Are CA 125 (Cancer Antigen 125) or CEA (Carcinoembryonic Antigen) elevated in metastatic cervical or uterine cancer?

CA-125 and CEA Elevation in Metastatic Cervical and Uterine Cancer

CA-125 is frequently elevated in metastatic uterine (endometrial) cancer and cervical adenocarcinoma, while CEA shows more limited elevation primarily in cervical adenocarcinoma; neither marker is reliably elevated in cervical squamous cell carcinoma. 1, 2

Cervical Cancer

Adenocarcinoma of the Cervix

CA-125 demonstrates the strongest clinical utility in cervical adenocarcinoma, particularly in advanced and metastatic disease:

• CA-125 is elevated in approximately 60% of patients with cervical adenocarcinoma when considering all stages, with higher rates in advanced disease 2, 3
• In metastatic/recurrent cervical adenocarcinoma, all 15 patients with abdominal recurrence showed CA-125 elevation, making it highly sensitive for detecting metastatic spread 1
• CA-125 levels correlate directly with clinical stage in adenocarcinoma, with higher stages showing greater frequency of elevation 1, 4
• Adenosquamous tumors show even higher rates of CA-125 elevation compared to pure adenocarcinomas, particularly in stages IB and II 1, 4

CEA shows moderate elevation in cervical adenocarcinoma:

• CEA is elevated in 33-48% of cervical adenocarcinoma patients, with levels correlating with clinical stage 2, 3
• CEA elevation is associated with lymph node metastases (P = 0.008), making it a useful marker for metastatic spread 3
• Combined CA-125 and CEA testing increases sensitivity to 70% for detecting cervical adenocarcinoma 2

Squamous Cell Carcinoma of the Cervix

Neither CA-125 nor CEA are reliable markers for cervical squamous cell carcinoma:

• CA-125 is elevated in only 21% of cervical squamous cell carcinoma patients, making it a poor marker for this histology 5, 2
• CEA shows similarly limited utility in squamous cell carcinoma 2
• SCC antigen (not CA-125 or CEA) is the preferred marker for cervical squamous cell carcinoma, elevated in 63% of cases 5

Uterine (Endometrial) Cancer

CA-125 is the primary tumor marker for endometrial cancer, particularly in advanced and metastatic disease:

• More than 50% of patients with advanced-stage or high-grade endometrial cancer have elevated pretreatment CA-125 levels 6
• CA-125 should be considered in select endometrial cancer patients with advanced disease, serous histology, or elevated pretreatment levels 6
• CA-125 accounts for 15% of asymptomatic recurrence detection in endometrial cancer, with sensitivity of 62-74% for detecting recurrence 6

CEA has minimal utility in endometrial cancer and is not routinely measured 7

Clinical Application for Metastatic Disease

Monitoring Strategy

For metastatic cervical adenocarcinoma:

• Measure both CA-125 and CEA at baseline and during follow-up, as combined testing increases detection rates to 70% 2
• Rising CA-125 levels during follow-up coincide with or precede clinical detection of recurrent disease 1
• CA-125 is particularly useful for detecting abdominal/peritoneal metastases 1

For metastatic endometrial cancer:

• CA-125 is the primary marker, especially in serous histology and advanced disease 6
• Serial measurements require two elevated values at least one week apart to confirm progression 6

Important Caveats

Distinguishing primary site in metastatic disease:

• When evaluating suspected ovarian versus gastrointestinal primary, measure CA-125, CEA, and CA 19-9 together 7, 6
• A CA-125/CEA ratio >25:1 favors gynecologic origin over gastrointestinal origin 6
• Endoscopy should be considered if CEA or CA 19-9 is elevated, especially if CA-125/CEA ratio is <25:1 7, 6

False-positive elevations occur with:

• Endometriosis, pelvic inflammatory disease, and benign ovarian cysts 8, 6
• Cirrhosis with ascites (universally elevates CA-125) 6
• Previous radiotherapy 6