What Does CA125 Test For?
CA125 is a blood test that measures a high-molecular-weight glycoprotein tumor marker primarily used to monitor ovarian cancer treatment response, detect recurrence, and help differentiate pelvic masses—though it is NOT recommended for screening due to poor sensitivity for early disease and frequent false-positive results from benign conditions. 1, 2
Primary Clinical Applications
Ovarian Cancer Monitoring
- CA125 is most valuable for tracking treatment response and detecting recurrence in patients with known epithelial ovarian cancer, particularly when levels were initially elevated at diagnosis 2, 1
- Approximately 85% of patients with advanced ovarian cancer have elevated CA125, but only 50% of early-stage (Stage I) cases show elevation, severely limiting its utility for early detection 1, 3
- The Gynecologic Cancer InterGroup (GCIG) has established standardized criteria for using CA125 to assess disease response and progression during treatment 2
Diagnostic Limitations
- CA125 should never be used as a standalone screening test for ovarian cancer in average-risk women—the U.S. Preventive Services Task Force explicitly recommends against this (Grade D recommendation) 1
- The positive predictive value for screening is only 2%, meaning 98% of positive screening tests are false positives 4
- Normal CA125 values are typically below 35 U/mL, with specificity of 98.5% for women over age 50, but sensitivity remains poor at approximately 50% for early-stage disease 4, 2
What Conditions Cause CA125 Elevation?
Malignant Conditions
- Epithelial ovarian cancers (especially high-grade serous carcinoma, which accounts for 70% of cases) 3
- Endometrial cancer (where CA125 may serve as a prognostic indicator) 5
- Breast cancer and colorectal cancer can also elevate CA125 3
Benign Gynecologic Conditions
- Endometriosis (can cause significant elevation) 1, 4
- Menstruation (normal endometrium produces CA125) 5, 6
- Pregnancy 5, 7
- Pelvic inflammatory disease 4, 7
- Benign ovarian cysts 1, 7
- Ovarian hyperstimulation syndrome 7
Non-Gynecologic Benign Conditions
- Heart failure (14.7% of patients with elevated CA125 in one study) 8
- Hepatic cirrhosis (11.4% of elevated cases) 8
- Pleural effusion or ascites from any cause 7, 8
- Peritonitis or peritoneal irritation 7, 6
- Chronic lung disease 8
Critical Caveats for Clinical Use
When CA125 Is Helpful
- Serial monitoring during chemotherapy (recommended before each treatment cycle and one month after completion) to assess treatment response 1, 2
- Surveillance after treatment when initially elevated, as rising levels can detect recurrence before clinical symptoms appear 2
- Differentiating tumor origin when combined with other markers: a CA125/CEA ratio >25 favors ovarian over gastrointestinal origin 3
When Additional Testing Is Needed
- For mucinous or endometrioid ovarian tumors, measure CEA and CA19-9 in addition to CA125, as these subtypes may not produce elevated CA125 1, 3
- In young women, always measure alpha-fetoprotein and beta-HCG to exclude germ cell tumors 1
- Progressive elevation of CA125 over time, even within the normal range, warrants further imaging evaluation (CT, MRI, or PET-CT) 4, 2
Common Pitfalls to Avoid
- Do not rely on CA125 alone to rule out ovarian cancer—normal levels do not exclude malignancy, particularly in early-stage or borderline tumors 4
- Markedly elevated CA125 (even >1000-5000 U/mL) can occur with benign conditions like heart failure or cirrhosis, so elevation alone cannot diagnose malignancy 7, 8
- Ultrasound-based models (IOTA Simple Rules, ADNEX model) are superior to CA125 alone for distinguishing benign from malignant ovarian masses 3
Biological Origin
CA125 is an antigenic determinant on a glycoprotein expressed by derivatives of embryonic coelomic epithelium, including Müllerian epithelia (fallopian tubes, endometrium, endocervix), peritoneum, pleura, and pericardium 5, 6. This explains why peritoneal irritation from any cause—including surgery, infection, or fluid accumulation—can elevate serum levels 6, 8.