Is CA (Cancer Antigen) 125 the only tumor marker used in the evaluation of a postmenopausal woman with an adnexal mass?

CA-125 is NOT the Only Tumor Marker for Postmenopausal Women with Adnexal Masses

While CA-125 is the primary tumor marker recommended for evaluating postmenopausal women with adnexal masses, additional markers should be measured selectively based on clinical context, imaging characteristics, and CA-125 results. 1, 2

Primary Tumor Marker: CA-125

• CA-125 should be measured before surgery in all postmenopausal women with suspected ovarian cancer, with a specificity of 98.5% when using the standard threshold of 35 U/mL 1, 2
• CA-125 is elevated in approximately 80-90% of serous carcinomas (the most common epithelial ovarian cancer type), but only detects 50% of stage I ovarian cancers 1, 2
• The combination of CA-125 with transvaginal ultrasound provides better diagnostic accuracy than either test alone 2

Additional Tumor Markers: When and Why

CA 19-9

• Should be measured when CA-125 is normal or minimally elevated, particularly if imaging suggests clear cell, mucinous, or endometrioid tumors 2
• CA 19-9 can be elevated in epithelial ovarian neoplasms and helps optimize specificity when combined with CA-125 1

Age-Specific Considerations

• In women younger than 35 years with a pelvic mass, alpha-fetoprotein (AFP) and beta-hCG should be measured to assess for germ cell tumors 3, 2
• While the question specifies postmenopausal women, if the patient is perimenopausal or younger postmenopausal, these markers remain relevant 1

CEA (Carcinoembryonic Antigen)

• A high CA-125/CEA ratio optimizes specificity for distinguishing ovarian primary tumors from gastrointestinal primary neoplasms 1
• CEA can be elevated with epithelial ovarian neoplasms but has limited specificity individually 1

Critical Limitations and Pitfalls

CA-125 Alone is Insufficient

• CA-125 performed worse than ultrasound alone in distinguishing benign from malignant lesions and only improved specificity for lesions already suspected to be malignant on imaging 1, 2
• CA-125 lacks sensitivity for early-stage disease, missing approximately 50% of stage I cancers 1, 2
• False-positive elevations occur with endometriosis, adenomyosis, pelvic inflammatory disease, benign cysts, cirrhosis, and following radiotherapy 4

When CA-125 Provides False Reassurance

• A normal CA-125 level may provide false reassurance in a postmenopausal woman with an intermediate- or high-risk ovarian lesion on imaging 4
• Borderline and low-grade malignant tumors may have normal CA-125 levels 1

Clinical Integration Algorithm

1. Always measure CA-125 first in postmenopausal women with adnexal masses 1, 2

2. Interpret CA-125 in conjunction with transvaginal ultrasound findings (morphology, color Doppler, solid components, papillary projections, ascites) 1, 2

3. Add CA 19-9 if:

   • CA-125 is normal or minimally elevated AND
   • Imaging suggests mucinous, clear cell, or endometrioid histology 2

4. Consider CEA if:

   • There is concern for distinguishing ovarian from gastrointestinal primary tumor 1

5. If mass remains indeterminate after ultrasound and tumor markers:

   • MRI with IV contrast is the next best step (NOT CT) 1, 3

Tests NOT Recommended

• The NCCN panel explicitly does not recommend HE4 and ROMA for determining the status of an undiagnosed pelvic mass, despite FDA approval, due to increased cost without significant benefit and concerns about false-positive results 1, 3
• The OVA1 test is not recommended as it increases cost without providing much benefit and raises concerns about false-positive results 1

Referral Criteria for Postmenopausal Women

Refer to a gynecologic oncologist if ANY of the following are present: 1

• Elevated CA-125
• Nodular or fixed pelvic mass
• Metastatic disease or ascites
• Family history of breast or ovarian cancer