Elevated CA-125 in a 57-Year-Old Postmenopausal Woman
For a 57-year-old postmenopausal woman with elevated CA-125, immediate referral to a gynecologic oncologist is warranted, along with transvaginal ultrasound with color Doppler as the first-line imaging study to evaluate for ovarian malignancy. 1, 2
Initial Diagnostic Workup
Imaging Studies
Transvaginal ultrasound with color or power Doppler is the primary imaging modality and should be performed immediately to assess for ovarian masses, with specific attention to morphological features highly suggestive of malignancy including solid components, papillary projections, thick septations, ascites, or complex masses. 3, 2
The American College of Radiology O-RADS US system provides structured risk stratification: O-RADS 2 indicates <1% malignancy risk, O-RADS 3 indicates 1-10% risk, O-RADS 4 indicates 10-50% risk, and O-RADS 5 indicates ≥50% risk. 3
CT scan of abdomen and pelvis should be obtained as the first-line cross-sectional imaging study if ultrasound shows concerning features or is indeterminate. 4
MRI with IV contrast should be considered for further characterization if ultrasound findings are indeterminate or if there is concern about diaphragmatic involvement. 2, 4
Additional Tumor Markers
Measure serum CEA and CA 19-9 in addition to CA-125 to help distinguish primary ovarian tumors from gastrointestinal metastases. 3, 2
Calculate the CA-125/CEA ratio: if the ratio is ≥25, this favors ovarian origin; if ≤25, proceed with colonoscopy/gastroscopy to evaluate for gastrointestinal primary malignancy. 3, 2
Clinical Context and Interpretation
Why This Matters in Postmenopausal Women
Postmenopausal status significantly increases malignancy risk with elevated CA-125 compared to premenopausal women, with higher incidence of both gynecologic and non-gynecologic cancers. 5
The ACOG/SGO criteria specifically recommend referral for postmenopausal women with elevated CA-125, nodular or fixed pelvic mass, metastatic disease or ascites, or family history of breast or ovarian cancer. 1
In postmenopausal women without vaginal bleeding, the upper limit of normal for CA-125 should be 20 U/mL rather than the traditional 35 U/mL cutoff. 6
Sensitivity Limitations
CA-125 is elevated in approximately 85% of advanced epithelial ovarian cancers but only about 50% of early-stage cases, making imaging essential regardless of the CA-125 level. 3, 2
Do not rely on CA-125 alone to make surgical decisions, as it lacks specificity and can be elevated in numerous benign conditions. 3
Common Pitfalls and Benign Causes
Benign Conditions That Elevate CA-125
Endometriosis, pelvic inflammatory disease, ovarian cysts, uterine leiomyomas (especially with coexisting adenomyosis), and cirrhosis with ascites can all elevate CA-125, sometimes to very high levels (>1,000 U/mL). 3, 7, 8
Cirrhosis with ascites universally elevates CA-125 because mesothelial cells under pressure from fluid produce the antigen; do not test CA-125 in patients with ascites of any cause as it is universally elevated and nonspecific. 3
Previous radiotherapy may cause elevated CA-125 levels. 3
Critical Caveat
- Serosal involvement (peritoneal, pleural, or pericardial fluid) requires cautious interpretation as normal epithelia produce CA-125 antigen, leading to false elevations in conditions like tuberculous peritonitis or pancreatic cancer. 9
Referral Criteria
Immediate gynecologic oncology referral is indicated for postmenopausal women meeting ACOG/SGO criteria, which includes any postmenopausal woman with elevated CA-125, particularly when combined with a pelvic mass on examination or imaging. 1, 4
Subspecialty consultation should be strongly considered before proceeding to surgery in postmenopausal patients with CA-125 >65 U/mL and an abdominopelvic mass, as approximately 74% of such cases represent gynecologic cancers at tertiary centers. 5