PSA
- PROSTATE SPECIFIC ANTIGEN
This is the most widely used test for detecting prostate cancer
today. It is simple to do. A small sample of blood is taken, usually from a vein
in the arm, and is tested for the presence of PSA (Prostate Specific Antigen).
This is an enzyme which was initially thought to be formed only by the prostate
gland - hence "prostate specific". This is not so and very small quantities of
the enzyme are produced by other glands - and even by women.
The laboratory
testing the blood will come back with a number, which usually reflects the level
of PSA in the blood in nanograms per millilitre (ng/ml). A nanogram is one thousand
millionth of a gram so the quantities measured are very small. The method used
to measure these minute amounts differs between the manufacturers of the testing
equipment and the results produced vary considerably. Although all manufacturers
agreed some years ago to calibrate their equipment to produce comparable results
(the Stanford Protocol), this agreement is voluntary and is not always adhered
to. It is best if you can have all tests run by the same laboratory using the
same equipment. Most laboratories will only guarantee accuracy to within 80%.
The technical description of how the test is carried out is set out at the end
of this paper - The PSA Assay -How they do it.
The scale of measurement is unlimited and PSA readings of over 1,000 ng/ml
are not unheard of - some of the men who have contributed their stories to this
site had very high readings (one was over 4,000 ng/ml). You can see them on this
Index. One reported case
(not on this site but in the PCRI Insights
Newsletter) ws about a man in the United States who had a PSA reading of 3,552
ng/ml in 1991 which climbed to 12,600 ng/ml in 1992. In 1999 his PSA was 109 ng/ml
after treatment and he was still working as a chief pilot on the world's largest
American cargo airline.
PSA
IS NOT CANCER SPECIFIC
The test
is not prostate cancer specific. An elevated PSA reading does not mean that the
man being tested has prostate cancer. This point that is often misunderstood which
gives rise to what is referred to as "PSA anxiety" with men having multiple biopsies
in an effort to find a disease which may not exist. There is a good
piece by Ralph Valle, a long time prostate cancer activist, which is worth
reading in this context.
When the PSA test was introduced in 1990 a
reading of more than 10 ng/ml was regarded as one that should be investigated
further. This figure was subsequently reduced to 4.00 ng/ml, which is regarded
as "normal" in most countries and by most medical people. In the US there is a
move to reduce the limit to 2.60 ng/ml or even to 1.25 ng/ml. On the other hand,
one leading expert physician feels that any PSA result under 12 ng/ml is not worth
being concerned about, unless there are other symptoms. Between 25% and 35% of
men with a PSA reading of between 4.00 ng/ml and 10.00 ng/ml will be found to
have prostate cancer - in the majority of cases, the elevated reading will be
due to some other cause.
If
any PSA result is between 4 and 10 ng/ml, and provided there has been no treatment,
a second test should be run - the so-called fPSA, PSA II or Free PSA test. This
doesn't mean that you don't pay for it. It refers to the amount of what is referred
to as "unbound" PSA. The
result of this test will be shown as a percentage of the total PSA measured. The
risk of cancer being present varies in inverse proportion to the percentage shown.
So the higher the percentage, the less chance that there is of the PSA being caused
by prostate cancer. A fPSA of over 25% would mean that the most likely cause of
the elevated PSA is not prostate cancer: a fPSA of under 15% is strongly correlated
with prostate cancer. There are some studies which show that the fPSA test may
be valid for readings between 2.5 ng/ml and 20 ng/ml.
A
prostate gland that is enlarged with BPH
(benign prostate hyperplasia) will also produce more PSA than a normal sized gland.
There are various formulae used to try to relate the amount of PSA
expressed to the volume of the gland.
One of the most comminly used one is to apply a factor of 0.066 to the gland volume,
the resultant figure representing the BPH component. Deduct this from the total
PSA and the balance is the 'normal' reading. This is not a very accurate
calculation, if only because it is difficult to calculate the volume olf the gland
accurately.
Important Information on PSA levels
PSA levels can be elevated by a number of causes, from infection to physical
activities. For this reason it is very important to try and establish the cause
of any elevated PSA level reported. If the PSA is below 20 ng/ml this should be
done before having a biopsy.
The most common causes of an elevated PSA
are: prostatitis (an infection of the prostate); a bladder infection; or BPH (benign
prostate hyperplasia). This last condition affects most men over 50 years of age
and is not deadly. There are various natural and pharmaceutical products that
may reduce the size of a gland and these may reduce the effect of BPH on the PSA
level, as will a TURP (Trans Urethral Resection Procedure). Any infection should
be treated before a second PSA test is carried out. Acute prostatitis can cause
the PSA levels to rise five to seven times the normal level for up to six weeks.
Both prostatitis and bladder infections are notoriously difficult to treat.
It is recommended that blood for PSA testing should be drawn as early in
the day as is convenient and preferably before eating. Constipation and weightlifting
are thought to affect PSA levels as does virtually anything that disturbs the
prostate gland might have some effect. Some of the major physical activities which
should be avoided before drawing the blood are shown below.
· DRE
(Digital Rectal Examination). Although doctors often carry out the DRE before
drawing blood, they should reverse these procedures
· Sexual activity: Ejaculation can elevate PSA levels for up to 48 hours
after it has taken place.
· Cycling or Motor Cycling: This can increase levels up to three times
for up to a week, depending on how strenuous the cycling is and it includes an
exercise bicycle
· Alcohol and Coffee: Both can irritate the prostate and should be avoided
for 48 hours prior to blood being drawn
PSA Variance
PSA levels can also vary significantly for no obvious reason. One published
study (1) shows the following data:
· 295 men were identified
who had 2 PSA readings within 90 days and who had a first reading of less than
10 ng/ml
· Only 6% had 2 identical readings,
· 64% had a second reading with a difference between - 1.0 and + 1.0 ng/ml compared
with the first.
· In 30% it was more than +/- 1.0. Of these
· 18% had a PSA difference between +/- 1.0 and +/- 2.0;
· 7% between +/- 2.0 and +/- 3.0;
· 5% of more than +/- 3.0.
· The largest PSA differences recorded were -5.3 and +7.5 ng/ml.
· In total 46% had a increase or the same PSA on second reading, 54% a decrease.
The study stated that these differences might be the result of the mixed
effect of random errors, batch inequalities, so-called "physiologic variations"
and transient effects of concomitant prostatitis. (which I take to mean that
no-one has a clue as to why there was such variance!)
It is therefore
important to have a series of PSA tests done to establish the average level before
making any treatment decision. Many men monitor their PSA levels for some years
watching for any upward trend in the numbers. The
key issue in looking at these series of numbers is the doubling time of the PSA
numbers - referred to in the PCa shorthand as PSADT. Jon Nowick has prepared a
downloadable
Excel spreadsheet that calculates odubling time and graphs PSA results. There
is more about this issue - and some interesting illustrations of just how variable
PSA readings can be in my Personal
PSA History. The
most important point is that no decision to treat should be made on the basis
of one isolated PSA reading. Elevated PSA numbers should always be checked by
having a second test in case there is an error.
The
PSA Assay - How they do it.
The commercial PSA assays use different
techniques to measure PSA. Some are immunoradiometric, some are enzyme immunoassays
and one is a chemiluminescent immunoassay.
The description of the Hybritech
Inc Tandem-R assay is representative and as follows:
The assay is a solid-phase,
two site, monoclonal antibody immunoradiometric assay. The PSA in serum binds
to a unique monoclonal antibody fixed on a plastic bead. Simultaneously, a separate
distinct epitope of the PSA molecule is detected with a second radiolabelled monoclonal
antibody. Six calibrators are used in this test at different concentrations covering
the range of the test. Radioactivity is quantitated using a gamma ray counter
and concentration is calculated from a standard reference curve using a plot of
total counts per minute versus the log of the dose (ng/ml), connecting a straight
line between each of the calibrator points.
1.
Roehrborn et al, "Variability of repeated prostate-specific antigen measurements
within less than 90 days in a well defined patient population." Urology 1996;47:55-66..
