Prostate specific antigen (PSA) is an enzyme secreted by prostate cells that liquefies semen to allow sperm to swim freely. PSA is present in the blood at low levels in men with healthy prostates, and is elevated in men with prostate cancer or other prostate disorders.
Why test for PSA?
Together with a prostate examination, it is used to screen for prostate cancer. However, it is not absolutely specific for prostate cancer, and can only guide us towards making a decision about whether to have a prostate biopsy. A prostate biopsy is the definitive method to diagnose prostate cancer.
PSA is also used to monitor patients who have a history of prostate cancer to see if the cancer has come back (in those who had treatment already) or progressed (in those who are under surveillance).
PSA is one of 3 variables (the other 2 are prostate examination findings and grade of prostate cancer) used to stratify prostate cancer patients according to their risks for failure of treatment or death.
What other conditions can cause a raised PSA?
Other than prostate cancer, the two most common causes of a raised PSA are benign prostatic enlargement and prostatitis (inflammation or infection of the prostate). It can also be raised for 24 hours after ejaculation and several days after catheterisation or surgery of the urinary tract. Cycling can also cause PSA to rise transiently.
What can lower PSA?
Men who are on medications such as finasteride (Proscar or Propecia) or dutasteride (Avodart) to treat benign prostatic enlargement, can have lowered PSA levels. After a year, these drugs are shown to lower PSA levels by 50% or more. Finasteride is also marketed as Propecia for baldness, and even though this is a lower dose compared to Proscar, it can also lower the PSA by about 50% after one year. Therefore, a baseline PSA level is usually done prior to patients commencing on these medications. It must be noted that a lowered PSA does not mean a lowered risk of prostate cancer.
What are the normal levels of PSA?
There is no ‘magic’ cut-off PSA level to infer if there is cancer or not. PSA levels tell us about the probability of one having cancer; the higher the PSA, the higher the chances of having prostate cancer. Various factors like benign prostatic enlargement and prostatitis (as described above) can cause the PSA to fluctuate. PSA can also vary somewhat from laboratory to laboratory. Hence, a patient should always try to stick to one laboratory when having PSA tests. Consequently, one abnormal PSA level does not always indicate the need for a prostate biopsy.
In the past, a cut-off number of PSA > 4 was suggested as abnormal. However, a large study found that prostate cancer was diagnosed in 15.2% of men with a PSA of < 4. The dilemma is that if this threshold level is lowered to detect more cancers, more patients will risk undergoing unnecessary investigations. Expert opinions are still divided on what the best PSA threshold should be.
There are some methods that are used to improve a PSA reading, in the hope that it can help differentiate between benign and cancerous causes and also between slow-growing and aggressive prostate cancer. Some of these methods are:
Age-specific PSA reference range
Because PSA tends to rise with age, an age-specific PSA reference range was proposed.
- Age 40 – 49: normal PSA <2.5.
- Age 50 – 59: normal PSA <3.5.
- Age 60 – 69: normal PSA <4.5.
- Age 70 – 79: normal PSA <6.5.
There are concerns that the original study (Osterling et al, 1993) was done primarily on white men, and did not consider racial or ethnic backgrounds. It may also lead to missing or delaying the detection of prostate cancer in as many as 20% of men in their 60s and 60% of men in their 70s.
PSA velocity looks at the change in PSA level over time. PSA should rise faster in men with prostate cancer than in those without cancer. A PSA rise of > 0.75 ng/mL per year is predictive of prostate cancer.
PSA density is calculated from dividing the PSA level by the prostate volume. Because larger prostates also produce more PSA, a raised PSA level might not arouse suspicion if a man has a very large prostate. Therefore, PSA density takes into account the relative PSA contributions of benign prostatic tissue and prostate cancer. Comparing two men with equally large prostates, the man with cancer will have an even more elevated PSA than the man without cancer. A PSA density of > 0.15 suggests prostate cancer may be present.
Free to total PSA ratio
PSA circulates in the blood in two forms: free or bound to a protein molecule. The total PSA is the sum of the free and bound forms. Benign conditions like benign prostatic enlargement produce more free PSA while cancer produces more of the bound form. Therefore, the lower the free-to-total PSA ratio is, the more likely cancer is present. This test is more accurate in those with a PSA between 4.0 – 10.0 ng/mL.
Should everyone be screened with PSA?
Prostate cancer is a complex disease; it can develop into a fatal, painful disease, but it can also develop so slowly that it will never cause problems during the man's lifetime. There are concerns regarding the mass use of PSA and over-detection of incidental, small-volume and low-grade prostate cancer with little potential to cause harm to the patient. A prostate biopsy can cause harmful side effects such as bleeding and infection. Even if the prostate biopsy is negative, the PSA still has to be monitored regularly and this can cause psychological stress on the patient. Prostate cancer treatments, such as surgery and radiation therapy, may cause incontinence, erection problems and other complications. Therefore, the risks and benefits of diagnostic procedures and treatments must be taken into account when considering whether to have prostate cancer screening.
Based on a recent large European study (ERSPC trial), there was a reduced risk (27%) of prostate cancer death with PSA testing and treatment in those patients in the 55 ‐ 69 year age group after 9 years. This benefit is likely to increase as these patients are followed up for a longer time. Subgroup analyses from this trial indicate that PSA screening may have little effect in men > 70 years of age.
An individualised strategy for screening should be done according to a patient’s risk factors.
Should I get my PSA done?
The following recommendations are meant to act as a guide and by no means should replace an individual consultation and discussion with your doctor. Each patient is different and brings his own unique factors into the discussion.
In those between 50 – 70 years old:
A yearly PSA test is recommended from the age of 50 to 70 years old, with the caveat that you must discuss with your doctor the risks and benefits of the test and the implications of a positive result. Even though the ERSPC trial showed a survival benefit in screening men in this age group, 48 men needed to be treated for each life saved suggesting a significant over‐treatment effect.
In those > 70 years old
If you have no symptoms, the benefit of PSA screening is reduced because it is likely that you may die of other medical problems than prostate cancer. However, if you are fit and healthy and have a life expectancy of > 10 years, then a PSA test can be considered. If you have symptoms suggestive of advanced prostate cancer, your doctor will do a PSA test to look for it.
In those < 50 years old
If you have risk factors for developing prostate cancer, a PSA test is recommended from an earlier age after a discussion with your doctor.
- >45 years in those with a positive family history.
- >45 years in those from high-risk ethnicities (e.g., African Americans).
- >40 years in those carrying BRCA2 gene mutations.
What if the screening test shows that my PSA is elevated?
Other factors must be considered to assess your overall risk of prostate cancer:
- Is the prostate examination abnormal too?
- Are there any risk factors for prostate cancer?
- Do you have any symptoms suggestive of the other causes for a raised PSA (e.g., benign prostatic enlargement, prostatitis, bladder infection)?
Some other tests may be done to help assess your overall risk:
- A urine test to check for urinary tract infection or blood in the urine.
- Ultrasound of the urinary tract can check for prostate size and how well you empty your bladder (optional).
- A free-to-total PSA ratio, or a PSA density can be done to improve a PSA reading.
- An MRI of the prostate. This has been MBS listed in Australia since July 2018.
If you have no symptoms to suggest cancer is present, your doctor may choose to:
- Repeat your PSA and watch the PSA velocity.
- If you have symptoms of prostatitis or a bladder infection, you may be given a course of antibiotics and then asked to repeat the PSA after that.
If cancer is suspected, a prostate biopsy is needed to look for cancer. During the biopsy, some samples of the prostate tissue are taken and viewed by a pathologist under the microscope to look for cancer cells.
Do all men with prostate cancer have to be treated?
Some men have early prostate cancer (low volume, low grade, low PSA, favourable prostate examination findings) and are deemed to have low risks of prostate cancer causing significant problems. These men can be offered active surveillance, during which they can defer definitive treatment and avoid the side effects of those treatments. These men have regular PSA monitoring and prostate examinations, and may have repeat prostate biopsies later to look for progression of the cancer.
What if there is a raised PSA after treatment for prostate cancer?
This usually indicates that there is a recurrence of prostate cancer. For men who had a radical prostatectomy (surgical removal of the prostate), additional treatment may be needed if:
- Their PSA does not fall to undetectable levels after surgery.
- After having no detectable PSA, their PSA level increases on two or more subsequent measurements.
For men who had radiotherapy, additional treatment may be needed if their PSA has risen by 2 ng/mL or more after having a very low PSA level.
A PSMA PET / CT scan can be useful to detect any spread of cancer to the rest of the body.
Read about the Australian PSA testing for prostate cancer guidelines:
Download Prostate specific antigen testing for prostate cancer - PDF (120 Kb)