Andrew Siegel MD 5/4/19
Above photo is of the famous Mannekin Pis statue in Brussels
Last week’s entry discussed the basics of PSA—”PSA 101” if you will. Today is the “300-level course” that reviews refinements in PSA testing that make the test more valuable, meaningful and predictive.
What are some of the refinements and nuances in PSA (Prostate Specific Antigen) testing?
PSA Velocity: Comparing one’s PSA values year-to-year is most informative. Generally, PSA will increase by only a small increment, reflecting benign prostate growth associated with the aging process. If PSA accelerates faster than anticipated—a condition known as accelerated PSA velocity—further evaluation is indicated. The bottom line is that an isolated PSA (out of context) is much less meaningful than a series of one’s PSAs over time.
Please note: Many labs use a PSA of 4.0 as a cutoff for abnormal, so it is possible that one can be falsely lulled into the impression that their PSA is normal. For example, if one’s PSA is 1.0 and a year later it is 3.0, it is still considered a “normal” PSA (because it is less than 4.0) even though it has tripled (highly suspicious for a problem) and mandates further investigation. So, it is worthwhile knowing your actual PSA level, similar to being aware of your cholesterol level.
PSA Density: The larger the prostate, the more PSA that is manufactured. PSA density (PSA divided by prostate volume) is the PSA level corrected to prostate size. The prostate volume can be determined by imaging studies including ultrasound or MRI. PSA elevations are less worrisome under the circumstance of an enlarged prostate.
A PSA density > 0.15 is concerning for prostate cancer.
Free PSA: PSA circulates in the blood in two forms: a “free” form in which the PSA is unbound, and a “complex” PSA in which the PSA is bound to a protein. The free PSA/total PSA ratio can offer a predictive value (similar to how HDL cholesterol/total cholesterol can be helpful in a person with an elevated cholesterol level). The higher the free to total PSA ratio, the greater the chance that benign enlargement of the prostate is the underlying source of the PSA elevation.
In men with a PSA ranging from 4-10, the probability of cancer is:
9-16% if the free/total PSA ratio is greater than 25%
18-30% if the ratio is 19-25%
27-41% if the ratio is 11-18%
49-65% if the ratio is less than 10%
4Kscore test: The 4Kscore Test is a refinement that measures the blood content of four different prostate-derived proteins: total PSA, free PSA, intact PSA and human kallikrein 2. Levels of these biomarkers are combined with a patient’s age, DRE (digital rectal examination) status (abnormal DRE vs. normal DRE), and history of prior biopsy status (prior prostate biopsy vs. no prior prostate biopsy). These factors are processed using an algorithm to calculate the risk of finding a Gleason score 7 or higher (aggressive) prostate cancer if a prostate biopsy were to be performed. The test can increase the accuracy of prostate cancer diagnosis, particularly in its most aggressive forms. (It cannot be used if a patient has received a DRE in the previous 4 days, nor can it be used if one has been on Avodart (dutasteride) or Proscar (finasteride) within the previous six months. Additionally, it cannot be used in patients that have within the previous six months undergone any procedure to treat symptomatic prostate enlargement or any invasive urologic procedure that may be associated with a PSA elevation.)
How is PSA used in men diagnosed with and treated for prostate cancer?
PSA is unquestionably the best marker to gauge prostate cancer status in the follow-up of men who have been treated for prostate cancer by any means or in those men who are on active surveillance.
After surgical removal of the prostate gland for cancer the PSA should be undetectable and after radiation therapy the PSA should decline substantially to a reading of usually less than 1.0. Rising PSA levels after treatment may be the first sign of cancer recurrence. Such a “biochemical” relapse typically precedes a “clinical” relapse by months or years. If a man on active surveillance has consecutive substantial elevations in PSA level, it signals the possibility of more aggressive disease that may require active intervention.
Is PSA the definitive test for prostate cancer?
No! PSA is the definitive test for monitoring prostate cancer and a good, but imperfect screening test since the PSA can be elevated in the absence of prostate cancer and low in the presence of prostate cancer.
An elevated or accelerated PSA, abnormal digital rectal exam and suspicious MRI are all helpful tests, but remember that the definitive and conclusive test for prostate cancer is the ultrasound-guided prostate biopsy.
“The buck stops here” with prostate biopsy, the conclusive test for prostate cancer.
Wishing you the best of health,
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Dr. Andrew Siegel is a physician and urological surgeon who is board-certified in urology as well as in female pelvic medicine and reconstructive surgery. He is an Assistant Clinical Professor of Surgery at the Rutgers-New Jersey Medical School and is a Castle Connolly Top Doctor New York Metro Area, Inside Jersey Top Doctor and Inside Jersey Top Doctor for Women’s Health. His mission is to “bridge the gap” between the public and the medical community. He is a urologist at New Jersey Urology, the largest urology practice in the United States.
The content of this entry is excerpted from his new book, PROSTATE CANCER 20/20: A Practical Guide to Understanding Management Options for Patients and Their Families
Video trailer for Prostate Cancer 20/20
Preview of Prostate Cancer 20/20
Andrew Siegel MD Amazon author page
Prostate Cancer 20/20 on Apple iBooks
Dr. Siegel’s other books:
PROMISCUOUS EATING— Understanding and Ending Our Self-Destructive Relationship with Food
MALE PELVIC FITNESS: Optimizing Sexual and Urinary Health
THE KEGEL FIX: Recharging Female Pelvic, Sexual, and Urinary Health
Tags: 4K score, Andrew Siegel MD, free PSA, Prostate Cancer 20/20, prostate specific antigen, PSA, PSA density, PSA velocity
Our Greatest Wealth Is Health 
May 6, 2019 at 9:05 AM |
Off topic: Would you please write about prostate massage and whether it has legitimate medical benefits.
July 30, 2019 at 12:32 PM |
would be a good topic
January 14, 2023 at 5:35 AM |
[…] Since it reduces prostate specific antigen (PSA) by 50%, if the PSA is not appropriately reduced, it can spell trouble and point to the possibility […]
December 16, 2023 at 6:15 AM |
[…] PSA (prostate specific antigen) – a simple blood test – is an essential means of screening for and monitoring prostate cancer. It is important to know that certain medications may affect PSA level, some increasing PSA level while others decreasing PSA level. Knowledge of whether or not you are using one or more of these medications is important with respect to the interpretation of your PSA, which needs to be put in the appropriate context. […]