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 assay 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. In any event it does not apply to so called free PSA tests or to ultra-sensitive
tests (both of these subsidiary tests are dealt with below). It is very important
to try to ensure that all tests run by the same laboratory using the same assay
equipment. That is very difficult to do because laboratories change assay methods
quite frequently, often driven by cost issues, and they rarely tell patients or
the doctors using their services of the change. In the event of an unusual change
in PSA levels it is always worth checking to see if there has been a change in
assay and, if there has to establish a new base.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.
Most
laboratories will only guarantee accuracy to within 80%. There are many reasons
for this. For one thing, it is extremely difficult to measure very precisely either
nanograms of PSA or millilitres of blood without a degree of error - think of
the variances in gas (petrol) that is delivered on a very cold morning or a hot
noon from the same pump. The dial will register the same volume of the liquid,
but you certainly won't be getting an identical amount.
The
other, and more pertinent reason is what are termed systematic errors. These arise
where, for example the instruments have not been properly calibrated, where the
assay material used is past its best 'use by' date, where the staff in the laboratory
are not properly supervised. All these things will affect the results to a greater
or lesser degree and account for some of the variances reported. Think of photographs
printed by different photo-shops before the widespread use of digital cameras
and what a variance there was in results from, say a Fuji shop or a Kodak one.
Nowdays, many people who have home inkjet photo printers are disappointed by some
of the results with the colour of the image on the computer screen being vastly
different from the printed picture. The level and quality of inks and paper can
make a difference, as can the lack of claibration of the screen.
For
this reason results should ideally be shown as a range, or with an error margin.
For example a PSA now stated to be 4.9 ng/ml is really the mid point in a range
from 3.92% to 5.88 ng/ml. Given this a second test with a level of 5.2 ng/ml should
not neccessarily be taken as an increase in levels but as a result falling within
the same range as the first test. The same logic would apply to a second result
of 4.2 ng/ml which would not neccessarily be a fall in the PSA levels.
Apart
from these variances, there are physical activities that can affect the PSA levels
in a test. The most common of these are sexual activity and manipulation of the
gland, althogh there are others, usually where the prostate gland might be placed
under pressure, such as cycling or weight lifting. There are various studies that
try to evaluate the effect of such activities. On such study in Germany found
that there were seasonal variances in PSA levels and other studies have pointed
to the possibility of certain foods and drinks also affecting results. The issue
of varinces is discussed more fully below in Important
Information on PSA levels
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) was 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. He retired in 2008.
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 commonly 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 of the gland
accurately.
Once
treatment is completed (especially where the treatment choice is surgery), an
ultrasensitive PSA test is often used. It is important to understand why there
can be variations in these test results that may have noting to do with prostate
cancer returning. This short piece - Ultra
Sensitive PSA may give a good basic understanding of the issues. Many of the
comments apply to normal PSA testing too, so it may be worthwhile to read the
piece.
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 or even longer.
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. 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,
or possibly 72 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 doubling 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 PSA - 28 Day Experiment.
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. [back].
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..
