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Life Extension Magazine

LE Magazine June 2003

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Reducing Prostate Cancer Deaths
Through Prevention and Early Diagnosis

by Stephen B. Strum, M.D.
Medical Oncologist Specializing in Prostate Cancer
Co-Founder and First Medical Director of the Prostate Cancer Research Institute

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Fifteen years ago, before the advent of the PSA, men were diagnosed with prostate cancer either due to abnormalities on the digital rectal exam (DRE) or due to other laboratory or radiology findings reflecting advanced cancer. The medical means to pick up smaller amounts of prostate cancer (PC) simply were not available. This is a common dilemma in the world of cancer medicine: how do you detect the disease early, before it has spread? For women, the PAP smear dramatically changed the course of medical history for those fearing a diagnosis of cancer of the cervix. The mammogram has similarly aided women in detecting breast cancer. The prostate specific antigen (PSA) and PSA dynamics (changes over time) are able to detect PC at an earlier stage than the screening tools noted above.

Deaths caused by PC can be significantly reduced through incorporation of a DRE (Digital Rectal Exam) and a simple blood test for PSA (Prostate Specific Antigen) as part of your yearly physical examination. By maintaining and monitoring a chronological record of your PSA test results, it is possible to predict the emergence of PC several years before it would normally be diagnosed.

PSA (Prostate Specific Antigen)

Tumor cells make many kinds of proteins. We have only a dozen or so commercial tests that measure these proteins. We call such tests biologic markers or biomarkers. The PSA blood test is one such biomarker. The PSA is the single most important biomarker in the history of cancer medicine. Since tumor growth is essentially exponential, with one cell dividing into two, two to four, four to eight, eight to sixteen and so on, a protein product of a tumor cell, e.g. PSA, can reflect such exponential growth in the time it takes for PSA to double (PSA doubling time or PSADT). We know that simply measuring the PSA each year using a reliable laboratory and graphing the results of the PSA can quickly alert the patient and physician to the possibility that malignancy exists.

For some bizarre reason, this incredibly inexpensive tool that can alert us to a problem with PC has not become a routine medical practice. PSA doubling can be a significant early notification that PC is present. The example below helps illustrate this concept.

Age in Years PS (ng/ml) PSA Doubling Time (PSADT)
40 0.8  
48 1.2 Approx 14 yrs
48.5 1.6 Approx 1.2 yrs

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A man gives a history of a PSA of 0.8 at the age of 40 in 1990. No real change in PSA occurs until he reaches the age of 48, when the PSA increased to 1.2 ng/ml. This is most likely to be regarded with absolutely no concern by most physicians. However, the patient's wife encourages him to repeat the PSA and six months later it is 1.6 ng/ml. This is still well within the so-called "normal" range of up to 4.0 ng/ml but with an understanding of PSA dynamics this man must be regarded as having PC until proven otherwise.

The PSA doubling time in the last six months was shortened from 14 years to 1.2 years. Between 1/90 and 1/98, his calculated PSA doubling time (PSADT) was 163.78 months or close to 14 years. Typically, PC has an average PSADT of four years at the time of diagnosis. Unfortunately for this man, his PSADT has shortened to 14.3 months between 1/98 and 7/98. This finding should trigger additional testing and closer surveillance.

Unfortunately, this is not what occurs in the vast majority of men. Today's world of medicine is still bound to absolute concepts of "normal vs. abnormal." Usually, modern medicine does not look at patterns or trends within the so-called normal ranges. This ignores the biologic expressions of disease such as PSADT or PSA velocity (the rate of increase per year of PSA).

It is suggested that each man begin PSA testing annually starting at age 40. For men with a family history of PC involving first-degree relatives (father, brother), testing should begin at the age of 35. Because breast cancer is genetically linked to PC, we also advise men with a family history of breast cancer to start PSA testing, along with annual digital examination of the prostate, at age 35.

Also monitor the PSA doubling time independent of the absolute value of the PSA. Clinical evidence suggests that the shorter the PSADT, the greater the risk for PC. A doubling time of less than 12 years usually indicates tumor growth and should be regarded as indicating that PC is present and growing until proven otherwise. If prostate cancer is present but not diagnosed, a doubling in the PSA value is essentially consistent with a doubling of tumor size. It is during this early phase of PC growth that methods of cancer detection provide the greatest chance of cure.

DRE (Digital Rectal Exam)

Figure 1.
Prostate Anatomy.
The urethra empties the bladder, then enters the prostate where it is joined by the ejaculatory ducts, which deliver sperm and seminal vesicle fluid to nourish the sperm and help liquefy the ejaculate. The urethra then exits the prostate, enters the bulb of the penis and continues through the penis to the glans penis where it ends.

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Men can easily be tested for palpable prostate abnormalities with the DRE. The DRE done carefully and gently is an easy test that yields much information. First, it gives the physician a sense of the prostate gland volume. The gland volume is important since the bigger the prostate, the more PSA the gland is entitled to make. A rule of thumb is that the prostate gland volume multiplied by 0.067 equals the amount of PSA produced by the benign prostate tissue. A 50-year old man with a normal prostate of 30 grams or cubic centimeters would therefore be entitled to make approximately two nanograms of PSA. If such a man has a PSA of 4.00, it would indicate an excess of about two nanograms of PSA and the need for further investigation to rule out PC.

In addition to estimating prostate gland volume and calculating the benign cellular contribution to the total PSA value, the DRE can also aid in finding hard nodules and/or other evidence of disease. Palpable abnormalities of the prostate gland relate to tumor volume (also called tumor burden). The DRE is therefore an additional sensor that indicates that the amount of PC has increased enough to cause a change in the physical examination; something is now able to be felt (palpable). In the years before routine testing with PSA, most prostate cancers were palpable by DRE at the time of diagnosis. Today, close to 70% of PC diagnosed in the U.S. is no longer associated with palpable disease. This is confirmatory to the value of PSA screening-allowing an earlier diagnosis of PC--before the cancer has had a chance to get bulkier and manifest itself as palpable (called T2) disease. Most men in the U.S. currently diagnosed with PC have non-palpable prostate cancer or T1 disease.

Continued on Page 2 of 3

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