PROSTATE CANCER WITH A NORMAL PSA
Some 15-20 per cent of men with a normal total PSA (tPSA) of 4 ng/ml or less can have clinically significant prostate cancer.
These men have no symptoms and usually no findings on examination.
The only way these men can be identified is by calculating their per cent free PSA (%freePSA) which is determined from their tPSA and free PSA levels ( free PSA divided by tPSA X 100 = % free PSA).
The free PSA is so called as it is not bound to a carrier protein in the blood. However, the tPSA is bound to a protein called
alpha1 antichymotrypsin while the free PSA is unbound in the blood or, somewhat to alpha 2 macroglobulin.
Unfortunately, most physicians and screening studies do not make use of the %free PSA estimation so a good number of men have their prostate cancer undetected due to the MISTAKEN belief that all is well if the tPSA is 4 ng/ml or less.
The use of the %free PSA was approved initially only for men with a total PSA of between 4-10 ng/ml in the belief that if one could identify more accurately those men who could benefit from a prostate biopsy we could minimize the number of men having unnecessary biopsies.
However, the real value of the %free PSA is in identifying those men that have an increased probability of prostate cancer before the PSA is significantly elevated. Ideally, the %free PSA level should be greater than 25 and the lower the level of the %free PSA (converse of tPSA level where the higher levels suggest greater risk) the greater the probability of prostate cancer.
Some studies have shown that with tPSA’s of between 2.6-4 ng/ml and using the cutoff %free PSA of 19% that a prostate cancer detection rate of about 90% was achieved.
In my practice however, I advise men to consider a prostate biopsy who have a tPSA of 1.6 ng/ml or greater but with a
persistently abnormal %free PSA of 19 or less.
Early detection of prostate cancer by using the %free PSA is critical in identifying more men with organ confined disease.
Early detection,especially when the tPSA is under 4 ng/ml may increase the chance of a cure particularly with a minimally invasive option such as HIFU.
Importantly, one should not act on one abnormal laboratory value but have it repeated so as not to act on spurious lab results.
The tPSA blood test may be incorrect if the specimen has not been handled by the lab properly or has been assayed without proper calibration of the equipment. Also, the free PSA is affected by renal function leading to a false %free PSA estimation in those men with renal dysfunction. Furthermore, both tPSA and free PSA increase with age, after prostate examination, after biopsy, ejaculation and after a urinary tract infection but will normalize with time. Proscar and other medications reduce both tPSA and free PSA and can engender a false sense of security. Lowering the PSA in this way may not have a protective benefit.
Finally, nothing is absolute and no marker or MRI diagnoses prostate cancer. These studies may suggest a prostate cancer and having your %free PSA determined and repeated if necessary, can lead too an important prostate biopsy and an early jump on your prostate cancer if identified.