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How reliable are tumour marker tests for ovarian cancer?

Tumour markers are substances found in the blood that are frequently also found in cancer patients. Ovarian cancer tumour markers tests include CA125, CA19.9 and HE4.

person holding a tube of blood

Because CA125 gets produced by cells of the inner lining, conditions such as irritable bowel syndrome, appendicitis, liver or kidney disease, endometriosis or fibroids cause elevated CA125 levels. Sometimes even patients with rheumatoid arthritis have high CA125 levels. Also, there are different sub-types of ovarian cancer with some more likely to report high CA125 than others. The CA125 test has also shown to be more reliable in postmenopausal women. In summary, CA125 is expressed in the majority of patients diagnosed with ovarian cancer but it is not reliable.

CA125 is a tumour marker expressed by the majority of ovarian cancer patients at stages 3 and 4 but up to 50% of patients with stage 1 ovarian cancer don’t have elevated blood concentrations of CA125. CA125 gets produced by the inner lining of the abdomen, chest and the heart. CA stands for cancer antigen. It is an appropriate test for women who have suspected or confirmed ovarian cancer, are investigating a pelvic mass, or are experiencing other ovarian cancer symptoms. CA125 is not recommended as a screening test for women with no symptoms because a normal CA125 test cannot be used to rule out ovarian cancer. High levels of CA125 can also be caused by common conditions such as ovulation or menstruation. 

Other tumour markers for ovarian cancer include CA19.9 which indicates the presence of mucinous subtypes of ovarian tumour, and is also used to indicate the presence of other cancers such as bowel or pancreatic.

HE4 is a protein that is produced by some epithelial ovarian cancer cells. HE4 could complement CA125 and diagnose early-stage ovarian cancers that are negative for CA125. The greatest use of HE4 is to exclude ovarian cancer in elderly and multi-morbid women who we can spare surgical exploration. The HE4 test is rarely elevated in mucinous epithelial ovarian cancers or germ cell tumours, and can also be elevated in non-cancerous diseases. HE4 sometimes is also elevated in patients with endometrial (uterine) cancer.

Overall, tumour marker tests are just one test that may be used to help diagnose ovarian cancer. Transvaginal ultrasound should be used in conjunction with the CA125 test to diagnose ovarian cancer, which can then only be confirmed upon a tissue sample and analysis under a microscope.

During treatment

For ovarian cancer that produces CA125 or other tumour markers these tests may be used to check response to treatment. If CA125 levels are rising during treatment this may indicate that the cancer is not responding to treatment. CA125 levels that decrease may mean the treatment is responding well. However, this is only one method used to check your response to treatment. After treatment is completed CA125 may also be used to monitor for a cancer recurrence.

Overall, all of the above tumour markers can be raised for other reasons that are not related to cancer therefore the test is not completely reliable. These tests alone are not useful as a screening test for ovarian cancer and is only used in people where ovarian cancer is suspected, or during treatment to monitor response. Research continues to search for tumour markers that are more accurate and reliable.

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