Prostate specific antigen

What is prostate specific antigen (PSA)?

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 by epithelial prostatic cells, both benign and malignant.

It is also found in the serum. Serum prostate specific antigen 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 of elevated prostate specific antigen²

Causes include:

• Acute urinary retention.

• Benign prostatic hyperplasia.

• Old age.

• Prostatitis.

• Prostate cancer.

• Transurethral resection of the prostate.

• Urinary catheterisation.

When to test for prostate-specific antigen levels ³⁴⁵

• PSA should be checked if there is a suspicion of prostate cancer. This may be because of symptoms that could be due to advanced prostate cancer - eg, lower back pain, bone pain, unintentional weight loss. Most men with early prostate cancer are asymptomatic.

• The National institute for Health and Care Excellence (NICE) CKS also recommends that we consider testing in men with erectile dysfunction or visible haematuria, (without urinary tract infection) particularly if aged over 45..

• For men who have lower urinary tract symptoms, testing is advised if their symptoms are suggestive of benign prostatic enlargement, the prostate feels abnormal on digital rectal examination, or they are concerned about prostate cancer.

• Screening for asymptomatic men is discussed in detail below and not covered in this section.

• Offer PSA testing to men older than 50 years of age who request a PSA test.

Prostate-specific antigen levels³

The upper level of normal for prostate-specific antigen (PSA) level varies according to age and race, and the PSA test is not diagnostic. Within the normal range for a given age group, there is a low risk of prostate cancer. Therefore refer only if there are other concerns - eg, abnormal digital rectal examination.

Clinical judgement should be used to manage symptomatic men and those aged under 50 who are considered to have a higher risk for prostate cancer.

The most recent update of the NICE guidance on suspected cancer suggests referral on an urgent suspected cancer pathway at the following levels for each age group:

• Under 40 - use clinical judgement.

• 40 to 49 - above 2.5 mcg/L.

• 50 to 59 - above 3.5 mcg/L.

• 60 to 69 - above 4.5 mcg/L.

• 70 to 79 - above 6.5 mcg/L.

• Above 79 - use clinical judgement.

Uses of the prostate-specific antigen test in prostate cancer diagnosis

The national screening debate

A 2015 review by the UK National Screening Committee (NSC) concluded that despite the likelihood that a national screening programme would reduce mortality by at least 21%, the widespread use of prostate specific antigen in asymptomatic men who had not had a digital rectal examination would increase the risks of over-diagnosing and overtreating clinically insignificant prostate cancers.

Men with indolent disease would unnecessarily be exposed to the side-effects of radical treatment, including sexual dysfunction and urinary problems. There is also, in extreme cases, the risk of death.

This position has been confirmed by the ProtecT trial, which demonstrated that there was no difference in 10-year survival rates between men with low-risk localised prostate cancer who were allocated to active surveillance and those who chose radical treatment.⁶ This was supported by the CAP trial of UK general practices, the findings of which did not support single PSA testing for population-based screening.⁷

To complicate matters further, genetic factors (abnormalities of the KLK3 gene) can cause abnormally low PSA readings, resulting in false negatives in some patients.⁸

Rather than a national screening programme therefore, a Prostate Cancer Risk Management Programme (PCRMP) was introduced in the UK in 2016. The aim is to provide enough information to primary healthcare professionals to assist asymptomatic men aged 50 and over to make an informed choice about whether or not to have a PSA test.

It is hoped that research into emerging biomarkers will eventually result in the PSA test being replaced by more accurate investigations.⁹

In November 2025 the NSC published a draft updated recommendation and opened a consultation on its review of updated evidence. The draft recommendation is as follows:

• Offer a targeted national prostate cancer screening programme to men with confirmed BRCA1 or BRCA2 gene variants every 2 years, from age 45 to age 61.

• Not recommend population screening.

• Not recommend targeted screening of Black men or of those with a family history of prostate cancer.

• To collaborate with the Transform trial to answer outstanding questions on the effectiveness of screening for Black men and those with a family history and to await the development of a more accurate test than PSA alone.

The consultation period closes in February 2026, with a final updated recommendation due in March 2026.

Screening individual asymptomatic patients¹⁰

As discussed above, there is insufficient evidence for population level screening and there is therefore no resourced screening service in the UK. The NHS website says that men aged 50 or over can approach their GP for a PSA test, but there is no national funding in place to cover this work which remains unresourced in the absence of any local enhanced service schemes.

Information sheets for GPs and for asymptomatic men aged 50 and over are available, which cover some of the following information.¹¹ In reality, GPs are unlikely to have time to give this information verbally when an asymptomatic patient requests a PSA test - the usual practice would be to give a leaflet and a blood form and to advise the patient that if they still want to have their PSA checked after reading the leaflet then they should go for the blood test and proactively check the result with the practice or via online access to their records. If after reading the leaflet they change their mind, the blood form can be discarded.

• Prostate cancer is only one of several causes of a raised PSA test.

• Three out of four men with a raised PSA level will not have cancer cells in their biopsy. Therefore, having the test may lead to unnecessary worry and exposure to the risks of further investigations. The most common problems after biopsy are infection and bleeding. However, if they do not have the test they will have an increased risk of presenting only when they have symptoms, which can increase the chance of prostate cancer remaining undiagnosed until it is advanced and incurable.

• 15% of men with prostate cancer have a normal PSA. Normal results can be falsely reassuring. However, men who do not have the test will miss the chance of early diagnosis and treatment.

• 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.

• Potential treatments can include surgery, radiotherapy, and hormone therapy. Side-effects can include problems with erections, loss of fertility, and incontinence. Not having the PSA test will mean that treatment will not be required unless symptoms develop, so these risks will be avoided. However, the patient will miss the chance of early detection, as outlined above.

Screening after a raised PSA with no cancer diagnosis ¹²

A 2024 publication by GIRFT (Getting It Right First Time) recommends that men who are referred with a high PSA but do not have prostate cancer should have PSA surveillance in primary care, with the frequency of this varying depending on their risk stratification. This is not contractually part of core general practice and should therefore be funded by an enhanced service which covers the costs; if no such enhanced service is in place then GPs are entitled to reject this additional work and insist that the specialist team requests such tests as they deem necessary.

Practicalities of the prostate-specific antigen test

At the time of the test, the patient should not have:³

• An active urinary tract infection.

• 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).

• Had receptive anal intercourse for 48 hours before a PSA test - this is an essential requirement for gay, bisexual, and other men who have sex with men.

The specimen should reach the laboratory within 16 hours.