Laboratory Tests for Evaluating Ovarian Symptoms
For patients presenting with ovarian symptoms (bloating, pelvic/abdominal pain, early satiety, urinary urgency/frequency), order CA-125, complete blood count, comprehensive metabolic panel with liver function tests, and consider additional tumor markers (inhibin, AFP, beta-hCG) based on age and clinical presentation. 1, 2
Core Laboratory Panel
Essential Tests for All Patients
- CA-125: The primary tumor marker, elevated in ~85% of advanced ovarian cancer but only ~50% of early-stage disease 2, 3, 4
- Complete blood count (CBC): To assess for anemia and other hematologic abnormalities 1
- Comprehensive metabolic panel with liver function tests: To evaluate overall organ function and detect metastatic disease 1, 2
Age-Specific Tumor Markers
- For women <35 years with pelvic mass: Measure AFP, beta-hCG, and LDH to assess for germ cell tumors 1, 2
- For all reproductive-age women: Consider beta-hCG to rule out pregnancy 1
Histology-Specific Markers
- For suspected mucinous carcinoma: Add CEA and CA 19-9, particularly if CA-125/CEA ratio is ≤25:1, which suggests gastrointestinal origin rather than primary ovarian cancer 2, 3
- For sex cord-stromal tumors: Measure inhibin levels 1
Critical Interpretation Caveats
CA-125 Limitations
CA-125 is not specific to ovarian cancer and can be elevated in numerous benign conditions, including endometriosis, pelvic inflammatory disease, ovarian cysts, cirrhosis with ascites, and other non-gynecologic malignancies (colorectal, breast cancer). 2, 3 This lack of specificity is why CA-125 alone should never drive surgical decisions. 3
False Positives to Avoid
- Cirrhosis with ascites universally elevates CA-125 because mesothelial cells under pressure produce the antigen—do not order CA-125 in patients with known ascites from liver disease 3
- Previous radiotherapy may cause elevated CA-125 levels 3
- Only 50% of stage I ovarian cancers produce elevated CA-125, making it inadequate as a screening tool 3
Algorithmic Approach to Laboratory Workup
Step 1: Initial Symptom Assessment
When patients present with new and frequent symptoms (>12 days/month) including bloating, pelvic/abdominal pain, difficulty eating/early satiety, or urinary urgency/frequency, proceed with laboratory evaluation. 1, 4, 5
Step 2: Risk Stratification
- High-risk patients (family history of breast/ovarian cancer, known BRCA1/2 or Lynch syndrome): Obtain full tumor marker panel immediately 2, 4
- Standard-risk patients: Begin with CA-125, CBC, and metabolic panel 2
Step 3: Age-Based Protocol
- Age <35 years: Add AFP, beta-hCG, LDH, and inhibin to rule out germ cell and sex cord-stromal tumors 1, 2
- Age ≥35 years: Standard panel unless clinical features suggest non-epithelial histology 1
Step 4: Imaging-Guided Refinement
After initial ultrasound or CT findings:
- If mucinous features present on imaging: Add CEA and CA 19-9; consider gastrointestinal evaluation if CEA elevated or CA-125/CEA ratio <25:1 2, 3
- If solid components, papillary projections, thick septations, or ascites: Proceed urgently with comprehensive staging workup 3
Integration with Imaging
Laboratory tests must be interpreted alongside transvaginal ultrasound and/or CT/MRI imaging—never rely on CA-125 alone for diagnosis. 1, 2 The combination of clinical examination, imaging, and tumor markers provides the diagnostic framework, with pathological examination of tissue being definitive. 2
Monitoring Considerations
For established ovarian cancer patients, serial CA-125 measurements require two elevated values at least one week apart to confirm progression, as rising CA-125 typically precedes clinical relapse by 2-6 months. 3
Common Pitfalls
- Ordering CA-125 in isolation: Always combine with imaging and clinical assessment 2, 3
- Missing mucinous carcinoma origin: Failure to order CEA/CA 19-9 can result in misdiagnosis of gastrointestinal metastases as primary ovarian cancer 2, 3
- Inadequate tumor marker panel in young women: Not checking AFP/beta-hCG in women <35 years delays germ cell tumor diagnosis 1, 2
- Interpreting elevated CA-125 in cirrhotic patients: This is universally elevated and nonspecific in ascites from any cause 3