PSA

 

Prostate Specific Antigen (PSA)

What is PSA?

PSA stands for Prostate Specific Antigen. This is something produced by cells in the prostate and its level can be measured in the blood when it is taken from a vein for analysis. PSA is used best in combination with other factors, when estimating the risk of prostate cancer being found on prostate biopsies or the severity of prostate cancer.

What is important to know about PSA?

The absolute level and rate of change of PSA are important. A raised PSA may be either transient i.e. temporary or sustained and persistent. PSA varies by as much as 33% between tests, although not usually as much. For example, if the PSA is 3 ng/ml on 1 occasion, it may go down to 2 ng/ml or even up to 4 ng/ml on another occasion without being significant. This may be just normal variation in PSA measurements.

Therefore, several readings over time (e.g. 1 per month or every 3 months) may be needed to determine if a raised PSA is genuine or due to a temporary aberration. After several readings have been made, it is possible to calculate the PSA velocity, rate of change or doubling time, which may give additional information as to the chance or severity of prostate cancer.

It is important to remember that PSA is just one factor to be considered when considering the risk or severity of prostate cancer.

What does the level of PSA indicate?

This means how low or high it is. PSA is made by cells within the prostate and so PSA levels are higher in men who have big prostates and lower in men with small prostates.

PSA levels can be consistently high for the following reasons:

  • benign (non-cancerous) enlargement of the prostate
  • prostate cancer
  • chronic inflammation (chronic prostatitis)

Transient reasons for elevations in PSA occur:

  • when the prostate is disturbed by a medical procedure (e.g. cystoscopy, prostate biopsy or prostate surgery)
  • urine or prostate infection
  • acute inflammation (acute prostatitis)
  • the sudden inability to pass urine ('acute urinary retention')
  • ejaculation in the previous 24 to 48 hours sometimes

PSA levels may also fall because of drugs:

  • drugs finasteride (Proscar, Propecia), dutasteride (Avodart)
  • hormone or steroid medications
  • antibiotics (especially when there is prostatitis present)

Sometimes, the PSA changes because of laboratory reasons e.g. different test components or kits that are used in different hospitals.

Should I be worried about my PSA?

It is of value to determine the PSA level and rate of change if knowledge of its level helps you make decision that might have an impact on your quality of life. Thus, it depends on your age, whether you have urinary (water works) symptoms that are causing bother, and whether you have any other significant health problems affecting your life. It is best to have a discussion with a doctor who understands all the nuances before having the test done.

Dr Thomas Stuttaford in the Times wrote an interesting article on PSA testing that can be read in the Times Online.

In what situations is it helpful to know the PSA?

There are three main situations when it can be helpful:

  • Prostate cancer: If you are less than 70 years old, in good general health, PSA can be used to find men who might have prostate cancer. If the level is between 2.5 and 10 ng/ml, then there is a 25% to 40% chance that prostate cancer might be present if samples (prostate biopsies) are taken from the prostate. If the PSA is more than 10 ng/ml, the chance is more than 40%. However, it is important to understand that the PSA can rise for other reasons as indicated in the previous question.
  • Urinary symptoms due to non-cancerous (benign) prostate enlargement (BPH): If you have this problem, a higher PSA may mean that the prostate is enlarged and that there is a slightly greater risk that you might stop passing urine altogether ('urinary retention') and need a catheter or TURP (an operation to remove blockage from the prostate) to improve your urinary symptoms. It is important to exclude the possibility of prostate cancer and this may mean that prostate biopsies need be taken. Treatment with drugs is less likely to be successful for long in reducing symptoms from the prostate if it is large compared to when the it is small.
  • Bony aches in men that are new, persistent and painful: Rarely, such pain can be due to spread of prostate cancer to the bones. As many people have back ache anyway, usually the cause will not be cancer. However, one should think carefully about back pain that has recently started, persistent and disturbs sleep.

There is a booklet (Adobe PDF) that can be downloaded from Cancer Backup by following this link:

What level of PSA is dangerous?

This is very controversial for reasons given above and below.

The National Institute of Excellence (NICE) has recommended the referral of every patient with a hard and irregular prostate be referred to a urologist. NICE has recommended that referral should also be made to a urologist if t the PSA is above the average for the age of the patient even with a normal feeling prostate: i.e.

Age (years)

PSA (ng/ml) threshold

50-59

3

60-69

4

70+

5

 

However, not all experts agree with this. The problem is that the average PSA for each age group includes men with prostate cancer that has not yet been detected. In addition, the higher the PSA, the less chance of cure because cancer spreads out from the prostate cancer. Many experts recommend testing for prostate cancer if the PSA level is more than 2 ng/ml or 2.5 ng/ml. However, there is a lack of consensus on this.

In a recent study (Thompson et al, 2004, New Engl J of Med) of more 18,000 men performed to evaluate how to reduce the risk of prostate cancer, the proportion of patients with cancer by PSA is shown in the table below:

PSA (ng/ml) range

Percentage of men with prostate cancer

Percentage of men with high-grade prostate cancer

<0.5

7%

1%

0.6 to 1.0

10%

1%

1.1 to 2.0

17%

2%

2.1 to 3.0

24%

5%

3.1 to 4.0

26%

7%

 

 

This may look alarming at first glance, but should be seen as one of the problems with PSA used as a test when other risk factors are not considered. Even at low levels of PSA, prostate cancer is present, although the chance of high grade (i.e. dangerous) disease is lower.

It is possible to estimate the risk of 'high-grade' cancer and any grade of prostate cancer providing you know the following:

  • PSA level in the blood
  • whether the prostate feels normal or abnormal on examination
  • whether there is prostate cancer in the family
  • if you have had negative prostate biopsies in the past
  • Race

Then go to 'Predicting Likelihood Of Cancer If A Prostate Biopsy Is Performed'. Also the prostate risk indicator offers more estimates of risk that are more accurate than PSA alone.

See this picture for a graph of the chances using age, PSA level and what the prostate feels like:

High grade prostate cancer diagram

 

The rate of change of PSA is also important and may indicate that high grade (i.e. important cancer) or risky cancer is present.

What rate of change of PSA is dangerous?

If the PSA is rising rather than staying at the same level, it can mean prostate cancer is present even at low absolute levels. If the PSA was measured every year and changed as follows from 1.00, 1.25, 1.56, 1.95 ng/ml, then the PSA is doubling every 3 years or so. This can indicate a prostate cancer is present and growing slowly.

Similarly, if the PSA rises more than 2 ng/ml in 1 year, then it is more likely that serious prostate cancer is present.

Thus, even at low absolute levels of PSA, cancer may be present and this can be detected by serial monitoring of PSA. If prostate cancer is present, the rate of change of PSA or PSA doubling time is also associated with the degree of spread of prostate cancer.

Thus, a baseline PSA when young can be helpful for the future (see ref).

Rapid increases in PSA over a short time period (weeks) can be due to infection in the urine or prostate ('prostatitis'). This is as frequent a cause for a rapid rise in PSA over a short period as prostate cancer. If there is any suggestion of infection, this should be treated first with antibiotics and then the PSA measured again.

Therefore, it is important to remember that the PSA can also change for the reasons as indicated in the question above.

What is my chance of having a high PSA?

If a 100 men aged over 50 years have a PSA test, then about 85 will have a level less than 4 ng/ml and are less likely to have prostate cancer. Fifteen men will have a PSA greater than 4 ng/ml, and about 3 of these 15 men will have prostate cancer. These numbers are slightly higher in Afro-Caribbean men and lower in men from the far east.

What does finasteride or dutasteride do to my PSA?

You should multiply your PSA value by 2 or 2.3 if you are taking a drug like finasteride (Proscar) or dutasteride (Avodart) and use this adjusted value to make decisions such as whether to have prostate biopsies or not. These drugs lower PSA and an adjustment must be made for correct interpretation.

When on these medications, most of the change in PSA is due to prostate cancer, if present, and so changes in PSA are more important.

Are there any improvements on PSA alone?

There has been much hope in the use of Free PSA also known as free/total PSA. It identifies more closely those people who might have high grade prostate cancer. It may be helpful in deciding who should or should not have a repeat biopsy of the prostate if the first biopsy was negative and there is still worry that prostate cancer might be present. It has little use if the prostate is vey large or there is prostatitis (infection/inflammation). High levels (i.e. more than 25%) are good.

It is possible to check the urine also using the PCA3 score. This determines whether there are gene associated products present that predispose to prostate cancer. See more on this on PCA3 score.

Complexed PSA may be an improvement, but this needs to be determined further and is relatively unavailable.

Using PSA as one variable in a nomogram can enhance its accuracy in predicting prostate cancer. A link to a predictive model is given above, but there are also publications of predictive methods that can be used. Some of these have been authored by M Kattan and M Garzotto. These include the use of prostate volume and PSA density. These significantly improve the accuracy with which a diagnosis of prostate cancer can be made; however, a transrectal ultrasound is necessary to calculate the prostate volume.

Current research is focused on other areas including proPSA, which is a different kind of PSA and appears to be better than free PSA. It is available for testing only in a research setting. Another test is for EPCA-2 (early prostate cancer antigen-2), which shows much promise. This is still in research and not yet available.

How can I get a PSA test done?

You can have this test performed through your general practitioner or urologist. Before the test is done, you should understand carefully the implications and limitations of the test result. A careful discussion and counselling is necessary, which should be with a knowledgeable individual.

What should I do next if my PSA is high or is rising quickly?

Don't get alarmed. There are many reasons for a high PSA other than prostate cancer as indicated above. It is important to have a discussion with your doctor or urologist quickly to make a plan. This may mean either another blood test possibly after antibiotics, biopsies of the prostate, drug treatment or no action at all.