What is CA (Cancer Antigen) 125 used for and how is it correlated with other diagnostic tests?

CA-125: Clinical Uses and Diagnostic Correlation

CA-125 is a tumor marker primarily used for monitoring treatment response and detecting recurrence in epithelial ovarian cancer, NOT for screening, and should be correlated with imaging studies (CT, MRI, or PET-CT) to validate clinical significance. 1

Primary Clinical Uses

Monitoring Established Ovarian Cancer

• CA-125 is most valuable for tracking disease response to chemotherapy and detecting recurrence in patients with proven epithelial ovarian cancer, particularly when levels were initially elevated at diagnosis 1, 2
• The NCCN recommends measuring CA-125 at every follow-up visit (every 2-4 months for 2 years, then every 3-6 months for 3 years, then annually) if the marker was initially elevated 3
• Serial CA-125 monitoring can detect recurrent disease 2-6 months before clinical symptoms appear, though early treatment based solely on rising CA-125 does not improve survival or quality of life 3

Differential Diagnosis of Pelvic Masses

• CA-125 helps differentiate benign from malignant pelvic masses when combined with imaging, with normal values typically below 35 U/mL and specificity of 98.5% in women over 50 years 1
• The marker has approximately 80% sensitivity for stage II or greater ovarian cancer but only 50% sensitivity for stage I disease, making it inadequate as a standalone screening tool 1, 2

Critical Limitations

Poor Screening Performance

• CA-125 should NOT be used for ovarian cancer screening in asymptomatic women due to high false-positive rates and lack of mortality benefit 1, 4
• The positive predictive value is only about 2% in average-risk women, meaning 98% of positive tests are false positives 5

Benign Conditions Causing Elevation

• Common false-positive causes include endometriosis, pelvic inflammatory disease, benign ovarian cysts, menstruation, pregnancy, peritonitis, pleural effusion, ascites, and cirrhosis 1, 6, 4
• Cirrhosis with ascites universally elevates CA-125 because mesothelial cells under pressure produce the antigen 6, 7
• Elevations up to 1000-5000 U/mL can occur in benign conditions, limiting diagnostic specificity 4

Correlation with Other Tests for Validation

Imaging Studies (Essential Correlation)

• When CA-125 is elevated or rising, imaging with chest/abdominal/pelvic CT, MRI, or PET-CT is indicated to evaluate for actual disease presence 3, 1
• Transvaginal ultrasound with color or power Doppler is the primary imaging modality for evaluating pelvic masses, looking for solid components, papillary projections, thick septations, or ascites 6
• MRI with IV contrast is superior to CT for characterizing indeterminate adnexal masses 5

Additional Tumor Markers

• Measuring CEA and CA 19-9 alongside CA-125 helps distinguish primary ovarian tumors from gastrointestinal metastases 6, 2
• A CA-125/CEA ratio >25 favors ovarian origin over gastrointestinal origin 6
• CA 19-9 offers high sensitivity for mucinous ovarian tumors, which often fail to express CA-125 (only 16% positivity in mucinous cystadenocarcinoma) 2, 8

Clinical Assessment

• Physical examination including pelvic exam should accompany CA-125 monitoring at each visit 3
• Complete blood count and chemistry profile should be obtained as clinically indicated 3

Histologic Specificity

• CA-125 shows highest sensitivity (89%) for serous cystadenocarcinoma but markedly low sensitivity (16%) for mucinous cystadenocarcinoma 8
• High-grade serous carcinoma accounts for 70% of epithelial ovarian cancers, making CA-125 useful in the majority of cases 6

Other Malignancies with CA-125 Elevation

• Non-gynecologic cancers that can elevate CA-125 include colorectal cancer, breast cancer, and pancreatic cancer 6, 7
• CA-125 is also useful in select endometrial cancer patients with advanced disease, serous histology, or elevated pretreatment levels 6

Key Clinical Pitfalls

• Never use CA-125 alone to make surgical decisions—always correlate with imaging and clinical findings 6
• Avoid testing CA-125 in patients with ascites of any cause, as it is universally elevated and nonspecific 6
• Progressive elevation of CA-125 over time, even within normal range, may indicate malignancy and warrants further evaluation 1, 5
• The Society of Gynecologic Oncology recommends discussing the pros and cons of CA-125 monitoring with patients, as treating recurrences early based solely on elevated CA-125 does not improve survival 3