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© The Canadian Journal of Urology™; 18(Supplement 1); April 2011
Discussion
Screening conundrum
Physicians are trained to look for disease in patients
who come to them because the patients have concerns
about their future health or have physical symptoms.
Should physicians be screening for prostate cancer in
patients who do not come with concerns or symptoms
related to potential prostate cancer?
Dr. Willett Whitmore, an icon in twentieth century
urology, described the conundrum about screening for
prostate cancer as follows: When the prostate cancer
is curable, is screening necessary? When screening
is necessary, is the prostate cancer curable? This,
unfortunately, is wherewe stand today. Prostate cancer
is a major cause of cancer mortality in NorthAmerica,
but the potential for overdiagnosis and overtreatment
is substantial. If the need for prostate cancer
screening remains controversial among urologists,
what approach for prostate cancer screening should
urologists recommend to primary care practitioners?
Many patients and physicians ask: “What is the
prostate and why do we need it?”
The prostate is an internal gland in males, which is
about the size and shape of a chestnut or walnut and
which produces 30% of seminal fluid. The prostate
is firm and both glandular and fibromuscular, and
normally, it weighs about 20 g. It surrounds the
urethra at the base of the bladder, anterior to the
rectum. The urethra passes through the prostate like
a straw through an orange. The prostatic urethra and
bladder neck act as an “internal sphincter,” to ensure
continence. In a radical prostatectomy to treat prostate
cancer, the entire prostate including the capsule and
the seminal vesicles are removed. Obstructive and
symptomatic benign prostatic hyperplasia (BPH) may
be treated by using some type of energy to enucleate
the “meat” of the prostate, but leave the capsule intact.
Prostate cancer and BPHare two significant diseases
of the prostate. Prostate cancer is very common, if
physicians look for it. Numerous autopsy studies have
confirmed that there is a significant, age-related risk
of detecting microscopic evidence of prostate cancer:
37% of men who are age 40 have microscopic evidence
of prostate cancer.
1
What are the chances that this
microscopic cancer will become clinically significant?
This is the question that needs to be answered.
A number of recent studies of nomograms to
predict prostate cancer
2
have provided an indication
of the usefulness of PSA screening tests to help detect
cancer, the advisability of treating the cancer, and the
ability to treat the cancer completely -- depending on
the Gleason grade.
Total PSA and other tests
PSA, a glycoprotein produced in the prostate ducts,
acts to liquefy the ejaculate. The concentration of
PSA is one million times higher in semen than in the
blood, since only a very small amount of PSA leaks
into the bloodstream. The concentration of PSA in
serum decreases with ejaculation and with hormonal
treatment (finasteride, dutasteride) and it increases
with significant BPH, urinary tract/prostatic infection,
prostate biopsy, or prostatic instrumentation/surgery.
PSAhas been amainstay in the diagnosis of prostate
cancer for the past 20 years. We now know that more
sensitive, “sophisticated” PSA tests are required to
identify all prostate cancers. In a review of results
from the Prostate Cancer Prevention Trial, Thompson
demonstrated that using a static threshold PSA value
was not sufficient to detect all cancers, because even
men with very low serum PSA levels could have high
grade prostate cancer.
3
This finding encouraged the development of more
sensitive and specific PSA-based tests that physicians
could use in cases where they neededmore justification
to recommend a prostate biopsy.
It is now known that increased PSA is a function of
age. The previous belief that only a PSA above 4 ng/
mL was abnormal is incorrect. In 1997, Richardson
published age-specific reference ranges for PSA.
4
Even this approach is not all encompassing.
Urologists now recommend that a biopsy is required
if a total PSA is above 4.0 ng/mL or PSA density is
above 1.5 ng/mL for a 30 cc prostate or PSA velocity
is increasing by 0.75 ng/mL or greater than a 20%
increase in 1 year or age-related PSA is greater than
3.5 ng/mL for a man in his 50s or if the ratio of free-
to-total PSA is less than 0.20.
If total PSA or PSA density or age-related PSA or
PSA velocity do not provide sufficient evidence that
a patient should undergo a prostate biopsy to look
for possible cancer, then the newest test that can be
performed is the expensive, but very sensitive prostate
cancer gene 3 (PCA3) molecular urine assay. The PCA3
score is defined as the ratio of PCA3 mRNA to PSA
mRNA times 103. This test is particularly useful to
help decide when to repeat a prostate biopsy in men
who have already had a biopsy that was negative
for cancer. Nakanishi and colleagues
5
reported that
prostate biopsies on men who had a PCA3 of less
than 25 showed that only 13% of the cancers detected
in these men would be clinically insignificant, low
grade (Gleason 6 or less), low volume (< .5 cc) prostate
cancers. When performing prostate biopsies on men
who had a PCA3 of less than 20, more than 95% of the
cancers detected would be Gleason score 7 or greater.
21
PSA and the family physician