Prostate specific antigen, PSA, PSA doubling time, Free versus bound PSA

Prostate specific antigen is a protein which is produced by the normal gland and to a greater extent cancer cells. The normal blood range for PSA, depends on age. A normal test does not exclude prostate cancer. The upper value considered abnormal is now considered to be 4 ng/ml.

                                40 - 49 years 2.5 ng/ml,
                                50 - 59 years 3.5 ng.ml,
                                60 - 69 years 4.5 ng/ml,
                                70 - 75 years 6.5 ng/ml

The basic PSA blood test is particularly used to [1] detect cancer and [2] to assess the response to treatment. Any man with a PSA above this age adjusted range may well wish to be transferred to a specialist Urologist as there is a risk he could have cancer although there are other causes of a raised blood PSA:-

infections
recent prostate biopsies
having a urinary catheter in (a tube to drain urine)
prostate or bladder surgery
prolonged exercise, such as long-distance running or cycling
ejaculation
some drugs

Some drugs may also reduce the PSA level, the most well known of these are called 5alpha-reductase inhibitors. These drugs reduce the metabolism of the male hormone testosterone into active metabolites. They are given to reduce the size of a benign (non-cancerous) prostate and improve the water flow. The two most commonly prescribed are Finasteride (Proscar) and Dutasteride (Adodart). There are ways to make the PSA more reliable, if needed:-

Free versus bound PSA

The PSA circulates in the blood in two forms - the free form and the form bound to a protein. Some laboratory, as well as an absolute level provide the ratio of free versus bound. The benign condtions which elevate the PSA mentioned above produce more free form whilst cancer produces more bound form. Therefore, the greater the ratio (ie more free form) to more likely that it is benign (not cancer)

The PSA doubling time (PSA velocity)

This is the time it take the the blood PSA to double. In many cases it hasn't actually doubled but the potential doubling time can be estimated by the following calculation:-

PSA_a x t

PSA_b - PSA_a

Where PSA_a is the first value PSA_b is the second value and t is the time between them. (E.G a PSA increases from 2 to 3 over 3 months the PSAdt = 2/1 x 3 = 6 months). The PSAdt is much more accurate and sensitive to progression and prognosis that a single value. For example, a trial published by Fowler in 1995 showed that if the PSADT was < 10 months, there is a high probability of metastatic disease.

There is a new genetic test that determines whether products of genes associated with prostate cancer are present in the urine. It is useful when the PSA level is low or there is doubt whether a rise relates to cancer or inflammation. This test is not widely available can be requested in some private clinics. Men are examined rectally to massage the prostate they then produce a urine sample which is sent for analysis. The results are presented in a series of percentages:

PCA3 Score                Probability of cancer
<5                                14%
5-19                             26%
20-34                           37%
35-49                           47%
50-100                         55%
>100                            78%

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