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Dr. Phil's Pearls of Widsom

Updates on Urologic Topics of Interest in the Press -  Helping you become a better informed health care consumer!

Why is it important to have my PSA testing at the same place? Why do I need to know what PSA method is used?

Great questions-very insightful!  Before I answer them, let me give you a clinical scenario which I hope will help you to understand and profit from:
 
A Doctor recommends a Prostate Specific Antigen test (PSA Test) for a 55 year old man. The blood sample from the patient is tested using the TWO different PSA tests on the market. One reports a PSA value of 4.1ng/mL; the other test reports a 3.2 ng/mL.
 
According to Bernard Cook, lead scientific advisor for Beckman Coulter (one of the two companies that performs the PSA test-in this case, the PSA Hybritech® method), "that amount of difference is not due to simple biological variation or assay imprecision (machine error)". He went on further to state, "the truth of it all is that one method, and the World Health Organization (WHO) standard delivers results that are 22% LOWER than the other method."
 
That "degree of separation", if I may overuse this phrase, can have potentially dire consequences in the early detection of prostate cancer.
 
Let me further attempt to explain this by first giving you some background and a rather basic explanation of the PSA process. There are two standards used in the world market:
 
1. PSA Hybritech® Tandem-R:
In 1986 this method became the first assay approved and served as the basis for the PSA decision limits (0.0-4.0 ng/mL) that are used today.  The strength of this assay lies in its "equimolarity"; its ability to measure both the "free" PSA (PSA freely floating in the bloodstream) and the complex PSA (PSA bound to proteins). Together these represent the total PSA.
 
2. International Reference Preparation (IRP) for PSA
In 1994 at Stanford University two scientific conferences proposed a new PSA calibration. This was in response to there being a number of tests that came on the market that failed to deliver an equimolar PSA; tests results that varied in their sensitivity as well as their specificity (measures of accuracy and disease predictability).
This conference was an attempt to standardize and do away with the inaccuracies which were confusing health care providers and placing patients at risk. They proposed a new PSA calibration material containing a 90:10 mixture of complex PSA and free PSA respectively; an attempt to correct for the non-equimolar response from some of the "other" PSA assays that were in use across the world. The WHO accepted this assay as the first International Reference Preparation (IRP) for PSA.
 
Explaining the 22% gap!
The scientific team created in their 90:10 calibration method  a standard containing more protein , which when fully integrated yielded a PSA  with a different molecular weight (28,430 Daltons) when compared to the PSA Hybritech® model (34,000 Daltons). This change produced a PSA level that is 22% lower than the PSA Hybritech® method.
 
Is this really important?
In a word, YES!
Most of the big studies that healthcare providers use as a reference for their approach to detecting and treating prostate cancer were standardized to the Hybritech technique. It was the first method, used for 8 years before the WHO standard and was therefore "ingrained" in the minds of not only health professionals, but also in the psyche of the public. I am often asked by my patients and people at various social settings where healthcare issues come up as a topic of conversation, "zero -to-four is normal for PSA, right Doc?"
In addition to this, the fact remains that Urologists use the PSA to perform other tests of prostate risk behavior. They monitor over several visits PSA velocity, PSA Doubling Time, and PSA Density.
 
What is the real range?
Well that depends who you talk to. In my previous article on PSA, I explained how there are two approaches to monitoring prostate disease. The traditional approach where health providers use PSA levels of 0.0-4.0 ng/mL (Hybritech), and the more aggressive approach, favored by most urologists, utilizing a PSA level of 0.0-2.5ng/mL. This can be found at our website, www.mainurology.com.
In the context of that discussion and what approach your Urologist uses to define significant prostate risk and disease, it is even more important that we compare "apples to apples".
Complicating this further is the realization (as I pointed on in my website essay on PSA), that a single PSA value has virtually no real meaning. It is after all, NOT A CANCER TEST! It is a measure of both benign and possibly malignant behavior. A single level without historical trends doesn't mean that much. That doesn't mean you ignore your first PSA if it is elevated (using traditional PSA cutoff value of 4.0). You seek out urologic opinion!
 
 
 
 
PSA velocity
Abbreviations: PSAV
Definition: The rate of change in the PSA level over time.

Compare to PSA doubling time
Urologists and all healthcare providers should be well versed in the need to trend your PSA's over time. This will give them more information than any one single measurement. From these historical data, they can calculate the PSA velocity, which is the change in PSA over a period of time. Anywhere from 6 months to 2 years is used to look at the PSA levels. A change in PSA greater than 0.75 in the measured interval is cause for a urologic referral and prostate biopsy.
 
 
Here's an example of what I mean in the context of the two PSA methodologies:
A man is tested using the Hybritech method and has a PSA of 3.2ng/mL. One year later, he returns and gets another PSA test but this time the WHO-calibrated test is used and his PSA is 3.2ng/mL. It appears that there has been no change in his PSA, right? Wrong!
If the patient had the Hybritech PSA done at the second visit, the score would have been higher-around 4.1ng/mL. That abnormal rise in his PSA velocity (PSAV = 0.9 vs. normal at <0.75ng/mL) SHOULD have triggered a Urologic referral or, if under the care of a Urologist, an ultrasound with biopsy would have been indicated.
 
Comparisons: Hybritech vs. WHO PSA Calibration

Description
Hybritech® PSA (ng/mL)
WHO IRP PSA (ng/mL)
1 yrs increase to trigger biopsy if PSA<4.0ng/mL PSA Velocity: (aggressive)
         0.35
      0.30
1 yrs increase to trigger a biopsy: (traditional) PSA Velocity
         0.75
      0.64
1 yrs increase in PSA  cancer
         2.00
      1.60
Total PSA value to trigger biopsy (aggressive)
         2.50
      2.00
Total PSA value to trigger biopsy (traditional)
         4.00
      3.10
 
 
 

An explanation of additional PSA based tools to help in the detection and management of prostate cancer:
In addition to the PSA measurement and PSA velocity, Urologists use PSA doubling time 
PSA doubling time
Abbreviations: PSADT
Definition: The time it takes for the PSA value to double. This is used to help predict the possibility of prostate cancer spreading (metastasis) and make treatment options.
A man goes for his routine screening PSA test and it comes back at 2.0 ng/mL. He is otherwise healthy and his physician is unconcerned by the result since 2.0 is not a "high" level in most cases. But, last year his PSA level was 1.0 ng/mL and the year before it was 0.5 ng/mL.
Should these results worry him or his doctor?
Based on mounting evidence, the answer is likely "yes." In this example, a relatively low PSA level of 2.0 could be waved off as "normal." However, this man's PSA has doubled each year for two years. There is also seen here a high rate of change of PSA (as a high PSA velocity) and could likely signify a rapidly growing cancer.
An additional tool in determining the "health of your prostate" is the PSA Density
PSA density
Abbreviations: PSAD
Definition: The relationship of the PSA level to the size and weight (volume) of the prostate. PSA value is divided by the prostate size (measured by ultrasound). It is used because an elevated PSA might not arouse suspicion in a man with a very enlarged prostate. The use of PSA density to interpret PSA results is controversial because prostate cancer might be overlooked in a man with an enlarged prostate.
What do the test results mean?
Normally, a man with a large prostate gland will have a higher PSA density value than men with a smaller prostate gland, assuming neither has cancer of the prostate. The standard PSA value is often proportional to the size of the prostate gland. Men with standard PSA values that are out of proportion with the size of their prostate gland might have prostate cancer. On the other hand, a man with a very large prostate and a slightly increased standard PSA value might not have prostate cancer. A PSA density value or score of greater than roughly 0.15 suggests prostate cancer may be present. Men with PSA density scores above this number should consider additional tests. These include a prostate gland biopsy. A biopsy is a procedure to remove a small piece of tissue. The tissue can then be sent to a lab to see if it contains cancer.
To repeat my previous assertions, the PSA level by itself does not always tell the whole story.
The "take home message for you!
It is important to not only keep track of your own PSA levels over the years BUT to have knowledge of the PSA method used and to alert your doctor to any trends that you notice. Physicians see thousands of patients a year and may simply overlook the fact that your PSA has been increasing rapidly.
Information obtained for this segment of "Ask Dr. Phil" was obtained from Diagnostics Today, Beckman Coulter, and Ask.com: prostate cancer, and various web based reference sites, and Phoenix5 Prostate cancer Glossary