Basis of the PSA test

taken from Small Gland, Big Problem 4th Edition
by Professor Roger Kirby, Health Press 2011

Cancer can be defined as the uncontrolled division of cells. Prostate cancer develops from the lining cells of the tiny glands within the prostate whose function is to manufacture PSA. Not surprisingly therefore, prostate cancer cells nearly all continue to secrete PSA. As the cancer grows, PSA levels tend to rise. Moreover, as the pre-cancer stage, prostatic intra-epithelial neoplasia (PIN, see page 31) evolves into invasive prostate cancer, the membrane surrounding the prostate may start to break down in small areas. As a consequence, the fluid in the prostate and the PSA it contains start to leak out. The PSA finds its way into the blood and so the amount of PSA in the blood starts to increase. Progressively worsening damage to the prostate makes it more leaky which, in turn, results in higher PSA levels in the blood. A normal PSA level (in a man with no prostate problems) is sometimes accepted as being below 4 ng/mL (4 nanograms per millilitre), but this rises with age so that in men over 70 a cut-off of 6.5 ng/mL is accepted (see table below). There is nothing magical about a cut-off value, however. Recent studies have shown that many men with a PSA below 4 ng/mL may, in fact, harbour small cancers. In younger men, especially, it is the rate of the rise in PSA rather than its absolute value that may be important. Current research suggests that a rise of more than 0.75 ng/mL per year may indicate the need for further investigation, although more work is needed to verify this.

Increase in accepted PSA cut-off with age
Age PSA cut-off
40-49 years 2.5 ng/mL
50-59 years 3.5 ng/mL
60-69 years 4.5 ng/mL
Over 70 years 5.5 ng/mL

PSA in the bloodstream is either free or bound to one of two proteins – antichymotrypsin and alpha macroglobulin. For reasons that are still not clear, in men with prostate cancer the amount of unbound or ‘free’ PSA is reduced. As a consequence, a reduction in the percentage of free PSA is also an early warning sign for prostate cancer. The cut-off point is usually taken as 18%; values above this suggest benign prostate enlargement, while values less than 18% increase the probability of prostate cancer being present

When doctors and journalists talk about screening for prostate cancer, they are usually referring to the potential to test every man’s PSA level at fixed intervals of time (like the smear test for women), from the age of around 50 onwards. If the test is so useful, why is it not used in this way? There are several points that have to be considered, and the pros and cons of the PSA test are summarized in the table on page 15.