 Home: PCU
3|2003: Laurence Klotz, MD, FRCSC
Management of the patient at high risk for progression
after surgery
If a patient is at high risk for progression after surgery — for
example, a positive surgical margin — one has to decide whether
adjuvant therapy is indicated. The difficulty is that positive
surgical margins are compatible with cure in about 50 percent of
patients, particularly if they’re micro-focal. My approach
is not to treat those patients with adjuvant therapy, but rather
to wait for a rise in PSA and then treat, based on the interval
between surgery and the rise.
If the PSA begins to rise, there are several protocols available,
such as the RTOG protocol of radiation therapy plus hormones versus
radiation alone versus hormones alone. Off-protocol, if it has
taken more than a year for the PSA to rise, I treat with radiation.
The data shows that almost all patients in whom the PSA never went
to undetectable levels — or began to rise within the first
year — have occult systemic disease, so I treat them with
androgen ablation therapy.
Management of patients with a rising PSA after
radiation therapy
For the patient with a rising PSA after radiation, there’s
a role for salvage therapy — either cryotherapy or surgery — in
a very limited number of patients. Personally, I have zero enthusiasm
for salvage prostatectomy, because I think it’s impossible
to perform that operation in a way that preserves quality of life
and results in cure often enough to justify it. We use cryotherapy
in selected patients, but for most, we offer the intermittent versus
continuous androgen suppression trial. If they’re not interested,
they go on hormones and then we negotiate whether they go on the
intermittent approach after eight months.
Androgen replacement therapy and the risk of
prostate cancer
I’m very skeptical about the safety of testosterone replacement
therapy (TRT) for men in their 40s. Prostate cancer occurs in 30
percent of men over 50, and by the age of 80, there are micro-foci
in almost everyone. We need to understand what promotes or prevents
the development of those micro-foci into clinical prostate cancer.
Testosterone drives the growth of prostate cells, so my prediction
is that if you take a large group of men and put them all on TRT,
there will be a significant increase in their risk of clinically
diagnosed prostate cancer.
I think most men on testosterone replacement are not severely
hypogonadal, rather they’re minimally hypogonadal, or they
feel hypogonadal but their levels are in the normal range. Unless
they are severely hypogonadal, I take them off testosterone therapy.
In a man with castrate levels, no one would question the use of
hormone replacement, but if he develops prostate cancer, it requires
some thought. If he’s curable, I would treat him like any
other patient — give him an appropriate local therapy for
his prostate cancer and maintain his androgen replacement.
Prostate cancer prevention trials
In prostate cancer there’s a 25-year window from inception
to progression and I’m convinced the disease is preventable.
The finasteride prostate cancer prevention trial has just about
completed its seven-year endpoint, which is repeat biopsies. Clearly
finasteride is an active agent — it’s a hormone therapy
and it shrinks the prostate. I am confident that it will result
in a decreased rate of prostate cancer diagnoses on repeat biopsy,
if only because the volume goes down. I don’t know whether
that will translate into a meaningful endpoint, like prostate cancer
mortality. It’s possible that the patients who develop prostate
cancer on finasteride — who have been exposed to a long period
of altered hormonal milieu — may have a biologically more
aggressive form of prostate cancer.
The Selenium and Vitamin E Cancer Prevention Trial (SELECT) has
a 10- to 15- year horizon for reporting, so it’ll be awhile
before we have results. I’m quite optimistic about these
agents and I think this trial, as well as the finasteride trial,
will have positive results. The other agent that looks promising
is lycopene. I firmly believe that we’re going to find a
way to prevent prostate cancer in the next 10 to 15 years.
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