PSA (prostate specific antigen) exists in the blood in three main forms:

• Free PSA, which is not attached to any other proteins
• Bound PSA which is attached to another protein. These proteins may be either :
• a-antichymotrypsin. (This accounts for the majority of PSA circulating in the blood stream). Or
• a-2 macroglobulin.

The normal tests measuring PSA levels in the blood cannot detect PSA that is bound to a2 macroglobulin, and so gives the total of the free PSA and the PSA bound to a-antichymotrypsin.

Studies have shown that in men with prostate cancer the level of free PSA is less than in men who do not have cancer. So it has been suggested that measuring the ratio of free PSA to the total PSA concentration could help in deciding whether small increases in the PSA level in the blood are due to benign (non-cancerous) prostate disease or prostate cancer.

At the present time, however, there are variations between the different methods available for measuring PSA and uncertainty over what value for the 'free to total' ratio clearly indicates the presence of a cancer. This means that this test is not routinely used in the diagnosis of prostate disease and it is only really appropriate to use it when the PSA level is borderline, although it may become more valuable in the future.