Raised CA-125: What are the Causes?

CA-125 is a protein found mostly in certain types of cancer cells. CA stands for cancer antigen and CA-125 is known as a tumour-marker especially for ovarian cancer.

CA-125 is traditionally done to measure the success of ovarian cancer treatment or when a pelvic mass is found. It is not suggested to be used as a screening test for ovarian cancer because it is not accurate with high probability of false positive and false negative results. CA-125 can be high in certain cancers other than ovarian cancer, and in other non-cancerous condition as well.

     Female reproductive organs

Here is a list of conditions which can cause a raised CA-125:

Cancer

• Ovary
• Uterus/endometrium
• Fallopian tube
• Breast
• Pancreas
• Liver
• Lungs
• Bowel
• Bladder
• Cancer with peritoneum involvement

Non-cancer (gynecological)

• Benign ovarian cyst
• Endometriosis
• Fibroid
• Pelvic inflammatory disease
• Pregnancy (first trimester)
• Menstruation

Non-cancer (non-gynecological)

• Pancreatitis
• Liver cirrhosis/failure
• Renal failure
• Nephrotic syndrome

The normal value of CA-125 is <35 u/ml. If you have a level higher than 35, then you should have an ultrasound scan to check your ovaries and uterus. Your doctor will take relevant history from you and examine you thoroughly. If nothing can be found, usually you are only required to repeat the test at an interval and follow up with the doctor.

If a pelvic/ovarian mass is found, depends on its characteristic, a surgery may be required to confirm whether it is cancerous or not. Sometimes it can just be a benign (non-cancerous) ovarian tumour or endometriod cyst.

However, not everyone with confirmed ovarian cancer will have an abnormal CA-125 results. Only about 50% of stage I ovarian cancer patients have raised CA-125. For stage II, III, IV ovarian cancer patients, 80% will have raised CA-125 while for the rest of 20% of these patients, their CA-125 level remain normal.

A study done in 1999 by IJ Jacobs screen about 10,000 post-menopausal women over 45 years old using the CA-125 test alone. Results of this study showed a false positive rate of about 80%. (only 20% of these women with abnormal CA-125 had ovarian cancer)

Another study screened 11,000 post-menopausal women over 45 years old with CA-125. As a result, 468 of them were found to have raised CA-125 and ultrasound scan were done. Of these 468 women, 29 underwent surgical procedure and noted:

• 6 had ovarian cancer (1.3% - 6 out of 468)
• 2 had adenocarcinoma of unknown origin
• 14 had benign tumour
• 4 had fibroids
• 3 had no abnormality

We can see that the false positive rate of CA-125 test varies from different studies, but we know that the chance of ovarian cancer with a raised CA-125 is not very high. However, this should not be the reason for us to ignore the positive result. To improve the accuracy of the test, a serial CA-125 tests should be done to see the trend, and ultrasound scan should be performed.