The Importance of Total and Free PSA Testing
The Importance of PSA Testing
The Prostate-specific antigen or PSA test is a blood test that can be used as a measurement of prostate health. According to a March 2009 European study published in the New England Journal of Medicine (1), the PSA test is not only a valid screening test for prostate cancer but could also significantly reduces mortality from this disease in middle-aged men.
What is a PSA Test?
The PSA test was initially approved by the US Food and Drug Administration (FDA) in 1986 to track the progression of prostate cancer in individuals who have been previously diagnosed with the disease.
In 1994, the use of the PSA test together with a digital rectal exam (DRE) was approved by the FDA to test asymptomatic men for prostate cancer. Men who experience prostate symptoms will usually undergo a PSA test (with a DRE) to help a urologist determine what’s causing the problem.
Elevated Prostate Specific Antigen
Prostate-specific antigen (PSA) is a protein secreted by healthy, as well as cancerous cells in the prostate gland. A PSA test is commonly used to measure the level of this protein in someone’s blood. This test is conducted by taking a blood sample and sending it to a laboratory for analysis. PSA test results are typically recorded as nanograms of PSA per milliliter (ng/mL) of blood. In men with prostate cancer, the blood level of PSA is frequently elevated.
Although research does indicate that having an elevated PSA level does not always mean that a man has prostate cancer (2).
PSA levels may also become elevated because of benign enlargement of the prostate gland as well as prostatitis (inflammation of the prostate) due to infection. It’s crucial to emphasize that a PSA test is not a specific prostate cancer test, but it’s a critical first step in checking for the possible presence of prostate cancer.
There are other factors that could cause your PSA levels to increase (3):
- Advancing age; PSA levels tend to rise with age.
- Inflammation of the prostate gland, from either infection or some other undetermined cause.
- Benign prostatic hyperplasia (BPH); also called an enlarged prostate. A larger prostate has more cells secreting PSA, increasing the odds for an elevated PSA level.
- Prostate cells could be inflamed by a Urinary tract infection, causing PSA levels to go up.
- Ejaculation can cause a mild elevation in the PSA score, but levels return to normal after only a few days. The recommendation is that men abstain from sex for at least 48 hours before PSA testing
- Anything that might cause trauma to the prostate like; bike riding, catheter insertion into the bladder, prostate biopsy, or cystoscopy can temporarily increase PSA levels.
Conversely, some medicines (Proscar, Avodart, Propecia) (4) could lower your PSA. If you’re taking any of these medications, you should advise your doctor. A PSA level of less than 4.0 ng/mL is considered to be normal, but changes of more than 2.0 ng/mL over a year may indicate that prostate cancer is present (5).
The Significance of Free PSA
PSA circulates through the body in two ways; bound to other proteins or by itself. Unbound PSA is called free PSA. A free-PSA test will measure the percentage of unbound PSA while a PSA test is used to measure the total of free and bound PSA in the blood (6).
The free PSA is a defective variant of normal PSA that can no longer bind to other proteins and so circulates in the blood in the free form. Although the reason why is poorly understood - patients with cancer may have lower free PSA levels than those with a benign prostate condition (6).
What if the Test Shows an Elevated PSA level?
If someone who isn’t experiencing the symptoms of prostate cancer decides to take a PSA test and discovers that he has an elevated PSA level the urologist could advise him to take another PSA test to confirm the original result.
When results show that the PSA level is still elevated, the doctor could then recommend that he continue to be tested and digitally examined at regular intervals to detect changes (if any) over time (6).
When the PSA level continues to rise or if a lump is detected during a digital examination, additional tests could be prescribed to discover possible causes (7). These tests can include:
- Urine test to check for a urinary tract infection
- Transrectal ultrasound
If the doctor suspects prostate cancer is present, then a prostate biopsy may be recommended. This procedure is used to collect multiple samples of prostate tissue by inserting hollow needles into the prostate gland and then withdrawing them. Frequently, the needles will be inserted through the wall of the rectum in a procedure called a transrectal biopsy. A pathologist then studies the collected prostate tissue with a microscope. An ultrasound may also be used to view the prostate during the biopsy, although ultrasound alone can’t be used to make a prostate cancer diagnosis.
The accepted recommendation is that once a man reaches 40 years of age, he should begin having his prostate checked to establish a baseline for future monitoring. With a baseline set, the doctor can act quickly if PSA level changes indicate a potential problem (8).
Unfortunately, many men underestimate the importance of setting a PSA baseline from a younger age. Establishing your baseline PSA level means that if there is even a small change in PSA levels - your doctor can quickly begin the necessary procedures to find out what may be causing the change and commence proper treatment if it’s indicated, possibly saving your life (9).
The PSA Controversy
The PSA test is not a cancer test. The test is only used to determine the level of PSA in a man’s blood. A high PSA score may indicate the presence of prostate cancer – but there are many factors that can cause PSA levels to be elevated, from infection to resent ejaculation.
Another problem is that the PSA test also cannot distinguish between elevated PSA as a result of a benign cancer that will pose no threat in the course of a normal lifetime, or from the presence of an aggressive tumor that poses a much more immediate threat (10).
Regardless, current research still indicates that PSA is a valid and proven marker that can be used together with other variables for determining the chance that an aggressive prostate cancer is present (10).
1) SchröderFH,Hugosson J,Roobol MJ, et al.Screening and prostate cancer mortality in a randomized European study, N Engl J Med, 2009, vol. 360 13(pg. 1320-1328).
2) O'Shaughnessy M, Konety B, Warlick C. Prostate cancer screening: issues and controversies. Minnesota Medicine, August 2010.
3) Mayo Clinic Staff. PSA Test. (N.D.). https://www.mayoclinic.org/tests-procedures/psa-test/details/risks/cmc-20200313
4) Pannek J, Marks LS, Pearson JD, Rittenhouse HG, Chan DW, Shery ED, Gormley GJ, Subong EN, Kelley CA, Stoner E, Partin AW. Influence of finasteride on free and total serum prostate specific antigen levels in men with benign prostatic hyperplasia. The Journal of Urology. 1998.
5) Carter, H. Ballentine et al. “Detection of Life-Threatening Prostate Cancer With Prostate-Specific Antigen Velocity During a Window of Curability.” Journal of the National Cancer Institute 98.21 (2006): 1521–1527. PMC. Web. 24 Nov. 2017.
6) Mione R1, Barioli P, Barichello M, Zattoni F, Prayer-Galetti T, Plebani M, Aimo G, Terrone C, Manferrari F, Madeddu G, Caberlotto L, Fandella A, Pianon C, Vianello L, Gion M. Prostate cancer probability after total PSA and percent free PSA determination. Int J Biol Markers. 1998 Apr-Jun;13(2):77-86.
7) Wilt, Timothy J et al. “Prostate Cancer: Epidemiology and Screening.” Reviews in Urology 5.Suppl 6 (2003): S3–S9. Print.
8) Larsen, Signe Benzon et al. “Baseline PSA Measurements and Subsequent Prostate Cancer Risk in the Danish Diet, Cancer and Health Cohort.” European journal of cancer (Oxford, England : 1990) 49.14 (2013): 3041–3048. PMC. Web. 24 Nov. 2017.
9) Weight, Christopher J. et al. “Men (Aged 40–49 Years) With a Single Baseline Prostate-Specific Antigen Below 1.0 ng/mL Have a Very Low Long-Term Risk of Prostate Cancer: Results From a Prospectively Screened Population Cohort.” Urology 82.6 (2013): 1211–1217. PMC. Web. 24 Nov. 2017.
10) H Ballentine Carter. Differentiation of lethal and non lethal prostate cancer: PSA and PSA isoforms and kinetics. Asian Journal of Andrology. 2012 May; 14(3): 355–360.