Professional Reference articles are designed for health professionals to use. They are written by UK doctors and based on research evidence, UK and European Guidelines. You may find the PSA Test (Prostate Specific Antigen) article more useful, or one of our other health articles.
Treatment of almost all medical conditions has been affected by the COVID-19 pandemic. NICE has issued rapid update guidelines in relation to many of these. This guidance is changing frequently. Please visit https://www.nice.org.uk/covid-19 to see if there is temporary guidance issued by NICE in relation to the management of this condition, which may vary from the information given below.
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.
Causes of elevated prostate specific antigen
- Acute urinary retention.
- Benign prostatic hyperplasia.
- Old age.
- Prostate cancer.
- Transurethral resection of the prostate.
- Urinary catheterisation.
When to test for prostate-specific antigen levels
- Ensure that the man has carefully considered the benefits and limitations of PSA tests.
- Offer PSA testing to men older than 50 years of age who request a PSA test.
- Consider a PSA test in men with:
Routine screening for prostate cancer is not national policy because the benefits have not been shown to clearly outweigh the harms. PSA testing should not be offered to asymptomatic men.
Prostate-specific antigen levels
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.
Dr Sarah Jarvis, 20th December 2021
NICE update on referral threshold for PSA
The National Institute for Health and Care Excellence (NICE) has updated its guidance on suspected cancerin relation to PSA thresholds. It now recommends that doctors should consider referring people with possible symptoms of prostate cancer (any lower urinary tract symptoms, erectile dysfunction or visible haematuria), using a suspected cancer pathway referral (for an appointment within two weeks) for prostate cancer, if their PSA levels are above the threshold for their age below. It recommends that doctors should take into account the person's preferences and any comorbidities when making the decision.
- 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 Screening Committee 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. 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.
To complicate matters further, genetic factors (abnormalities of the KLK3 gene) can cause abnormally low PSA readings, resulting in false negatives in some patients.
Rather than a national screening programme therefore, a Prostate Cancer Risk Management Programme (PCRMP) has been introduced in the UK. 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.
Diagnosing individual patients
Public Health England (PHE) 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 prostate specific antigen test. PHE has produced summary information sheets for GPs and for asymptomatic men aged 50 and over in order to assist in this process[9, 10].
The patient needs to be apprised of the following points:
- 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.
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 prostate-specific antigen results to signal that a radical intervention (usually either chemotherapy or radiotherapy) is necessary. Questions have been raised about the usefulness of PSA levels in making therapeutic decisions.
Studies indicate that the effectiveness of PSA in monitoring treatment varies, and the following should be taken into account:
- Short post-treatment PSA doubling time (<3 months in this study) may be useful as a surrogate endpoint for all-cause mortality and prostate cancer-specific mortality after surgery or radiation therapy.
- A PSA reduction of 20% to 40% at three months and 30% or more at two months after initiation of chemotherapy for hormone-independent prostate cancer may be a predictive indicator for overall survival .
- A detectable PSA after radical prostatectomy has been used as an indicator of local treatment failure or metastatic disease. However, trials suggest it should not be the sole criterion on which to decide whether further treatment is indicated.
- PSA alone is less useful in monitoring the effects of radiation therapy and hormonal therapy.
Practicalities of the prostate-specific antigen test
At the time of the test, the patient should not have:
- 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.
Further reading and references
Prostate cancer: diagnosis and management; NICE Guidance (2019 - last updated December 2021)
Prostate cancer; NICE Quality Standard, June 2015 - last updated December 2021.
Thurtle DR, Greenberg DC, Lee LS, et al; Individual prognosis at diagnosis in nonmetastatic prostate cancer: Development and external validation of the PREDICT Prostate multivariable model. PLoS Med. 2019 Mar 1216(3):e1002758. doi: 10.1371/journal.pmed.1002758. eCollection 2019 Mar.
Tan GH, Nason G, Ajib K, et al; Smarter screening for prostate cancer. World J Urol. 2019 Mar 11. pii: 10.1007/s00345-019-02719-5. doi: 10.1007/s00345-019-02719-5.
Baccaglini W, Cathelineau X, Araujo Glina FP, et al; Screening: Actual trends on PSA marker. When, who, how? Arch Esp Urol. 2019 Mar72(2):98-103.
Merriel SWD, Funston G, Hamilton W; Prostate Cancer in Primary Care. Adv Ther. 2018 Sep35(9):1285-1294. doi: 10.1007/s12325-018-0766-1. Epub 2018 Aug 10.
PSA - The Test; Lab Tests Online
Prostate Cancer; NICE CKS, June 2021 (UK access only)
Suspected cancer: recognition and referral; NICE guideline (2015 - last updated October 2023)
Hamdy FC, Donovan JL, Lane JA, et al; 10-Year Outcomes after Monitoring, Surgery, or Radiotherapy for Localized Prostate Cancer. N Engl J Med. 2016 Oct 13375(15):1415-1424. doi: 10.1056/NEJMoa1606220. Epub 2016 Sep 14.
Aizer AA, Chen MH, Hattangadi J, et al; Initial management of prostate-specific antigen-detected, low-risk prostate cancer and the risk of death from prostate cancer. BJU Int. 2014 Jan113(1):43-50. doi: 10.1111/j.1464-410X.2012.11789.x. Epub 2013 Mar 8.
Rodriguez S, Al-Ghamdi OA, Guthrie PA, et al; Frequency of KLK3 gene deletions in the general population. Ann Clin Biochem. 2017 Jul54(4):472-480. doi: 10.1177/0004563216666999. Epub 2016 Aug 23.
Filella X, Fernandez-Galan E, Fernandez Bonifacio R, et al; Emerging biomarkers in the diagnosis of prostate cancer. Pharmgenomics Pers Med. 2018 May 1611:83-94. doi: 10.2147/PGPM.S136026. eCollection 2018.
Prostate cancer risk management programme: overview; Public Health England
PSA testing and prostate cancer: advice for well men aged 50 and over; Public Health England, 2016
PDQ Adult Treatment Editorial Board; PDQ Cancer Information Summaries, Prostate Cancer Treatment, 2019