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.

PSA: Is it a good prostate cancer marker?

Prostate specific antigen (PSA) is a protein produced by cells in the prostate glands. Thus only male has PSA. PSA has been widely used as a screening tool for prostate cancer.

   Location of prostate gland

It is still controversial whether PSA is suitable to be used to screen for prostate cancer. Studies have shown that while most prostate cancer sufferers have raised PSA level, this test is somehow not specific. This means that the false positive rate is quite high. Even though one has high level of PSA, he may not have prostate cancer.

There are a few recognized causes for raised PSA, all of them are associated with irritation of the prostate:

1. Benign Prostatic Hyperplasia – enlarged prostate due to aging
2. Prostatitis – inflammation of prostate (can be infection or non-infection)
3. Prostate cancer
4. Recent ejaculation (avoid testing PSA in 48 hours)
5. Recent prostate biopsy (avoid testing PSA in 6 weeks)
6. Recent prostate surgery
7. Recent digital rectal examination (avoid testing PSA in 1 week)
8. Recent urinary cathetherization
9. Urinary retention
10. Recent rigorous exercise esp bicycle riding

 

   Benign Prostatic Hyperplasia

Generally the cut off point for PSA value is set at 4.0ng/ml. Since PSA level is age-dependent as prostate gland will increased in size with age, some authorities suggest to modify it according to age.

Age	“Normal” PSA (ng/ml)
40-49	<2.5
50-59	<3.5
60-69	<4.5
70-79	<6.5

Although PSA <4.0ng/ml is widely considered as normal, there is still a possibility of prostate cancer (about 20% chance) in these people. PSA between 4.0 and 10.0ng/ml is considered borderline (25% chance of prostate cancer), while PSA >10.0ng/ml has higher risk (67% chance of prostate cancer).

Since the false positive rate is quite high, PSA may not be a good cancer marker as it can cause unnecessary further investigation and anxiety. Digital rectal examination (a finger is inserted into rectum) is usually done to feel for abnormality in the gland. For men with higher risk of prostate cancer such as old age and positive family history, further test such as prostate ultrasound and biopsy may be needed. For those with low risk, other causes of raised PSA should be looked for and treated accordingly. The PSA level can be repeated after 6-12 weeks to see the trend. If it continues to rise significantly, then further investigation is warranted. Another blood test that can be done is free/bound PSA ratio. More free PSA compared to bound PSA is good news. The standard PSA test is total PSA (free + bound).

Whether you should have your PSA checked depends on you. One one hand it may save your life by detecting prostate cancer early, on the other hand it may cause unnecessary anxiety, loss of money and complication from further investigation.