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Prostate Health
Stephen A. Sacks, MD, FACS PSA (prostate specific antigen) is an enzyme produced only by the glands inside the prostate and not by the majority of prostate tissue which consisits of muscle and collagen. Significant increases in blood levels of PSA (serum PSA) are frequently found in men with prostate cancer; but elevations in serum PSA may occur as a consequence of benign enlargement of the prostate gland (BPH), inflammation (prostatitis), and injury to the prostate gland. Moreover, approximately 25% to 30% of men with prostate cancer will have "normal" PSAs. PSA is specific for the prostate gland, but not for prostate cancer. History Another enzyme called Acid Phosphatase was found to be elevated in blood samples of men with advanced prostate cancer as early as 1938, although this substance was not specific for the prostate gland. One of the types of Acid Phospatase more closely related to the prostate gland recognized as Prostate Acid Phosphatase (PAP) appears to be more consistently elevated in men with prostate cancer which has spread (metastasized) to bone. "PSA" is much more important than "PAP" in the diagnosis and treatment to prostate cancer. In 197l, Japanese scientists discovered a protein substance in seminal fluid which they termed "gamma-seminoprotein," and by 1979 this enzyme was confirmed by a team of American investigators to be specific for the prostate gland, hence prostate specific antigen (PSA). In 1990, it was reported that the total amount of PSA found in the circulation actuary consisted of two fractions, a "free" form (free PSA), and a form that was linked to other substances (bound PSA). It was further observed that as the percent of "free" PSA decreased, the incidences of prostate cancer increased. Application The advent of standardized PSA testing has revolutionized the ability of urologists to diagnose and treat men with prostate cancer. In conjunction with digital rectal examination (DRE), an annual PSA determination is generally recommended for all men over the age of 50, and for African-American men and other men who may have a famfly history (either side) of prostate cancer. (father, brother, uncle or grandfather) and who are over 40 years of age. Despite the impressive yield (about twice as effective as mammography) of these combined analyses, considerable efforts are underway to improve and refine the information suggested by PSA testing. That "PSA" is by no means the ideal test to detect prostate cancer is documented by the observation that approximately one-third of men who have prostate cancer have "normal" PSAs, and approximately two-thirds of men with "abnormal" PSAs do not have prostate cancer. There have been four primary attempts to enhance the specificity of PSA determinations: PSA density, PSA velocity, age-related PSA and fractionated PSA. PSA density expresses the PSA blood level divided by the size (volume) of the prostate gland. A very large prostate gland associated with a moderate PSA elevation would result in a relatively "low" PSA density. Alternatively, a small prostate gland associated with an elevated PSA would translate into a "high" PSA density and would be significantly more suspicious. PSA velocity expresses the change in PSA over time based upon the notion that prostate cancer will elaborate more PSA over time than benign growth. This is an important concept that may validate the observation that an unexplained progressive increase in the PSA may be of more concern than an elevated but stable PSA. Age-related PSA determinations have been suggested as a means of expressing PSA per decade of a man's life. These adjustments have been offered to compensate for the laboratory "normal" values which were initially determined in men all under the age of 50. That PSA increases with age may be compounded by the increasing incidences of both benign and malignant growth of the prostate. The upper limit of "normal" PSAs related to age are: 40 to 49 = 2.5, 50 to 59 = 3.5, 60 to 69 = 4.5 and 79 to 79 = 6.5. The age-related upper limits for Afiican American men appear to be increased by one unit per decade. Fractionated PSA expresses PSA as a ratio of the "free" to the "total" determinations. PSA is identified in the circulation either linked to other substances or in a form that is unattached or "free". For reasons which are unknown, significantly lower percentages of free PSA are associated with higher incidences of prostate cancer, and higher percentages of free PSA are associated with lower incidences of prostate cancer. These ratios are particularly useful when the percentages are significantly above or below the 14% cutoff point. Summary PSA does not fulfill all of the requirements of an ideal tumor marker, being neither an absolute indicator of prostate cancer or even of disease related to the prostate gland. While the availability of PSA tests has been of great value to the urologist in diagnosing and treating prostate cancer, recent advances in the understanding of the biology of PSA will result in additional clinically useful information. |
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What is Urology?