Management of Elevated CA-125
For a patient with elevated CA-125, immediately obtain transvaginal ultrasound with color Doppler as first-line imaging, followed by comprehensive CT imaging of chest/abdomen/pelvis, and measure additional tumor markers (CEA and CA 19-9) to distinguish ovarian from gastrointestinal malignancy. 1, 2
Initial Diagnostic Workup
Imaging Studies
- Transvaginal ultrasound with color or power Doppler is the primary imaging modality to evaluate for ovarian masses, looking specifically for solid components, papillary projections, thick septations, ascites, or complex masses that indicate malignancy 1
- Follow with comprehensive CT scan of chest/abdomen/pelvis, MRI, or PET-CT as clinically indicated 3, 2
- Use the O-RADS US risk stratification system: O-RADS 2 (<1% malignancy risk), O-RADS 3 (1-10%), O-RADS 4 (10-50%), and O-RADS 5 (≥50% risk) 1
Laboratory Evaluation
- Measure CEA and CA 19-9 alongside CA-125 to help distinguish primary ovarian tumors from gastrointestinal metastases 1, 2
- Calculate CA-125/CEA ratio: a ratio >25 favors ovarian origin over gastrointestinal origin 1, 2
- If either CEA or CA 19-9 is elevated, especially with CA-125/CEA ratio <25:1, consider endoscopy to evaluate for gastrointestinal primary 1
Context-Specific Management
For Postmenopausal Women
Immediate referral to a gynecologic oncologist is warranted for postmenopausal women with elevated CA-125, particularly those with nodular or fixed pelvic mass, metastatic disease, ascites, or family history of breast/ovarian cancer 1
For Patients with Known Ovarian Cancer History
Rising CA-125 Without Previous Chemotherapy
- Manage as newly diagnosed disease with appropriate surgical debulking if imaging confirms recurrence 3, 2
- Monitor with pelvic exams every 2-3 cycles, CBC with platelets, chemistry profiles, and CA-125 before each chemotherapy cycle 3
Rising CA-125 After Previous Chemotherapy
- Consider observation until clinical symptoms arise rather than immediate treatment, as treating asymptomatic CA-125 rises may not improve survival and could decrease quality of life 2
- Alternative options include tamoxifen or other hormonal agents, clinical trial enrollment, or observation 2
- Require two elevated CA-125 values at least one week apart to confirm progression 1
- Rising CA-125 typically precedes clinical relapse by 2-6 months 1
Critical Pitfalls and Caveats
CA-125 Limitations
- Only 50% of stage I ovarian cancers produce elevated CA-125, making it a poor screening tool for early disease 1
- CA-125 is elevated in approximately 85% of advanced epithelial ovarian cancers but only 50% of early-stage cases 1, 4
Benign Causes of Elevation
- Do not test CA-125 in patients with ascites of any cause—it is universally elevated and nonspecific 1
- Cirrhosis with ascites universally elevates CA-125 because mesothelial cells under pressure from fluid produce the antigen 1
- Endometriosis, pelvic inflammatory disease, ovarian cysts, and previous radiotherapy can elevate CA-125 1
- Very high levels (>1,000 IU/ml) can occur with benign conditions including uterine myomas and endometriomas 5
Non-Ovarian Malignancies
- Breast cancer and lung cancer are overrepresented among women with elevated CA-125 6
- Colorectal cancer can also elevate CA-125 1
- If ovarian cancer is excluded, investigate for possible breast or lung cancer 6
Progressive Rise in Normal Range
Three progressively rising CA-125 values in the normal range (<35 U/ml) at 1-3 month intervals are associated with high likelihood of tumor recurrence in patients with ovarian cancer history, warranting immediate investigation 7
Follow-Up Protocol
For Confirmed Ovarian Cancer
- Visits every 2-4 months for 2 years, then every 3-6 months for 3 years, then annually after 5 years 2
- CA-125 monitoring at each visit if initially elevated 3, 2
- CBC and chemistry profile as clinically indicated 3, 2