Laboratory Testing to Rule Out Ovarian Cancer in Postmenopausal Women
For a postmenopausal woman with a suspicious pelvic mass, order CA-125 as the primary tumor marker, and consider additional markers (inhibin, AFP, beta-hCG) only if clinically indicated based on age and imaging characteristics. 1
Primary Laboratory Test
- CA-125 is the only biomarker routinely recommended for evaluating suspected ovarian cancer in postmenopausal women with a pelvic mass 1, 2
- The standard threshold is 30-35 U/mL, which has a specificity of approximately 98.5% for women over age 50 3, 4
- CA-125 has important limitations: it detects only 50% of stage I ovarian cancers, meaning normal levels do not exclude early disease 3, 5
Additional Tumor Markers (Selective Use Only)
The NCCN guidelines specify that additional tumor markers should be measured only if clinically indicated based on specific circumstances 1:
- Inhibin: Consider in postmenopausal women with solid ovarian masses (may suggest granulosa cell tumor)
- AFP (alpha-fetoprotein): Consider primarily in women younger than 35 years with a pelvic mass to assess for germ cell tumors 1
- Beta-hCG: Consider to rule out pregnancy and assess for germ cell tumors in reproductive-age women 1
- CA 19-9 and CEA: Consider for mucinous histology to distinguish primary ovarian cancer from gastrointestinal metastases 6
Important Caveats About CA-125
False-positive elevations occur frequently with benign conditions including 3:
- Endometriosis
- Adenomyosis
- Pelvic inflammatory disease
- Benign ovarian cysts
- Other inflammatory conditions
Progressive elevation over time, even within the normal range, warrants further evaluation as it may indicate malignancy 3
Tests NOT Recommended
- HE4 and ROMA (Risk of Ovarian Malignancy Algorithm): The NCCN panel explicitly does not recommend these biomarkers for determining the status of an undiagnosed pelvic mass, despite FDA approval 1
- OVA-1 multimarker panel: Should not be used as it increases cost without providing clinical benefit and has a positive predictive value of only 2% in average-risk women 4
- Routine screening panels: No laboratory test is recommended for screening asymptomatic postmenopausal women 1, 2
Clinical Context for Laboratory Ordering
Laboratory testing should be integrated with imaging findings 1:
- Order labs after initial pelvic examination and transvaginal ultrasound or CT/MRI
- CA-125 is most useful when imaging shows concerning features (solid components, papillary projections, ascites, bilateral masses)
- For simple cysts without concerning features, CA-125 testing is NOT routinely indicated as it provides limited diagnostic value 3
Common Pitfalls to Avoid
- Do not rely on CA-125 alone to rule out ovarian cancer—it misses 50% of early-stage disease 3
- Do not order comprehensive tumor marker panels routinely—this increases false positives and unnecessary interventions 4
- Do not use laboratory values in isolation—they must be interpreted alongside imaging characteristics, menopausal status, and clinical presentation 1, 2
- Do not delay referral to gynecologic oncology while waiting for tumor marker results if imaging is highly suspicious for malignancy 2, 7