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.
Clinical Editor's note
March 2018 - Dr Hayley Willacy draws your attention to the newly released Public Health advice for GPs dealing with asymptomatic men over 50 years, who request a PSA test. The test aims to detect localised prostate cancer when treatment can be offered that may cure cancer or extend life. It is not usually recommended for asymptomatic men with less than 10 years' life expectancy. Evidence suggests PSA screening could reduce prostate-cancer related mortality by 21%. About 3 in 4 men with a raised PSA level (≥3ng/ml) will not have cancer. The PSA test can also miss about 15% of cancers.
Conditions which may have elevated prostate specific antigen
- Acute urinary retention.
- Benign prostatic hyperplasia.
- Old age.
- Prostate cancer.
- Transurethral resection of the prostate.
- Urinary catheterisation.
The normal range is age-dependent:
PSA Cut-off Values
|40-49||2.0 nanogram/mL or higher|
|50-59||3.0 nanogram/mL or higher|
|60-69||4.0 nanogram/mL or higher|
|70 or older||5.0 nanogram/mL or higher|
|There are no age-specific reference limits for men older than 80 years of age.|
Uses of the prostate specific antigen test in prostate cancer diagnosis
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. A Cochrane review found that prostate cancer screening did not significantly decrease prostate cancer-specific mortality.
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.
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. Moreover, research is ongoing to identify prostate cancer markers with better specificity than PSA.
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.
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.
- 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. 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.
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).
Further reading and references
Macefield RC, Metcalfe C, Lane JA, et al; Impact of prostate cancer testing: an evaluation of the emotional consequences of a negative biopsy result. Br J Cancer. 2010 Apr 27102(9):1335-40. doi: 10.1038/sj.bjc.6605648. Epub 2010 Apr 6.
Gaztanaga M, Crook J; Interpreting a rising prostate-specific antigen after brachytherapy for prostate cancer. Int J Urol. 2013 Feb20(2):142-147. doi: 10.1111/j.1442-2042.2012.03120.x. Epub 2012 Aug 20.
Hill OT, Mason TJ, Schwartz SW, et al; Improving prostate cancer detection in veterans through the development of a clinical decision rule for prostate biopsy. BMC Urol. 2013 Jan 2913(1):6.
Wilt TJ; The Prostate Cancer Intervention Versus Observation Trial: VA/NCI/AHRQ Cooperative Studies Program #407 (PIVOT): design and baseline results of a randomized controlled trial comparing radical prostatectomy with watchful waiting for men with clinically localized prostate cancer. J Natl Cancer Inst Monogr. 2012 Dec2012(45):184-90. doi: 10.1093/jncimonographs/lgs041.
Davidson J et al; Benign prostatic hyperplasia: Treat or wait?, 2008 57( 7): 454-463
Advising well men aged 50 and over about the PSA test for prostate cancer: information for GPs; Public Health England (2018)
PSA - The Test; Lab Tests Online
Prostate cancer; NICE CKS, January 2011 (UK access only)
Djulbegovic M, Beyth RJ, Neuberger MM, et al; Screening for prostate cancer: systematic review and meta-analysis of randomised controlled trials. BMJ. 2010 Sep 14341:c4543. doi: 10.1136/bmj.c4543.
Ilic D, Neuberger MM, Djulbegovic M, et al; Screening for prostate cancer. Cochrane Database Syst Rev. 2013 Jan 311:CD004720. doi: 10.1002/14651858.CD004720.pub3.
Moyer VA; Screening for prostate cancer: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med. 2012 Jul 17157(2):120-34. doi: 10.7326/0003-4819-157-2-201207170-00459.
Rodriguez S, Al-Ghamdi OA, Burrows K, et al; Very Low PSA Concentrations and Deletions of the KLK3 Gene. Clin Chem. 2013 Jan59(1):234-44. doi: 10.1373/clinchem.2012.192815. Epub 2012 Nov 20.
Siddique HR, Parray A, Zhong W, et al; BMI1, Stem Cell Factor Acting as Novel Serum-biomarker for Caucasian and African-American Prostate Cancer. PLoS One. 20138(1):e52993. doi: 10.1371/journal.pone.0052993. Epub 2013 Jan 7.
Prostate cancer risk management programme: overview; Public Health England
Klotz L; Active surveillance for prostate cancer: patient selection and management. Curr Oncol. 2010 Sep17 Suppl 2:S11-7.
Payne H, Cornford P; Prostate-specific antigen: An evolving role in diagnosis, monitoring, and treatment evaluation in prostate cancer. Urol Oncol. 2010 Jan 6.
Aliasgari M, Soleimani M, Hosseini Moghaddam SM; The effect of acute urinary retention on serum prostate-specific antigen level. Urol J. 2005 Spring2(2):89-92.
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