© The Canadian Journal of Urology™; 19(Supplement 1); October 2012
31
PSA implications and medical management of prostate cancer for the primary care physician
prostate volumes less thanor equal to 80 cc, andoneprior
negative prostate biopsy within 6 months of enrollment
(
thus representing a group at high risk for cancer on
subsequent biopsy). The primary endpoint of REDUCE
was theprevalenceof cancer on study-mandatedprostate
biopsies performed at 2 and 4 years after study entry.
Important differences between the PCPT and REDUCE
trials were principally, that patients in REDUCE were
mandated to have a negative biopsy at enrollment. In
addition, the REDUCE trial included patients with a
higher PSArange at study entry (2.5 ng/mL-10 ng/mL).
The PCPT trial, on the other hand, included patients at
lower risk (PSAless than 3 ng/mL). TheREDUCE study
demonstrated a relative risk reduction of prostate cancer
of 22.8% over 4 years. The largest reduction in cancers
was again noted in the lowgrade tumors. An increase in
high grade cancerswas also noted, but this did not reach
statistical significance (19 in the placebo arm versus 29
in the dutasteride arm, p = 0.15).
Treatment of localized prostate cancer
There are a multitude of therapeutic clinical options
currently available for patients who have early,
organ-confined prostate cancer. These include three
gold standard therapies—active surveillance (with
selective, delayed intervention, if necessary); radical
prostatectomy (retropubic, laparoscopic, or robotic);
and radiation therapy (e.g., external beamradiotherapy,
brachytherapy)—as well as other options such as
cryotherapy and high intensity focused ultrasound
(
HIFU).
Active surveillance
Active surveillance was conceived with the aim
of reducing overtreatment in patients with organ-
confined, low risk prostate cancer. This is based on
early clinical trials demonstrating that men with
well-differentiated tumors have a 20 year prostate-
cancer-specific survival rate of 80% to 90%.
18
If the
detected prostate cancer is not expected to affect overall
survival, active surveillance is a viable management
option. This implies close followupwith the option for
curative therapy upon evidence of disease progression.
It is important to differentiate active surveillance from
“
watchful waiting.” The latter is essentially deferred
treatment until the development of local or systemic
symptoms. At that point, the patient would be treated
palliatively, with local or systemic management.
Surgical management
Radical prostatectomy can be performed with open
retropubic; laparoscopic; or robotically-assisted
approaches. The main advantages of radical
prostatectomy are the possibility for a cure, the ability
for accurate pathological staging, and the possibility
of offering the patient potential salvage therapy with
radiation, if necessary.
19
An ideal candidate for radical
prostatectomy is a healthy man with a life expectancy
of at least 10 years. Preoperative clinical and pathologic
parameters are often used to attempt to identify patients
most likely to benefit from surgery.
19
The principal
disadvantages of surgery include possible urinary
incontinence and/or erectile dysfunction. However,
with improved understanding of the male pelvic floor
anatomy and improved surgical approaches, great
strides have been made in reducing adverse outcomes.
Radiation therapy
Radiotherapy is offered as either brachytherapy, external
beam radiotherapy (EBRT), or a combined approach.
Brachytherapy involves radioactive seeds that are
implanted directly into the prostate gland to deliver
high doses of radiation to the prostate while sparing
adjacent structures. EBRT uses gamma radiation beams
directed at the prostate and surrounding tissues through
multiple fields.
19
High risk patients are typically
administered a limited course of androgen deprivation
therapy prior to, during, and after EBRT.
Cryoablation and HIFU
Newer treatment options other than the above-
mentioned, gold standard treatments for localized
prostate cancer include cryoablation, and high intensity
focused ultrasound (HIFU). Cryotherapy, which
involves freezing the prostate under direct vision,
has also been studied as a salvage option in cases of
radiation failure.
19
HIFU consists of focused ultrasound
waves, which cause tissue damage by mechanical and
thermal effects.
20
HIFU is an experimental procedure
that can be used as primary therapy or as a salvage
option. The US Food and Drug Association has an
ongoing trial to determine if HIFU can be used as a
salvage option in patients who have failed primary
external beam radiation treatment for prostate cancer.
Treatment for metastatic prostate cancer
Hormone manipulation
Prostate cancer cellular growth is mediated by
testosterone and dihydrotestosterone, under the
control of the hypothalamic-pituitary axis. Release of
gonadotropin-releasing hormone by the hypothalamus
to the anterior pituitary promotes luteinizing hormone
secretion and subsequent testosterone production in
