Prostate Specific Antigen – PSA

This protein, measured via a blood test, is produced by a normal prostate gland but to a greater extent by prostate cancer cells.
It is not perfect as a normal test does not exclude prostate cancer and a raised value does not necessarily mean the individual actually have cancer. This page highlights its role and help to:

  • Screen men for a risk of prostate cancer.
  • Assess a response to treatment or lifestyle strategy.
  • Help ensure prostate cancer is not returning after primary treatments.

Screening for prostate cancer:

This the situation were PSA is most unreliable. In fact, many university and government organisations do not recommended screening using PSA because it can miss cancer in those with a normal value (false negative) and be falsely raised leading to unnecessary investigations and worry the man, his friends and family.
The upper value considered abnormal is considered to be 4 ng/ml but the the normal value depends on the age and the size of the normal gland (which most of us do not know of course). The following values are considered normal in these age groups:

  • 40 – 49 years 2.5 ng/ml
  • 50 – 59 years 3.5 ng/ml
  • 60 – 69 years 4.5 ng/ml
  • 70 – 75 years 5.5 ng/ml

A man may still have prostate cancer if his PSA is normal. Some factors which can lower the PSA include, the 5 alpha-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).

If a man has a raised PSA, particularly if marginal, it is worth considering other factors which can cause it to be elevated. Many general practitioners will consider these and repeat the test a month or so later. If still elevated above the age adjusted range he may well wish to be transferred to a specialist Urologist as there is a risk he could have cancer. The other causes of a raised blood PSA include:

  • urinary track infections
  • recent prostate biopsies
  • a large benign prostate
  • having a urinary catheter in (a tube to drain urine)
  • prostate or bladder surgery
  • prolonged cycling
  • very recent ejaculation (within 6 hours)
  • recent rectal examination

Monitoring men with known cancer

The most useful role for PSA is to monitor men’s response to interventions which could include radical treatments such a hormone therapies, surgery, radiotherapy, brachytherapy, high frequency ultrasound or the more conservative monitoring options of active surveillance or watchful waiting .  If a man is being monitored, the rate of rise or velocity of the PSA is much more important than an isolated single level. This rate of rise is commonly known as the PSA doubling time (PSAdt). The PSA-calc phone application provides a simple method of calculating the PSAdt between two time points, even if it has not actually yet doubled (the potential PSAdt).

If the PSAdt is shortening this may mean the prostate cancer is growing at a faster rate and if lengthening it is more reassuring but it must be remembered the other factors can falsely increase or decrease PSA summarised above. There are no hard and fast rules for what is considered to be a reassuring or critical PSA but as a general rule less than 10 months correlates with disease which is likely to be growing and greater than 2 years very slow growing.

Appendix (background information)

Other tests of PSA:

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 PCA3 score

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 summaries in this table:

PCA3 scoreProbability of Cancer
<514%
5 – 1926%
20 – 3437%
PCA3 scoreProbability of Cancer
35 – 4947%
50 – 10055%
>10078%

Ultra sensitive PSA

Following prostatectomy it is useful to measure really low levels of PSA which are not necessary on monitoring or following radiotherapy, brachytherapy or whilst taking hormones. This test is avialble in surgical units and can go as low as 0.001 ng/ml.

What is active surveillance

This option is an attractive for men with low risk disease because it avoids the morbidities of other radical interventions and according to large published series, the small proportion of men who died of their disease whilst on surveillance was no different than the proportion who had intervened immediately. Large published series indicate that between 25-50% of men, on active surveillance, proceeded to radical intervention with the main criteria being PSAdt shortening to less than 3 years, the grade or number of involved cores increasing on repeat biopsy.

Active surveillance involves reviewing men regularly with PSA blood tests and DRE’s. Many hospitals are also include a repeat TRUS biopsies at one year then three yearly provided PSAdt remains > 3 years. MRI’s are now being used more frequently as part of the surveillance programme especially in younger or fitter men, who will receive radical intervention if there is evidence of progression. The decision to commence active surveillance is influenced by the patient’s age, co-morbidities and lower urinary tract symptoms. Men considered for active surveillance tend to have:

  • Early stage (T1, T2b).
  • Indolent prostate cancer (Gleason 6, some Gleason 3+4, rarely Gleason 4+3).
  • Low PSA, if available long PSAdt’s.
  • Low percentage of positive cores on histological examination.

What is watchful waiting?

This is similar to active surveillance but usually men are not considered to be in a radical (curative) pathway. That said, many men in this group may live for many years being watch or taking intermittent hormonal therapies. In this situation, if the PSA starts rising significantly then hormonal therapies are started.