Tumour Markers: What Do CA-125 and Other Tests Mean?

What is a tumour marker?

Tumour markers are substances made in higher-than-normal amounts by some cancer cells, or by the body in response to cancer, and are usually measured in the blood. Most of these substances are also present in small amounts in healthy tissue and can rise in many conditions other than cancer. So a raised marker on its own does not mean cancer, and a normal result does not rule it out.

What are tumour markers used for?

• Helping with diagnosis: when assessing an ovarian mass seen on ultrasound, together with imaging findings and menopausal status, to estimate risk.
• Monitoring response to treatment: in a patient diagnosed with cancer, to see whether a marker that was high before treatment falls with treatment.
• Follow-up for recurrence: a renewed rise during follow-up may indicate the need for further investigation.

Why are they not used to screen healthy women?

In women at average risk without symptoms, screening with CA-125 and ultrasound has been shown not to reduce deaths from ovarian cancer while increasing unnecessary tests and operations. No major medical organisation recommends these tests for routine screening of the general population. Tumour marker panels added to “check-up” packages often lead to unnecessary anxiety and further tests. The situation is different for women with a family history of ovarian, breast or bowel cancer or who carry a gene change such as BRCA; for them, a personalised follow-up plan is set with genetic counselling.

CA-125

CA-125 is the marker most often used in assessing ovarian cancer. Laboratories usually take values below 35 U/mL as normal, although methods and reference ranges can differ between laboratories. CA-125 is not specific to ovarian cancer; it is also produced by the lining of the uterus, the peritoneum and the linings of the lungs and heart.

Benign conditions that can raise CA-125

• Menstruation
• Endometriosis and endometriomas (chocolate cysts)
• Fibroids and adenomyosis
• Pregnancy, especially the first trimester
• Pelvic inflammatory disease and other abdominal inflammation
• Some benign ovarian cysts
• Liver disease (cirrhosis), pancreatitis, heart failure, fluid in the abdomen or around the lungs

These conditions make CA-125 harder to interpret, especially before menopause. After menopause, a raised CA-125 together with a mass needs closer attention. On the other hand, CA-125 can be normal in some early-stage ovarian cancers and in some cancer subtypes.

HE4 and the ROMA index

HE4 (human epididymis protein 4) can rise particularly in epithelial ovarian cancers. It is less affected than CA-125 by benign gynaecological conditions such as endometriosis, but kidney function, smoking and age can change HE4 levels.

ROMA (Risk of Ovarian Malignancy Algorithm) combines CA-125 and HE4 values with the woman's menopausal status in a formula to help estimate the likelihood that a pelvic mass is malignant. The RMI (risk of malignancy index), which combines ultrasound findings, menopausal status and CA-125, is used for a similar purpose. These calculations are not screening tests; they only help with surgical planning and decisions about referral to a gynaecological oncology centre in women who already have a mass.

Other markers

• CA 19-9: mainly used in pancreatic, biliary and stomach cancers. In gynaecology it may rise with mucinous ovarian tumours, dermoid cysts and endometriomas. It also increases in benign conditions such as bile duct obstruction and pancreatitis, and some people do not produce this marker at all for genetic reasons.
• CEA (carcinoembryonic antigen): used to follow digestive cancers, especially colorectal cancer. With an ovarian mass it can help to tell whether the mass may arise from the bowel. It can be mildly raised in smokers and in inflammatory bowel and liver disease.
• AFP (alpha-fetoprotein): rises in some germ cell ovarian tumours seen in young women (especially yolk sac tumour) and in liver cancer. A rise in AFP is normal in pregnancy, where it is measured for a different purpose in screening tests.
• Beta-hCG: the pregnancy hormone; when it is high, pregnancy is considered first. It is used in the diagnosis and follow-up of gestational trophoblastic disease such as molar pregnancy and in some germ cell tumours (choriocarcinoma, dysgerminoma).
• LDH (lactate dehydrogenase): a non-specific enzyme that rises with tissue damage. It can help in following germ cell tumours such as dysgerminoma.
• Inhibin (A and B): a hormone made by the ovary that varies across the menstrual cycle. A rise is meaningful in sex cord-stromal tumours such as granulosa cell tumours, especially after menopause, and it is used to follow these tumours.

The UK National Institute for Health and Care Excellence (NICE) recommends measuring AFP and beta-hCG in addition to CA-125 in women under 40 with suspected ovarian cancer, because germ cell tumours are more common in this age group.

How are results interpreted?

• The whole picture, not a single number: age, menopausal status, the day of the cycle the blood was taken, symptoms, examination and ultrasound findings are considered together.
• Change over time: during follow-up, how the value changes over time matters more than a single measurement. Where possible, the same laboratory should be used for comparable results.
• Repeat testing: in premenopausal women a borderline-high CA-125 can be repeated outside the period.
• Not a diagnosis: cancer is diagnosed not by tumour markers but, when needed, by surgery and tissue examination (pathology).

If a tumour marker result comes back high, the right step is to review it calmly with the doctor who requested it. Comparing the result with reference values on the internet on your own often causes unnecessary anxiety.

Frequently Asked Questions

The information on this website is for general information only and does not replace a medical consultation.

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