PROSTATE CANCER WATCHFUL WAITING
- 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. One man in the United States 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 commercial pilot on a large American cargo airline.
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 - he called it What's New, Pauline.
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.
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.
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
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
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 levels can also vary significantly for no obvious reason. One published study 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. There is more about this issue - and some interesting illustrations of just how variable PSA readings can be in my Personal PSA History.
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.
RATIONALE: MY EXPERIENCE: MY PSA : ACTIVE SURVEILLANCE : OBJECTIFIED OBSERVATION : CLIPPINGS