Prostate-specific antigen (PSA) is a protein produced by the prostate gland. Blood levels of PSA can be elevated in men with prostate cancer. For this reason, measurement of PSA in the blood has been used as a screening test for prostate cancer. However, the PSA test was initially developed only to monitor men who had a history of prostate cancer. Views about PSA screening and appropriate follow-up have been evolving.
What constitutes an elevated PSA?
No single normal level has been established. Historically, a level of 4.0 ng/mL or higher was used to justify a biopsy of the prostate (a sample of prostate tissue) to try and determine if a man has prostate cancer. However, this practice has been changing and other factors are being considered in the decision making to perform a prostate biopsy.
Also, the thinking with regard to the management of prostate cancer continues to evolve, taking into consideration the aggressiveness of the cancer as well as the volume of cancer detected on biopsy.
Does a PSA level higher than 4.0 mg/mL mean that I have prostate cancer, and can prostate cancer be excluded if my level is less than 4.0 ng/mL?
No, prostate cancer has been detected in men with levels less than 4.0 ng/mL and many men with PSA levels higher than 4.0 ng/mL do not have prostate cancer. There is no PSA level below which the risk of cancer is zero. Two men with the same PSA level may have very different risks of prostate cancer depending on other risk factors.
Factors other than prostate cancer can cause the PSA level to be higher. These include an enlarged prostate and prostate inflammation (prostatitis). Drugs known as 5-alpha reductase blockers (finasteride or dutasteride), which can be used to treat an enlarged prostate, will lower PSA levels. These factors make the PSA level difficult to interpret.
What is known is that higher levels of PSA correspond to an increased risk of prostate cancer.
So, how should an elevated PSA level be interpreted?
The PSA level by itself may be not be the most important factor of risk. Researchers have been looking at ways to improve the performance of the test by examining multiple PSA tests and measuring the rate at which the PSA level might be increasing, called PSA velocity.
They are also looking at the ratio of PSA not bound to other proteins, called fee PSA, to the total PSA value to add to risk prediction. Other tests divide the level of PSA in the blood by the volume of the transition zone (the area surrounding the urethra) to arrive at a PSA density.
If you have had a PSA screening test, your doctor may want you to have a repeat PSA test if your level is 4.0 ng/mL or above but less than 7.0 ng/ mL. This is because PSA levels can fluctuate and may also be affected by various issues such as an enlarged prostate or an inflamed prostate/prostatitis or urinary retention.
If your doctor recommends a prostate biopsy based on the results, the larger concern is interpretation of the biopsy and how it affects your management. If examination of the biopsy tissue detects a large volume of cancer cells, it can signify a more aggressive cancer.
Prostate cancer cells are graded using the Gleason score, which ranges from 2 to 10. The higher the score, the more aggressive the cancer is. Often a score of 6 or less does not require treatment, but a discussion of the biopsy result with the doctor is mandatory.
If a biopsy detects cancer, an imaging test such as a
magnetic resonance imaging (MRI),
computed tomography (CT) scan, or
radionuclide bone scan
may be done to see how far the cancer has spread, called the cancer stage.
The stage also affects the management decision. Cancer that has spread outside of the prostate’s capsule (Stage III or IV) is riskier and more aggressive than one confined to the prostate capsule (Stage I).
What does this mean for treatment?
Many prostate cancers are slow-growing and may never threaten a man’s life. Researchers have been looking for ways to identify the aggressive cancers that may need immediate treatment. Other cancers that are less aggressive may be managed safely by active surveillance or watchful waiting due to the low risk of long-term harmful effects.
Because prostate cancer treatments may cause impotence, incontinence, and altered bladder and bowel function, it may be best to treat only intermediate- or high-risk cancers. Men with low-risk prostate cancer may avoid these complications if they are managed conservatively with continued monitoring.
Prostate cancer treatments range from monitoring for low-risk disease to
removal of the prostate,
radioactive seed implantation (brachytherapy),
freezing (cryotherapy), and
depending on the stage of the cancer. Each has its own set of side effects. For patients whose cancers develop resistance to hormone therapy, several new agents have received FDA approval over the past few years, including immunotherapy (vaccine) and drugs called abiraterone and enzalutamide.
If you have an elevated PSA and cancer is detected on a biopsy and you choose monitoring instead of treatment, you will continue to have your PSA levels monitored over time. Older men with a life expectancy of less than 10 years may also be a group for whom treatment of their prostate cancer may not extend their lives.
What does an elevated PSA mean after I’ve had prostate cancer in the past?
Your PSA level will be measured regularly after you have been treated for prostate cancer. An elevated level might mean that the cancer has recurred but this is not certain. More PSA tests may be conducted along with imaging tests to determine the need for more treatment.
Simmons MN, Berglund RK, Jones JS. A practical guide to prostate cancer diagnosis and management. Cleveland Clinic Journal of Medicine 2011; 78:321-331; doi:10.3949/ccjm.78a.10104.
Jones JS, Klein E. Four no more: The ‘PSA cutoff era’ is over. Cleveland Clinic Journal of Medicine 2008; 75:30-32; doi:10.3949/ccjm.75.1.30.
National Cancer Institute. Prostate-Specific Antigen (PSA) Test. Accessed 8/27/2013.
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