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© The Canadian Journal of Urology™; 18(Supplement 1); April 2011
22
Since the standard (total) PSA test and the digital
rectal examination (DRE) are the most widely
available tests, they were the basis for prostate cancer
screening/detection in two very large prostate cancer
screening studies -- the European Randomized Study
of Screening for Prostate Cancer (ERSPC)
6
and the
Prostate, Lung, Colorectal andOvarian Cancer (PLCO)
trial in America.
7
The American study has been criticized because it
was “contaminated” with too many patients who had
alreadyhadat least one serumPSAtest prior to enrolling
in the study. This created a selection bias because men
who had been found to have a high PSA were not
included. Both studies, however, demonstrated that
huge numbers of men had to be “screened” in order
to prevent one death from prostate cancer.
Active surveillance
Today, urologists are concerned about finding many
men with minimal disease who may not require
therapy, but have endured the potential risks of
a prostate biopsy. For a number of years, many
urologists have advocated “active surveillance” for
patients with low risk prostate cancer. Most studies
show that a man with a PSA of less than 10 ng/mL
who has a biopsy that shows three or fewer positive
cores (where not more than 50% of any one core has
cancer) has only about a 35% chance of having his
cancer progress to the point where intervention is
either recommended by the physician or demanded
by the patient.
8
With active surveillance, a patient has a PSAtest and
a DRE every 3 months and has a repeat biopsy usually
1 year after the initial biopsy and then every 2 years.
8
Often, the physician uses a PSAvalue as a trigger for a
“for cause” biopsy. Ideally, the biopsywill only identify
high risk patients with Gleason score of 6, or Gleason
scores of 7 or higher, which should be treated.
Men who are at high risk of having prostate cancer
detected include those who are older, have a family
history of prostate cancer, have high testosterone
levels, are of African ancestry, have a high-fat diet or
are obese or inactive, or have an abnormal DRE.
New screening guidelines
There are now new guidelines for the “not at risk”
male. TheAmericanUrologicalAssociation’s Prostate-
SpecificAntigen Best-Practice statement (revised 2009)
contains an algorithm that suggests that a baseline PSA
determination should be done when a patient is 40
years old.
9
If the result is normal for the patient’s age
(eg < 0.7 ng/mLat age 40), then the test can be repeated
every 5 years. If at age 50, the patient’s PSA is still
below 2.0 ng/mL, then repeating the PSA test every
2 years would prevent the physician from missing a
clinically significant cancer.
Similarly, the American Cancer Society suggests
annual screening starting at age 50.
10
All groups
seem to agree that PSA is still a valid tool in helping
to diagnose clinically significant prostate cancer
early, when it is still curable. For a discussion of the
management of localized prostate cancer, see the
How I Do It article on HIFU published recently in
The
Canadian Journal of Urology
.
11
Hormonal deprivation (reducing the production or
uptake of testosterone either centrally or peripherally)
as a management strategy for non-operable or other
stage of prostate cancer has been utilized since the
40s. There are numerous medications available for
this approach.
12
Medical therapies for prostate cancer
There have been a few newly approved medical
therapies for the management of prostate cancer.
The luteinizing hormone-releasing hormone (LHRH)
antagonist degarelix (Firmagon) was recently approved
inCanada. This drug acts at the hypothalamic-pituitary
axis, but in contrast to LHRH analogs, because it is a
competitive inhibitor at androgen receptors, it causes
an almost immediate and complete reduction of
testosterone production in the body, with no “flare”
(rise) in the production of testosterone for the first
month, which can be seen with the LHRH analogs.
“At risk” individuals treated with LHRH analogs are
pretreated with 1 month of an antiandrogen such as
bicalutamide (Casodex) to prevent uptake of the added
“flared” testosterone that could stimulate the exploding
of potential bony metastases in the spine. Firmagon
may also prevent “micro flares” of testosterone rise at
the end of the 3 month cycle, which may occur with
other agents. Lastly, the drug is believed to prevent
the rise of follicle-stimulating hormone (FSH), so it
may protect a patient from developing hypogonadal-
induced osteoporosis.
Triptorelin (Trelstar) is the newest LHRH analog,
which promises better, more reliable suppression
of testosterone over the whole course of the depot
injection. It is given intramuscularly, with a smaller
needle than that used for other preparations.
Denosumab is a new receptor activator of nuclear
factor kappa B (RANK) ligand inhibitor, which may
help prevent bone mineral loss and skeletal-related
events that have been associated with long term
hormonal manipulation in prostate cancer patients.
BARKIN