Indications for CA-125 Testing
CA-125 should be ordered primarily for monitoring treatment response and detecting recurrence in patients with known epithelial ovarian cancer, particularly non-mucinous subtypes, and may be used as an adjunct diagnostic tool in postmenopausal women with pelvic masses suspicious for ovarian malignancy. 1, 2
Primary Clinical Indications
Ovarian Cancer Monitoring and Surveillance
- CA-125 is most valuable for monitoring disease response to treatment and detecting recurrence in patients with established epithelial ovarian cancer, where it is elevated in approximately 85% of advanced disease cases 1, 3, 2
- Measurement should occur at each follow-up visit: every 3 months for 2 years, every 4 months during year 3, and every 6 months during years 4-5 3
- The marker demonstrates 62-74% sensitivity for detecting ovarian cancer recurrence, making it more reliable than physical examination alone (15-78% sensitivity) 4
Diagnostic Adjunct for Pelvic Masses
- CA-125 aids diagnosis when interpreted alongside imaging and clinical findings in postmenopausal women with suspicious adnexal masses 1
- It is elevated in only 50% of early-stage ovarian cancers, limiting its utility for early detection 1, 3
- High-grade serous carcinoma shows the highest CA-125 elevation rates (89% positivity), while mucinous cystadenocarcinoma demonstrates markedly low positivity (only 16%) 1, 5
Selective Use in Endometrial Cancer
- CA-125 should NOT be used routinely in endometrial cancer surveillance 4
- Consider CA-125 only in select endometrial cancer patients with advanced disease, serous histology, or elevated pretreatment levels, where it accounts for 15% of asymptomatic recurrence detection 4
- More than half of patients with advanced-stage or high-grade endometrial cancer have elevated pretreatment CA-125 levels 4
Differential Diagnosis Considerations
Distinguishing Primary Ovarian from Gastrointestinal Malignancy
- Measure CEA and CA 19-9 in addition to CA-125 when evaluating mucinous ovarian tumors or suspected gastrointestinal metastases 1, 3, 2
- A CA-125/CEA ratio >25 favors ovarian origin over gastrointestinal origin 1, 3
- Consider endoscopy if CEA or CA 19-9 is elevated, especially when CA-125/CEA ratio is <25:1 1
Non-Ovarian Malignancies
- Colorectal cancer and breast cancer can produce elevated CA-125 levels 1
- Cervical cancer patients may show elevated levels (mean 226 U/ml), though significantly lower than ovarian cancer (mean 1160 U/ml) 5
Important Limitations and Pitfalls
Benign Conditions Causing False Positives
- Endometriosis, pelvic inflammatory disease, ovarian cysts, cirrhosis, pregnancy, and menstruation can all elevate CA-125 1, 6
- Previous radiotherapy may cause elevated levels 4
- These benign conditions typically show lower elevations than malignancy, but overlap exists 6, 5
Screening Is Not Recommended
- CA-125 is not valid as a screening test for ovarian cancer in asymptomatic women due to insufficient sensitivity (21-33% detection rate) and specificity (75-98% true negative rate depending on cutoff) 7
- Ultrasound-based models (IOTA Simple Rules or IOTA ADNEX) are superior to CA-125 alone for distinguishing benign from malignant ovarian tumors 1
Histology-Specific Performance
- CA-125 performs poorly in mucinous ovarian carcinomas (16% positivity) compared to serous types (89% positivity) 5
- No positive correlation exists between CA-125 levels and FIGO clinical stage 5
Practical Application Algorithm
For suspected ovarian malignancy:
- Order CA-125 alongside comprehensive imaging (CT abdomen/pelvis as first-line) 3
- Add CEA and CA 19-9 if mucinous histology suspected or gastrointestinal primary needs exclusion 1, 3
- Calculate CA-125/CEA ratio to guide differential diagnosis 1
For established ovarian cancer:
- Obtain baseline CA-125 before treatment 3
- Monitor serially during chemotherapy to assess treatment response 5, 8
- Continue surveillance measurements at scheduled intervals for 5 years 3
For endometrial cancer: