CA-125 is Not the Best Blood Test for Detecting Ovarian Cancer
CA-125 alone is not the best blood test for detecting ovarian cancer due to its limited sensitivity and specificity, especially in early-stage disease where only about 50% of cases produce enough CA-125 to cause a positive test. 1
Limitations of CA-125 as a Standalone Test
Limited sensitivity in early disease: CA-125 has approximately 50% sensitivity in stage I ovarian cancer cases, though it improves to 80-85% sensitivity in stage II or greater disease 2
Poor specificity: CA-125 levels can be elevated in numerous non-cancerous conditions, including:
- Benign gynecologic conditions: endometriosis, adenomyosis, pelvic inflammatory disease, menstruation, uterine fibroids, and benign ovarian cysts 2
- Non-gynecologic conditions: peritonitis, cirrhosis, pancreatic cancer, and conditions causing pleural effusion or ascites 2
- Other cancers: breast, lung, colon, and pancreatic cancer 2
Population limitations: CA-125 has higher specificity in postmenopausal women compared to premenopausal women 2
Better Approaches Than CA-125 Alone
Multimodal Screening Approaches
CA-125 + Transvaginal Ultrasound (TVU): The UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS) assessed a multimodal screening strategy that included annual CA-125 screening using a risk of ovarian cancer algorithm (ROCA) with TVU as a second-line test. This approach was more effective at detecting early-stage ovarian cancer than either modality alone 1
Combined biomarkers: The combination of CA-125 and Human Epididymis Protein 4 (HE4) has proven highly efficient with an area under the curve (AUC) of up to 0.96, making it currently the most efficient biological diagnostic tool for ovarian cancer 3
Algorithmic Approaches
Risk of Ovarian Cancer Algorithm (ROCA): This algorithm uses age and longitudinal changes in CA-125 levels over time rather than single measurements, which may be more effective than a single CA-125 measurement 1
ROMA (Risk of Ovarian Malignancy Algorithm): Combines HE4 and CA-125 measurements, though its specificity (84%) is lower than HE4 alone (94%) 3
Current Recommendations
No professional organization recommends CA-125 alone for screening average-risk women for ovarian cancer 1
The American College of Obstetricians and Gynecologists (ACOG) and the Society of Gynecologic Oncology (SGO) recommend referral to a gynecologic oncologist for any elevation of CA-125, particularly levels greater than 200 units/mL 2
Pattern of CA-125 elevation (progressive increases over time) is more concerning for malignancy than a single elevated value 2
Pitfalls and Caveats
Using CA-125 alone for screening can lead to unnecessary interventions, surgeries, and psychological harm due to false positives 4
CA-125 results must be interpreted in the context of the patient's complete clinical picture, including menopausal status and presence of other conditions that could elevate the marker 2
The high performance of CA-125 reported in some studies may be due to recruitment bias, restriction to postmenopausal women, and inclusion of only primary invasive epithelial ovarian cancer cases 5
In conclusion, while CA-125 remains widely used in ovarian cancer evaluation, it is most valuable when combined with other biomarkers (particularly HE4) and imaging modalities (transvaginal ultrasound) rather than as a standalone test for detecting ovarian cancer.