Cancer antigen 125

What is cancer antigen 125 (CA 125)?

Cancer antigen 125 (CA 125) is a surface antigen on a high molecular weight glycoprotein recognised by a monoclonal antibody (produced using an ovarian cancer cell line). It is most useful as a marker for non-mucinous ovarian epithelial cancer and indeed is present in up to 80% of cases of advanced ovarian cancer - but is often negative earlier in the disease.

Conditions which may cause elevated CA 125¹

Malignant disease

• Ovarian cancer.

• Endometrial cancer.

• Fallopian tube cancer.

• Other intra-abdominal cancers (pancreatic cancer, stomach cancer, colorectal cancer) and metastases from other sites (eg, breast, lung).

Non-malignant conditions

• Benign ovarian tumours (eg, Meigs' syndrome).

• Endometriosis.

• Pelvic inflammatory disease/salpingitis.

• Pregnancy and menstruation. (CA 125 can increase two- to three-fold during menstruation.)

• Leiomyoma, including fibroids.

• Ascites with non-malignant causes - eg, liver disease (cirrhosis).

• Diverticulosis.

• Pleural and pericardial disease.

• Pancreatitis.

• Heart failure² .

Uses of CA 125

Elevated CA 125 is associated with many conditions - listed above. However, currently it is mainly used when ovarian cancer is suspected and for monitoring after treatment.

Investigation of female patients with symptoms suggestive of ovarian cancer³

CA 125 can be used in the assessment of patients presenting with a pelvic mass. It is, however, a nonspecific test, ie raised in other conditions, many of which are benign (see above).

The National Institute for Health and Care Excellence (NICE) recommends sequential testing of serum CA 125 followed by abdominopelvic ultrasonography if the serum CA 125 level is 35 IU/L or more. Women with clinical findings of ascites and a pelvic or abdominal mass should be referred urgently⁴ .

However CA 125 is nonspecific and raised in other conditions, and the level of CA 125 is only increased in 50% of stage 1 cancers⁵ .

There is also no universally agreed scoring system to triage women with suspected benign or malignant adnexal masses detected by ultrasonography at primary care level. Ovarian masses that are multilocular, bilateral, solid, or associated with ascites and metastasis are extremely suspicious and should prompt rapid referral.

Since NICE guidelines were published in 2011 advocating symptom-triggered testing of CA 125 leading to ultrasound scan where raised, studies have shown that cancers are not detected at an earlier stage but that it may increase the chance of complete tumour removal at surgery^{3 6 7} .

See the separate Ovarian Cancer article for more details on symptoms, signs and early detection of this condition.

Monitoring known patients with ovarian cancer for relapse

A number of reviews have failed to identify survival advantage for the process of monitoring CA 125 in asymptomatic women after treatment^{8 9} . It has often traditionally been used to try to pick up relapse early but is currently not recommended⁵ .

Screening for ovarian cancer

The relatively low prevalence of ovarian cancer means that the positive predictive value of CA 125 as a screening test is extremely low. CA 125 is unreliable in differentiating benign from malignant ovarian masses in premenopausal women because of the increased rate of false positives and reduced specificity¹⁰ . This is because an elevated CA 125 level is also found in so many other conditions. When levels are elevated, serial monitoring can be helpful, as rapidly rising levels are more likely to be associated with malignancy than high levels which are static.

Large studies have evaluated CA 125 as a screening tool in combination with ultrasound scanning to detect ovarian cancer early but results so far have failed to demonstrate benefit¹¹ . Therefore, it is not recommended outside research settings⁵ .

However, CA 125 is still being evaluated as a screening tool for patients at high risk of ovarian cancer, in combination with other tests. The UK Familial Ovarian Cancer Screening Study (UKFOCSS) recruited women over a number of years who had strong family histories or mutations in BRCA1 or BRCA2, to be screened with transvaginal ultrasound scan of the ovaries combined with a CA 125 level regularly and continue to follow this up¹² . A second study, the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS) study reports encouraging early results but further follow-up is awaited before conclusions can be reached¹³ .