CA 125: a Predictor in Ovarian Carcinoma, Endometrial Cancer and other Carcinomas
Jian Q. Wang, M.D.*

CA 125, a high molecular weight (>200 kD) glycoprotein, is expressed on the surface of coelomic epithelium and recognized by the murine monoclonal antibody OC125.1 The second generation CA 125 II assay which uses two monoclonal antibodies, OC125 and M11, correlates well with CA 125 but does not demonstrate interference with human antimouse antibodies (HAMA).2

CA125 measurement is used clinically for prognosis, early diagnosis of recurrence and follow-up in patients with carcinomas. Measuring the serum level of CA-125 antigen is a less expensive method to detect recurrent cancers than radioimmunoscintigraphy.33 Combined with CEA, CA19-9, and breast cancer antigen 225 (BCA225), CA125 can be used for the differential diagnosis of a metastatic adenocarcinoma.32

Serum CA 125 concentration is >35 U/mL in about 80% of women with carcinoma of the ovary,3-5 26% of women with benign ovarian tumors3,5,6 and 66% of patients with non-neoplastic conditions including the first trimester of pregnancy, menstruation, endometriosis, adenomyosis, uterine fibroids, acute salpingitis, hepatic diseases (e.g., cirrhosis) and inflammation of the peritoneum, pericardium and pleura. Only 3% and 0.8% of normal healthy control women have a serum CA 125 concentration over 35 and 65 U/mL, respectively.7-10 Pelvic-peritoneal tuberculosis is associated with elevated serum CA 125.3 In patients with carcinoma that has disseminated beyond the ovary (FIGO stages II, III and IV), 90% have serum concentrations >35 U/mL; however, only 50% of cancer patients whose disease is confined to the ovary (stage I) are positive.1

Combined serum CA 125 (>30 U/mL) and pelvic examination as a screening test for ovarian cancer has a specificity of 99.6% and a positive predictive value of 6-25%.7,8 Transvaginal ultrasound (TVUS) has superior sensitivity and specificity to CA 125 alone, and should be done before interpretation of a CA 125.11-13 Serial determinations of CA 125 with investigation of patients with persistently elevated values increases the positive predictive value in ovarian cancer screening.7 However, low prevalence of the disease in patients without a family history of ovarian cancer results in only one case discovered for every 30 false-positives using ultrasound and CA 125.14-18

The higher the CA 125, the more likely an elevated CA 125 is due to gynecologic cancer. In women with a pelvic mass, a serum CA 125 concentration >35 U/mL, 65 U/mL and 95 U/mL can distinguish malignancy from benign disease with 82%, 93% and 96% accuracy, respectively. When less care is taken in patient selection, the predictive values are much lower.5,6,19,20 In patients with a CA 125 >65 U/mL, gynecologic, non-gynecologic cancers and non-gynecologic conditions constitute 74%, 10% and 13% of diagnosis, respectively. In patients with a CA 125 >1000 U/mL, these same conditions are responsible for 89%, 7% and 3% of diagnosis, respectively.21 Endometriosis and metastatic breast carcinoma are the most common benign and nongynecologic conditions that cause an elevated CA 125. The absence of a pelvic mass makes malignant disease very unlikely.

There may be some utility in pre-screening women with a family history of ovarian cancer with CA 125 prior to referral for ultrasound. Using a cut-off of 20 U/mL as the criterion for ultrasound referral would decrease costs because only 25% would be referred. However, 29% of the true-positive cases detected by a strategy in which all patients are initially screened by ultrasound would be missed by CA 125 pre-screening22,23

CA 125 is useful as a prognostic marker and confirms the clinical impression of the patient. Patients with CA 125 concentrations >450 U/mL have a very poor median survival of 7 months; whereas, patients with a CA 125 concentration <55 U/mL have a better median survival of 23 months.24 Post-operative serum CA 125 predicts 2-year overall survival (>35 U/mL 87%; > 65 U/mL 30%).25 The rate and magnitude of decrease in the CA 125 after the first course of chemotherapy is predictive of prognosis. Patients with a >50% decrease in the CA 125 concentration have a 2-year survival of 45% compared to 22% in patients with a decrease in CA 125 that is <50%.26 An increase to more than 60 U/mL after the first coarse of chemotherapy accurately predicts tumor relapse.1

The most important use of CA 125 is in the assessment of patients for recurrent disease post-oophorectomy. Residual disease is detected in 95% of patients with serum CA 125 concentrations >35 U/mL who are monitored for recurrent ovarian carcinoma. However, a negative result does not exclude the presence of the disease; half of the patients with such negative results have microscopic residual carcinoma. Post surgical monitoring of patients for recurrent ovarian carcinoma is best achieved by combining second-look operations and CA 125 monitoring. 28-29 If the cut-off is lowered to 16 U/mL, 57% of patients considered to be in remission using a cut-off of 35 U/mL are now considered to have recurrent disease.30

CA125 elevation in post-treatment patients of endometrial cancer is also a predictor of recurrence and poor prognosis. Among 23 patients, seven of the 12 (58%) with post-treatment elevation of CA125 developed tumor recurrence. But none of the 11patients (0%) without post-treatment elevation of CA125 developed a recurrence.31
See Also:
Algorithm 5: Ovarian Cancer Monitoring

Relevant Tests Offered by GBMC
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