Prostate Specific Antigen (PSA)

Professional Reference articles are written by UK doctors and are based on research evidence, UK and European Guidelines. They are designed for health professionals to use, so you may find the language more technical than the condition leaflets.

See also: Prostate Specific Antigen (PSA) Test written for patients

Prostate specific antigen (PSA) is a protease whose function is to break down the high molecular weight protein of the seminal coagulum into smaller polypeptides. This action results in the semen becoming more liquid. PSA is produced exclusively by epithelial prostatic cells, both benign and malignant. It is also found in the serum. Serum PSA is currently the best method of detecting localised prostatic cancer and monitoring response to treatment but it lacks specificity, as it is also increased in most patients with benign prostatic hyperplasia[1].

Causes include:

The normal range is age-dependent[3]:

PSA Cut-off Values  

Age (years)

PSA Cut-off

40-492.0 nanogram/mL or higher
50-593.0 nanogram/mL or higher
60-694.0 nanogram/mL or higher
70 or older5.0 nanogram/mL or higher
There are no age-specific reference limits for men older than 80 years of age.
  • Doctors and patients can use Decision Aids together to help choose the best course of action to take.
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The national screening debate

The issue of a national screening programme is a controversial one but there is currently little evidence to support such an initiative. A meta-analysis and systematic review in 2010 concluded that the routine use of PSA with or without digital rectal examination for the screening of prostate cancer was not supported by evidence[4]. A Cochrane review found that prostate cancer screening did not significantly decrease prostate cancer-specific mortality[5].

The United States Preventive Services Task Force (USPSTF) currently recommends against PSA testing as a screening tool for all men in the USA, regardless of age[6].

Further complications arise in the form of the KLK3 gene which encodes PSA. Mutations which lead to abnormally reduced gene expression will result in abnormally low levels of PSA and false negative results[7]. Moreover, research is ongoing to identify prostate cancer markers with better specificity than PSA[8].

Diagnosing individual patients

The Department of Health realises that there are more than economic and clinical issues to take into account when applying the national policy to individual patients. They have therefore very wisely left it to individual patients to decide, after discussion with their doctor, whether to have a PSA test. A booklet has been produced by the Department of Health to assist this discussion[9].

The patient needs to be apprised of the following points:

  • Prostate cancer is only one of several causes of a raised PSA test.
  • Because the test is nonspecific, all patients with a significantly raised PSA should have a prostate biopsy.
  • Three out of four men with a raised PSA will not have cancer cells in their biopsy.
  • 15% of men with prostate cancer have a normal PSA.
  • There is no conclusive evidence that detection of early prostate cancer leads to longer survival.
  • The test cannot distinguish between aggressive and slow-growing cancers and may detect tumours that would not otherwise become evident in the patient's lifetime.
  • The test is of most value in patients who are 'high-risk' - ie:
    • Aged above 70 years.
    • Afro-Caribbeans.
    • Patients with a positive family history.

Monitoring the effects of treatment

There is no conclusive evidence to determine the optimal treatment of localised prostate cancer and many urologists rely on rising PSA results to signal that a radical intervention (usually either chemotherapy or radiotherapy) is necessary. This is particularly appropriate for older patients with comorbidities, on the basis that they are likely to die of some other cause before a slow-growing prostate tumour has an effect on their lifespan. Such 'active monitoring' is also appropriate for any patient who wishes to avoid the side-effects of interventional management[10]. New targeted treatments for castrate-resistant prostate cancer, however, either have little effect on PSA levels or result in benign increases and monitoring in these circumstances is more problematic[11].

At the time of the test, the patient should not have:

  • An active urinary tract infection[12].
  • Ejaculated in the previous 48 hours.
  • Had a prostate biopsy in the previous six weeks.
  • Exercised vigorously in the previous 48 hours.
  • Had a recent digital rectal examination (if possible, do the blood test before the examination; otherwise, wait for one week afterwards).

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Original Author:
Dr Laurence Knott
Current Version:
Dr Colin Tidy
Peer Reviewer:
Dr Adrian Bonsall
Document ID:
3180 (v27)
Last Checked:
23 September 2016
Next Review:
22 September 2021

Disclaimer: This article is for information only and should not be used for the diagnosis or treatment of medical conditions. Patient Platform Limited has used all reasonable care in compiling the information but make no warranty as to its accuracy. Consult a doctor or other health care professional for diagnosis and treatment of medical conditions. For details see our conditions.