Prostate Cancer: Interpreting the PSA Test

PSA - what is it?
PSA or Prostate Specific Antigen is a protein which is secreted into ejaculate fluid by the healthy prostate. One of its functions is to aid sperm movement. Normally, only very low levels of the enzyme are able to enter the bloodstream. However, because in cancer, the normal structure of the tissue is disrupted, considerably more PSA is able to leak into the blood stream, and for this reason, a raised level of PSA in blood (or serum) is an indicator for the presence of prostate cancer.

How good is the PSA test?
When we take any test, it is preferable to get a definite answer: "yes, you have the cancer" or "no, you don't". Unfortunately the PSA test is not that good. At best, it is an indicator of the probability or risk that you have prostate cancer. This can be very helpful, because it guides the decision about whether you should have further tests. However it does mean that the interpretation of PSA levels is not necessarily straight forward.

What conditions other than cancer cause the PSA level to rise?
The prostate typically enlarges as men get older. Because small amounts of PSA are produced by the healthy prostate, its blood level tends to rise as men grow older. This is shown in Table 1 below.
Conditions affecting the prostate other than aging and cancer can cause the PSA in the blood stream to rise. These include infection and the quite common condition of benign prostatic enlargement (BPE).
In the United States, about two thirds of older men who have a raised PSA actually have BPE, not prostate cancer z . This

Table 1 - Suggested upper limits of PSA for different age groups
Age (years)         Serum PSA (ng/ml)
40 - 49                         2.5
  50 - 59                         3.5
  60 - 69                         4.5
  70 - 79                         6.5

Note: These levels are used only as a guide for it is possible to have prostate cancer and have a PSA level in the normal range, although this is uncommon.

means that if you have a raised PSA, you do not necessarily have prostate cancer one estimate for this figure is that cancer is found in only one man in three with an abnormal PSA result. If you have a rectal examination at the same time, and it also is abnormal, you're chances of having prostate cancer are higher, however (one in two).
Other ways of measuring PSA have been developed in an effort to make the test more specific for prostate cancer. One of these is called the "free to total" PSA and is a ratio (expressed as a per cent). Much of the PSA in the blood is bound to protein, including that produced by cancer cells. But men with BPE have higher levels of free (unbound) PSA. This means that if the total PSA level is high, the free to total ratio will give an idea of whether this is due to benign disease of cancer. This test is not yet widely used in Australia.

What is a normal PSA level?
Most authorities agree that if you have a PSA greater than 4 ng/ml, you should have further investigations. Depending on your age and family history, your doctor may refer you directly to a Urologist, or may repeat the test before referring you for further investigation.
If cancer is present, the level of PSA in the blood rises as the tumour grows. This means that lower levels of PSA are found in association with small tumours which may be still confined to the prostate gland (ie. haven't spread to the lymph glands or bones). The PSA level, together with the cancerous characteristics of the tumour cells themselves (called "grade") can indicate the risk that a tumour has grown beyond the prostate itself.

How fast do cancers grow?
Most prostate cancers grow slowly. It can take 5 -10 years after the PSA rises above 2.5ng/ml, for it to "appear clinically", that is, cause symptoms4. The median survival time (period for which 50% of men survive with treatment) after the PSA starts to rise, is thought to be 10 - 17 years For this reason, a PSA which starts to rise in an older man, say 75 - 80 years, is usually not considered to be a threat. In a man just over 50, however, it should be investigated further. These figures are presented as a guide only - the outlook for anyone diagnosed with prostate cancer takes into account many clinical factors such as the nature of the tumour cells, or tumour grade, the stage of the disease, other illnesses and so on.

It is clear then, that PSA levels can mean different things at different times. Nevertheless, PSA levels are useful, because they indicate the risk of cancer in those who haven't been diagnosed with it, and may therefore indicate the need for further investigations. Typically the next step in the investigation at this stage is a biopsy (removal of prostate tissue with a needle guided by an ultrasound probe in the rectum). If you have had a PSA test, and know the result, it is important to discuss all of the factors involved with your medical adviser, to help determine your level of risk and the need for further investigation.

Other resources
Mr PHIP Series - available from your state cancer organisation - ph: 13 1120.
1. Should I be tested?
2. Interpreting the PSA test
3. After the diagnosis 
4. Monitoring after treatment
5. Hormonal treatment
6. Useful resources
7. Sexual function after treatment

Prostate Cancer Tests: the Decision is Yours. A guide for men considering having a test for prostate cancer. Anti-Cancer Council of Victoria (ACCV). A booklet which explains what to consider before taking a test. Available from ACCV: ph: 131120.

Prostate Cancer Screening: questions and answers. Commonwealth Department of Health and Family Services, 1996. Brochure.

Your Prostate, Your Choices. G. Hirst, FRACs and S. Wilde. 1999 Bantam Books. This comprehensive book explains some of the complex questions that make decisions about testing and treatment so difficult.

Prostate Cancer Screening: summary of the review. Australian Health Technology Advisory Committee (AHTAC) 1996. AGIP Catalog no 9605282. This is a summary of the evidenced-based review on prostate cancer screening. Full review also available (AGIP cat no 9605290).