • Molecular Diagnostics
  • Biomarker Discovery

Background:

  • Early ovarian cancer diagnosis is critical due to stage-dependent survival rates, with most patients presenting with advanced disease.
  • Current non-invasive tools like CA-125 and ultrasound have limitations in sensitivity and specificity, especially for early-stage disease and in premenopausal women.
  • Circulating tumor DNA (ctDNA) offers potential for liquid biopsy in ovarian cancer, overcoming limitations of conventional serology.

Purpose of the Study:

  • To review the evolving evidence for ctDNA-based biomarkers in ovarian cancer.
  • To examine ctDNA applications in population screening, preoperative triage, and molecular residual disease assessment.
  • To discuss challenges and future directions for liquid biopsy implementation in ovarian cancer management.

Main Methods:

  • A narrative review based on structured literature searches of PubMed, Scopus, and Web of Science.
  • Examination of evidence for ctDNA mutations, methylation assays, multi-omic platforms, and machine learning models.
  • Discussion of clinical contexts including screening, triage, and post-treatment monitoring.

Main Results:

  • ctDNA implementation in ovarian cancer faces challenges including low shedding in early stages, biologic heterogeneity, and technical variability.
  • Evidence for ctDNA mutations, methylation assays, multi-omic platforms, and machine learning models is evolving across different clinical scenarios.
  • Positive predictive value, false-positive harms, and health-economic implications are key considerations.

Conclusions:

  • Liquid biopsy is unlikely to serve as a universal stand-alone screening test for ovarian cancer in the near term.
  • The most plausible near-term role for liquid biopsy is as part of integrated frameworks combining molecular data with clinicopathologic and imaging information.
  • Further standardization and prospective studies are needed to optimize the use of liquid biopsy in ovarian cancer risk stratification and disease monitoring.