TITLE:
Clinical Utility of Cancer Antigen 125 in the Evaluation of Suspected Ovarian Cancer: Evidence and Diagnostic Pathways
AUTHORS:
Sonali Gupta, Rupali Banzal, Ravindra H. Mahajan, Arul Prakash Pandian James
KEYWORDS:
Ovarian Cancer, CA 125, Transvaginal Ultrasound, Risk of Malignancy Index (RMI), ROMA, ROCA, NICE Guidelines, Biomarker, Artificial Intelligence
JOURNAL NAME:
Open Journal of Obstetrics and Gynecology,
Vol.15 No.11,
November
3,
2025
ABSTRACT: Background: Ovarian cancer remains the most lethal gynaecological malignancy, with survival closely linked to stage at diagnosis. Cancer antigen 125 (CA 125) is a long-established biomarker that, when interpreted within clinical context, aids early identification of women at risk. Objective: This narrative review evaluates the biological basis, diagnostic performance, and contemporary clinical role of CA 125 in the evaluation of suspected ovarian cancer, integrating evidence across primary and secondary care and summarising cost-effectiveness and emerging adjuncts. Methods: A narrative synthesis was conducted using PubMed, Web of Science, and guideline databases to March 2025. Studies describing CA 125 performance, transvaginal ultrasound (TVUS) integration, or validated risk algorithms (RMI, ROMA, ROCA) were prioritised. Evidence from population cohorts, meta-analyses, and national guidance (NICE NG12, CG122, NG241) was reviewed. Results: CA 125 shows pooled sensitivity of ~78% and specificity of ~87% in secondary-care populations with adnexal masses but markedly lower positive predictive value in primary care (≈10% at ≥35 U/mL). Combining CA 125 with TVUS or composite indices such as the Risk of Malignancy Index improves triage accuracy. Population screening using CA 125—alone or with ROCA—does not reduce ovarian-cancer mortality and is not cost-effective. In high-risk women declining or deferring risk-reducing salpingo-oophorectomy, ROCA-based surveillance may be a cost-effective interim option. Emerging markers (HE4) and artificial-intelligence-based ultrasound classifiers enhance discrimination but require prospective validation. Conclusions: CA 125 remains integral to symptom-led diagnostic pathways when combined with structured imaging and risk algorithms. Its limitations—reduced sensitivity in early-stage disease and non-specific elevation in benign states—preclude population screening but support selective use for triage, early referral, and multidisciplinary management.