Prostate Specific Antigen (PSA)

What is PSA?

Prostate Specific Antigen (PSA) is an enzyme which is naturally produced by the prostate gland in all men. The function of this enzyme is to liquefy semen after it has been ejaculated so that sperm can swim toward the egg; semen has a very high concentration of PSA. PSA is produced by epithelial cells within the prostate gland. Some of the PSA which is produced by the prostate leaks into the blood stream; it is the level of PSA in the bloodstream (serum PSA level) which is measured by laboratories and is of interest to physicians.

What affects PSA levels?

Several conditions other than prostate cancer can cause an elevation in PSA levels outside of the age-specific range. An age specific range is often used when interpreting PSA levels because as men grow older their prostate glands grow larger (Benign Prostatic Hyperplasia- BPH) and accordingly produce more PSA. Thus, an older man may be considered to have a normal PSA level when the same level in a younger man would be considered abnormal See table 1.

PSA elevation outside of the age-specific range can occur in men with larger prostates than average (BPH), prostate infection and inflammation, prostate trauma (for instance recent insertion of a urethral catheter or flexible cystoscopy) and prostate cancer. Temporary, mild elevations can also occur within 24 hours of ejaculation.

Day to day variations in PSA also occur; these variations can be up to 30% of the baseline value.

Enhancing the Performance of PSA:

1. Free versus attached PSA

PSA circulates in the blood in two forms: free or attached to a protein molecule. Free PSA may help tell what kind of prostate problem a man has. With benign prostate conditions (such as BPH), there is more free PSA, while cancer produces more of the attached form. If a man’s attached PSA is high but his free PSA is not, the presence of cancer is more likely. In this case, more testing, such as prostate biopsy, may be done.

2. PSA Velocity

The rate of change of PSA over time (PSA velocity) is also related to the risk of having prostate cancer. We know that the prostate gland grows slowly as we age; correspondingly the PSA level increases slowly. If a cancer is present the PSA increases faster than if BPH only is present. Several PSA values obtained three to six monthly over at least twelve months are needed in order to calculate an accurate PSA velocity.

If the PSA velocity exceeds 0.75 ng/mL per year then, even if the PSA level is in the normal range a biopsy should be considered.

Using the PSA Test

The PSA test is useful in screening for prostate cancer, staging the disease and monitoring the response to treatment of prostate cancer.

1. Screening and Early Detection using PSA

Early detection and treatment of prostate cancer improves the chance of successful curative therapy such as surgical removal of the prostate or prostate radiotherapy.

Screening for prostate cancer should begin at age 50 (40 if there is a family history) and be performed every 1-2 years; screening should stop once a mans life expectancy is less than ten years which is generally in the eighth decade of life.

Screening involves both a PSA blood test and a finger examination of the prostate gland (Digital Rectal Examination or DRE). During a DRE, a doctor inserts a gloved finger into the rectum and feels the prostate gland through the rectal wall to check for lumps. If either of these examinations are abnormal then consideration needs to be given to referral to a urologist for a prostate biopsy.

Screening for prostate cancer is controversial. Interim evidence from non-mature randomized population based trials of screening in both the USA and Europe suggest that there is likely to be a survival advantage for screening. We will have to wait several more years until these large trials mature and report their results before we can be certain that screening for prostate cancer leads to an increase in survival.

An abnormal PSA test does not prove that prostate cancer is present; a biopsy is needed to diagnose prostate cancer. The likelihood of a positive biopsy depends upon a mans age, family history of prostate cancer, PSA level and DRE findings. These factors can be entered into a computer program available on the National Cancer Institute website to give an estimate of the risk of a positive biopsy. Cancer Risk Calculator at COMPASS (Comprehensive Center for the Advancement of Scientific Strategies)

2. Staging utilising PSA

Once prostate cancer has been diagnosed it is important then to ‘stage’ the disease. The stage of a cancer refers to how advanced the cancer is at the time of diagnosis and relates directly to the most appropriate treatment and the chance of successful cure (prognosis). The serum PSA level is a reflection of tumour volume and this in turn relates to the chance of prostate cancer cells having spread outside of the prostate gland.

Other important information relevant to the stage of the prostate cancer is obtained from the DRE, the pathologists examination of the biopsy specimen, and often also from radiological examinations such as a bone scan, Computed Tomography (CT) or Magnetic Resonance Imaging (MRI) scan.

3. Monitoring after treatment using PSA

After treatment for prostate cancer the PSA level should fall.

1. Radical Prostatectomy: Following radical prostatectomy, the PSA level should fall to a non-detectable level within 2-4 weeks providing successful removal of all cancer and benign prostatic tissue has been achieved. Following surgery the PSA level is checked at three months and then every six months for the first two years and thereafter annually. If the PSA becomes detectable again after surgery this usually indicates that there is residual prostate cancer present. This cancer may be at the site of prostate removal (prostate bed), termed a local recurrence; outside of the prostatic bed in lymph nodes or bones (termed a systemic recurrence); or both a local and systemic recurrence. Determination of whether the relapse is just local or systemic is difficult. The likelihood of either scenario can be estimated by looking at the pattern of PSA recurrence; i.e. an early and rapid PSA recurrence tends to suggest a systemic relapse. If the relapse is thought to be local only then consideration is often given to delivering a course of radiotherapy to the prostate bed to eliminate the remaining cancer cells.
2. Radiation Therapy: Following radiation therapy (external beam or seed brachytherapy) the fall in PSA is far slower than that following surgery. Usually the PSA takes at least eighteen months to reach its lowest point. The PSA will always be detectable following radiotherapy and there may be transient PSA elevations (PSA bounce) in the first few years following radiotherapy. The lower the level of PSA that is achieved the lower the chance of future disease relapse.
3. Castration: Castration refers to the therapeutic reduction of a mans testosterone level to nearly zero. Testosterone is produced by the testicles and its presence is critical for the continued growth of prostate cancer. Castration results in temporary remission of prostate cancer and is the standard treatment for men with metastatic prostate cancer.
   Castrate levels of testosterone can be achieved in one of two ways:
   1. Surgical removal of the testicles.
   2. Injection of a drug every 1-6 months.
   Following castration the PSA level often falls rapidly. The ultimate level that the PSA reaches is predictive of the future behaviour of the cancer. After several years the cancer may begin to grow and produce more PSA in spite of castrate levels of testosterone; this is termed castrate resistant prostate cancer (CRPC). The development of CRPC indicates that symptoms from the cancer are likely to arise and that the overall prognosis from the disease is less favourable.
   Temporary suppression of testosterone levels prior to, during, and after radiotherapy is also commonly performed. This improves the chance of cure of the cancer with radiotherapy.

This fact sheet complements the discussion during your consultation, which will apply your individual circumstances to the above facts.