CA125 Cannot Reliably Detect Endometriosis
CA125 has limited utility as a diagnostic marker for endometriosis, particularly in minimal and mild disease, and should not be used as a screening or diagnostic test in women presenting with suspected endometriosis. The American College of Obstetricians and Gynecologists explicitly states that serum CA125 levels as a diagnostic marker are limited, especially in women with mild or minimal disease 1.
Diagnostic Performance
The diagnostic accuracy of CA125 for endometriosis is poor:
- Sensitivity ranges from only 24-94% with specificity of 83-93%, making it unreliable for detecting disease 2
- Only 27% of minimal endometriosis cases and 68% of mild cases show elevated CA125, compared to 73% of moderate and 100% of severe cases 3
- Using a cutoff of 16 U/ml, CA125 demonstrates 53% sensitivity and 93% specificity—missing nearly half of all cases 3
- A newer second-generation CA125 assay showed no dramatic improvement in detecting endometriosis compared to older assays 4
Clinical Context and Limitations
CA125 elevation is non-specific and occurs in multiple benign conditions:
- Endometriosis, pelvic inflammatory disease, adenomyosis, menstruation, and other benign ovarian cysts all elevate CA125 1, 5
- The American College of Radiology emphasizes that elevated CA125 in a premenopausal patient with clinical features suggesting endometriosis should not raise concern for malignancy 5
- CA125 levels fluctuate with the menstrual cycle in women with advanced endometriosis, rising during the luteal phase and menstruation 6
Limited Clinical Applications
While CA125 cannot diagnose endometriosis, it has narrow utility in specific scenarios:
- For deeply infiltrating endometriosis types II and III, CA125 shows 36% sensitivity and 87% specificity—useful only for the most severe forms that are clinically difficult to detect 6
- In women with advanced endometriosis and initially elevated CA125, the marker may help monitor for recurrence after treatment, with 84% correlation with clinical course 3
- CA125 measurement in ovarian cyst fluid (not serum) can differentiate corpus luteum cysts from endometriotic cysts 6
Critical Pitfall to Avoid
Do not use CA125 to monitor therapy response—ten women with persistent endometriosis confirmed by laparoscopy during danazol treatment had normal CA125 levels (<35 U/ml), demonstrating that normal values do not exclude active disease 7. CA125 is not effective for monitoring therapy 7.
Recommended Diagnostic Approach
Histologic examination via laparoscopy with tissue biopsy remains the gold standard for diagnosing endometriosis 1. The ACOG committee states that only experienced surgeons familiar with the varied appearances of endometriosis should rely on visual inspection alone; otherwise, peritoneal biopsy is required 1.
For women with unexplained pelvic pain, CA125 may be considered as an adjunct to identify deeply infiltrating disease that might otherwise be missed clinically 6, but never as a primary diagnostic tool or to rule out endometriosis.