Wednesday, June 27, 2007

PSA - What does it measure?

To All

This is a rather long post with a lot of references to pages on my websites about PSA. It should be read by anyone who has started this prostate cancer process and those who are on line helping others with their decision making process. Every person dealing with prostate cancer should have a full understanding of the PSA as to what it is and what it isn't.

As we all know (but some never seem to get in their mind) that the PSA is not a good marker for prostate cancer - but it is about all we have so we have to use it.

For example we know that most biopsies are made when the PSA climbs over 4.0 yet we know that many prostate cancers are found with a PSA of less than 4.0. We also know that biopsies only catch cancer about 30% of the time - and the men who do not show cancer go away thinking they have no cancer. Yet we know that a biopsy is like sticking a needle in a haystack and could miss a lot more than it finds. We know men who have high PSA's and multiple biopsies and the cancer is not found. They may or may not have cancer - we just don't know. Now these decisions on the diagnosis of prostate cancer are made on the basis of PSA's - any PSA. At the same time we know there are many things that will cause the PSA to rise that have nothing to do with prostate cancer.

After we are diagnosed we watch the PSA and the slightest movement up scares us that the cancer has returned. We seem to forget at that point how inaccurate the PSA is to track our disease. We follow it like a God when in fact it may be more like a devil because it tells us so little. As we get into metastatic disease it is all we have and we do follow it closely.

But lets forget, for a moment, all of the other things that cause the PSA to go up and down and concentrate on only one thing - the use of the various assays for measuring PSA - they are a long way from being the same and even inaccurate among themselves.

PSA results vary considerably due to several factors.

The first is random lab error which is always present because nothing can be measured with 100% accuracy.

The second factor is called systematic error. These are errors that result because one lab may use a different analytical technique (assay) for reading the PSA, or a particular labs may calibrate differently.

Lastly, other events may, and do, influence the PSA level in the blood. Ejaculation, bike riding, or any manipulation of the prostate, such as a DRE, all have the tendency to raise the PSA in the blood. Furthermore, there are theories that the time of day a sample is drawn and the day within a 28 day cycle may affect the PSA level. Also, inflammation of the prostate (prostatitis) is also a frequent source of raised PSA.


The one factor we cannot control is random lab error. Periodically a survey is taken of 1000's of labs to detect their random error in measuring PSA. Identical blood samples are sent to all labs for a PSA reading. In the study available to us at this time, six samples were sent to over 2500 labs, each sample contained a blood sample of a different PSA level from about 0.2 to 19.4. The results reported be each lab were analyzed to obtain the mean reading, the standard deviation from the mean for each lab and for each PSA level (of the six different samples sent to each lab). This allowed for the determination of a 95% confidence range -- a range around the mean value reported that there is a 95% chance the real PSA value falls within (hence, 1 in 20 reported readings will be out of this range). Here is a sample of their data.

95% Confidence
Labs Low Med. High | Mean S.D. %rekSD Range
2672 10.8 19.4 34.5 | 19.67 2.14 10.9 15.39-23.95
2653 7.2 9.8 18.0 | 9.92 1.11 11.2 7.70-12.14
2689 5.3 7.3 12.8 | 7.36 0.79 10.7 5.78- 8.94
2509 2.1 3.0 4.7 | 3.03 0.33 10.8 2.37- 3.69
2504 0.6 0.7 1.5 | 0.73 0.11 14.5 0.51- 0.95
2591 0.1 0.2 0.8 | 0.24 0.10 40.2 0.04- 0.44

Remember each of these labs got the exact same sample to test and report on. They had no idea as to what it should be. Note the Range and compare them against the Mean. Just look at the last line for example the mean was 0.24 and the range was as low as 0.1 all the way to 0.8. The upper range alone is 8 times the lower range. I think that this is perhaps due to the low numbers we are dealing with and is out of line somewhat with the others but it gives you an idea of the variance.

More information on this can be found at .


Now let us look at what it does when it is applied to humans and in addition lets look at the different assays used. Here we want to concentrate on the range within an Assay and the difference between the assays.

These figures come from the study as follows:

Clin Chem. 2006 Jan;52(1):59-64. Related Articles, Links
Interchangeability of measurements of total and free prostate-specific antigen in serum with 5 frequently used assay combinations: an update.
Stephan C, Klaas M, Muller C, Schnorr D, Loening SA, Jung K.
Departments of Urology and Laboratory Medicine and Pathological Biochemistry, University Hospital Charite, Berlin, Germany.

In this study they looked at the PSA and the %Free PSA in 314 prostate cancer patients (PCa) and 282 non prostate cancer patients (NPCa) and how there blood was read by 5 different Assays. If you want to read the actual numbers you will have to get the actual study but let me give you a few of the findings:

For the PSA they found a overall range in PCa of a low of 4.98 to a high of 7.27. For NPCa they found an overall range of 2.8 to 5.03.

Within the same Assay for PCa there seems to be a difference of about 0.7 across the board. For example the same specimen was measured from 6.5 to 7.27 in one Assay. For NPCa the difference varied from about 0.6 to 1.2 in the individual Assays.

But perhaps the most upsetting is not the range in the PSA as shown above for which we are fully aware of but the range in the %free PSA. For example across all ranges the %free PSA ranged from a low of 8.07 to a high of 14.9 for those patients with prostate cancer and for those non prostate cancer patients the range was 14.4 to 25.3. In each assay the same sample was measured within 2 to 3 points. Look at these carefully and see what differences it might make in the decision making process depending on which Assay was used.

You can see yet another table showing the differences in the PSA by various Assays at

I think we will look at the %free PSA in a little different light and wonder where the Assay that was used stands in the line.

When you consider both the LAB TESTING of standardized samples and on human subjects it adds a whole new complexity of trying to understand the PSA measurement. It does make it very clear as to why one needs multiple PSA's using the same LAB and the same ASSAY before making decisions that effect your health in one way or another.

For additional reading on the PSA read: