Prostate Specific Antigen (PSA)

All men make PSA. PSA is synthesized by the epithelial cells of the prostatic acini (the individual glandular structures within the prostate - there are thousands and thousands of acini in the prostate). The normal function of the PSA enzyme is to liquefy the semen after it has been ejaculated. 

PSA normally 'leaks' from the prostate gland into the bloodstream where it can be measured with a blood test. Because PSA is made by normal prostate tissue, PSA is found in the blood of normal men and consequently an elevation in PSA alone is not capable of diagnosing prostate cancer.

Causes of increased PSA levels:

1. Prostate cancer can result in increased leak of PSA into the blood stream. This is the most serious cause of increased PSA levels

2. Benign prostatic hyperplasia (BPH). Bigger prostate = more PSA production = more leak in to the blood stream. This is the most common cause of elevations in PSA. Benign prostatic hyperplasia is the medical term for non-cancerous prostate enlargement

3. Anything which damages the barrier between the prostate gland and blood stream. Examples:

   1. Any sort of prostate surgery (e.g. TURP)

   2. Any sort of urethral instrumentation (e.g. cystoscopy or catheter)

   3. Biopsy

   4. Vigorous prostate exam

   5. Prostate infection

Different methods of measuring PSA can provide different results but the differences are rarely enough to affect clinical decision making. The various methods of measuring PSA may result in a 25% difference in the result. This sounds like a lot, but in the vast majority of men, the differences in the reported level between the different assays is a clinically insignificant 1 mcg/L or less for PSA levels under 10 mcg/L. Changes of this magnitude generally result in a 1% or less change in the absolute level of calculated risk of having prostate cancer (using the PCPT risk calculator). From a practical perspective, having a 6% risk of having prostate cancer vs. a 7% risk of prostate cancer, for example, is clinically irrelevant.

It is important to note that there is already a substantial amount of 'background random noise' in PSA measurements that results from day to day changes in the body. The consequence is that we are always looking at a rough estimate of what the level is - and to repeat the level if there is any uncertainty, especially if the PSA is high and there is nothing else to suggest an issue. Often a repeat measurement will show the PSA is lower.

The issue with differences in the PSA measurement were only an issue when the outdated approach of using 'PSA cutpoints' was used to determine if a biopsy should be done. In this outdated approach, men were treated based on 'PSA thresholds' - for example, a man was called 'normal' if the PSA was less than 4 mcg/L but 'abnormal' if the PSA level was over 4 mcg/L. Using 'PSA cutpoints' in any form, even when adjusted for age and race for example, is a poor way to assess risk. Use of PSA thresholds discards important information that help determine risk – things such as age, race, how the prostate feels and family history of prostate cancer. Every man has some risk of prostate cancer no matter how low the PSA is. PSA is just one part of the puzzle.

PSA exists in several different forms. These are measured by PSA assays in different ways.

There are different forms of PSA which may be measured:

1. Total PSA = free PSA (fPSA) + complexed PSA (cPSA)

   1. cPSA = 70-90% of the total PSA; this PSA is bound to alpha-1-antichymotrypsin and other proteins in order to prevent potentially damaging protease activity

   2. fPSA = 10-30% of the total PSA; this is found in 3 forms

      1. benign PSA (BPSA): mainly results from PSA made in the transition zone where BPH occurs

      2. intact PSA (iPSA) similar to native active PSA but is enzymatically inactive

      3. proPSA (pPSA): mainly from the peripheral zone of the prostate; most commonly assicated with prostate cancer 

Which of these is being reported on your 'PSA measurment'? The most common is total PSA. In BC, the free PSA may be measured but the other types of PSA are not.

If you look on your PSA report, you may see a note about the type of assay that was used (e.g. Hybritech Tandem-R or other). The variation between assays is generally less than 3-5% - this is a level far below one which would affect clinical decision making. The assays are all standardized to the WHO 90:10 PSA standard which uses 90% cPSA and 10% fPSA. 

There have been many attempts to refine the abililty of PSA measurements to be better at detecting prostate cancer. These have included free vs. total measurements, BPSA and proPSA. Unfortunately, these have not provided any meaningful clinical utility to using a fairly straight forward risk assessment tool such as the PCPT calculator.

Clinical Use and Interpretation of PSA

 PSA can be used and a number of different ways and it is important to define how this particular test is being applied since his interpretation can vary significantly.

1. Screening for prostate cancer

2. Surveillance for patients with known prostate cancer

3. Post-treatment monitoring: note that interpretation depends on the type of treatment

   1. Surgery

   2. Radiation

   3. Hormone ablation

   4. Other

Assessment of prostate volume and response to treatment for prostate disease

On the Web

General Prostate Cancer Web-Resources

Prostate Cancer Canada Resources

Prostate Cancer Basics: Screening and Diagnosis

Prostate Cancer Treatment Options

Prostate Cancer Post-Treatment Recovery and Side Effects

Memorial Sloan-Kettering Cancer Center in New York is an excellent resource for information on prostate cancer. Balanced, unbiased discussions of the disease, including discussion regarding some of the controversies in prostate cancer.

General Information on Cancer

UNDERSTANDING CANCER - Metrovan Urology info on the principles of diagnosis, staging, prognosis and more.

American Cancer Society

BC Cancer Agency: Good general website from the British Columbia Cancer Agency. Has contact information on locations.

National Cancer Institute: Excellent source of understandable and mainly unbiased information. Several very good brochures on every stage of prostate cancer.

National Comprehensive Cancer Network: peer-reviewed expert content/prostate cancer guidance on evidence-based cancer diagnosis and management. Best for Prostate and Kidney Cancer. The most in-depth information is located in the physician section and requires registration.