Prostate Specific Antigen (cont.)
Kevin C. Zorn, MD, FRCSC, FACS
Dr. Kevin Zorn is a dual-board-certified (US and Canada), minimally-invasive uro-oncology, fellowship trained urologist at the University of Chicago. His main focus of clinical and scientific interest is in the surgical treatment of renal and prostate cancer. He is also an expert in performing surgery with the DaVinci Surgical Robotic System to manage localized prostate cancer and small renal masses. Dr. Zorn studied medicine and urology at McGill University in MontrĂ©al.
Melissa Conrad Stöppler, MD
Melissa Conrad Stöppler, MD, is a U.S. board-certified Anatomic Pathologist with subspecialty training in the fields of Experimental and Molecular Pathology. Dr. Stöppler's educational background includes a BA with Highest Distinction from the University of Virginia and an MD from the University of North Carolina. She completed residency training in Anatomic Pathology at Georgetown University followed by subspecialty fellowship training in molecular diagnostics and experimental pathology.
In this Article
- Prostate specific antigen (PSA) test facts
- What is prostate specific antigen (PSA)?
- How is PSA test measured?
- What causes PSA elevation in the blood?
- What are normal results for the PSA test?
- What are age-specific reference ranges for serum PSA?
- How is PSA used for early detection of prostate cancer?
- What is the free PSA test?
- What is free/total PSA ratio?
- What is PSA velocity and PSA doubling time?
- How is PSA testing used for pretreatment staging of prostate cancer?
- How is PSA testing used in the management of prostate cancer after treatment?
- What are the limitations of the PSA test?
- What is digital rectal examination (DRE)?
- What is the PSA screening controversy?
- How should the PSA test be used for the early detection of prostate cancer?
- What is PCA3?
- What is the 4K biomarker?
What is the free PSA test?
As described earlier, most of the PSA protein released into the blood becomes attached to other blood proteins. The PSA that does not become attached is known as free PSA and can be measured. It has been observed in small published studies that the level of free PSA is decreased in men who have prostate cancer compared to those with benign conditions. The exact level depends upon which test the laboratory uses, but generally, a test result of less than 10% free PSA is suggestive of cancer. This test is most helpful when the usual PSA test level is between 4.0 ng/mL and 10.0 ng/mL. Nevertheless, free PSA testing has predominantly been used as an adjunct (additional) test along with total PSA, particularly in men who have already undergone a negative prostate biopsy and have a PSA that remains elevated. The ratio of the free/total PSA, as will be discussed in the next section, has helped avoid a second biopsy in many cases.
What is free/total PSA ratio?
Although prostate cancer cells do not produce more PSA than benign prostate tissue, the PSA produced from cancerous cells appears to escape an enzymatic processing that cleaves the bond between PSA and its binding protein. Therefore, men with prostate cancer have a greater fraction of complexed, or bound, serum PSA and a lower percentage of total PSA that is free compared with men without prostate cancer. Therefore, the free/total PSA ratio can be additionally used in clinical practice to discriminate between PSA elevation secondary to benign prostatic disease and prostate cancers. This is particularly useful for patients with a total PSA level between 4.0 and 10.0 ng/mL and a negative normal rectal exam to help the doctor to decide if a biopsy is necessary. In one study, prostate cancer was found in 56% of men with a free/total PSA less than 0.10 but in only 8% of men with free/total PSA greater than 0.25. Nevertheless, the concept of free PSA must be used with caution as several factors may influence the free/total PSA ratio such as temperature and prostate size. Furthermore, the free PSA measurement is not clinically useful for patients with total serum PSA values less than 10.0 ng/mL or in the follow-up of patients with known prostate cancer.
What is PSA velocity and PSA doubling time?
Change in PSA levels over time can be used to assess both cancer risk and aggressiveness of the particular tumor. Most urologists use these PSA metrics to help drive patient counseling and care. PSA velocity is defined as an absolute annual increase in serum PSA (ng/mL/year). PSA doubling time is defined as the exponential increase of serum PSA over time and indicates a relative change. These two measures also have a significant prognostic role in patients that have already been treated for prostate cancer (with either surgery [radical prostatectomy] or radiotherapy [external beam or brachytherapy]). However, studies have shown that using values of these PSA measures for prostate cancer diagnosis do not provide additional information compared to PSA level alone.
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