Biochemical Tests for Adnexal Mass Evaluation
CA-125 is the primary biochemical test recommended for evaluating adnexal masses, but it should only be used in conjunction with ultrasound findings—never as a standalone diagnostic tool—because it performs worse than ultrasound alone in distinguishing benign from malignant lesions. 1
CA-125 Testing Strategy
When CA-125 Adds Diagnostic Value
CA-125 improves specificity to 100% only when the mass is already suspected to be malignant on ultrasound AND the CA-125 cutoff is raised to 65 U/mL (not the standard 35 U/mL) in the presence of a resistive index <0.5 on Doppler. 1, 2
CA-125 has only 50% sensitivity for stage I ovarian cancer, making it inadequate for early disease detection, but sensitivity increases to 80% for stage II or greater disease. 1
Critical Limitations to Recognize
CA-125 alone performs worse than ultrasound in differentiating benign from malignant masses because it is frequently low in borderline tumors and low-grade malignancies. 1, 2
False-positive CA-125 elevations occur with endometriosis, benign ovarian cysts, pregnancy, pelvic inflammatory disease, pancreatic cancer, and cirrhosis. 1
CA-125 fluctuates widely during early pregnancy and the immediate postpartum period, rendering it clinically useless during these times. 1
Additional Tumor Markers for Specific Scenarios
Epithelial Tumor Differentiation
CA-19-9 and CEA can be ordered when trying to differentiate ovarian primary from gastrointestinal primary neoplasms—a high CA-125/CEA ratio optimizes specificity for ovarian origin. 1
These markers have limited individual specificity but help determine tumor histology preoperatively when used in combination. 1
The Correct Diagnostic Algorithm
Step 1: Ultrasound First, Always
- Perform comprehensive transvaginal ultrasound with color Doppler as the initial and primary diagnostic modality—this achieves >90% sensitivity and provides superior diagnostic accuracy compared to CA-125. 2
Step 2: Risk Stratification Based on Ultrasound Morphology
- Use standardized classification systems (O-RADS, IOTA simple rules) to categorize masses as benign, indeterminate, or suspicious based on imaging features. 2
Step 3: Selective CA-125 Use
Order CA-125 only for masses that appear suspicious or indeterminate on ultrasound—not for clearly benign-appearing masses. 2
In postmenopausal women with suspicious features, CA-125 adds more value than in premenopausal women due to fewer confounding benign conditions. 3
Step 4: Interpretation in Context
When CA-125 is elevated (>65 U/mL) AND ultrasound shows suspicious features with low resistive index (<0.5), refer immediately to gynecologic oncology. 1
When CA-125 is normal but ultrasound shows high-risk features (solid components, papillary projections, ascites, irregular septations), do not be falsely reassured—proceed with gynecologic oncology referral based on imaging alone. 2
Common Pitfalls to Avoid
Never order CA-125 as a screening test in asymptomatic women or as the sole determinant of malignancy risk—this leads to unnecessary surgeries for benign conditions and missed diagnoses of low-grade malignancies. 1, 2
Do not use the standard CA-125 cutoff of 35 U/mL when trying to maximize specificity—the 65 U/mL threshold with Doppler correlation provides 100% specificity. 1
Recognize that CA-125 has higher correlation with clinical course during chemotherapy and predicting recurrence than with initial diagnosis. 1
In women with breast cancer history presenting with adnexal masses, CA-125 levels are significantly higher in metastatic disease to the ovary compared to primary ovarian cancer, but this distinction requires surgical pathology for confirmation. 4