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PCU 4|2002: Peter
T Scardino, MD
Edited comments by Dr Scardino
Multimodality approach to prostate cancer
We have learned from testicular, breast and colorectal cancer
that, even with superb local therapy, multimodality treatment in
some patients is the key to cure. Therefore, it is important that
we do more studies in prostate cancer and look at this issue, carefully.
Looking back at urology over the last 25 or 30 years, the attitude
has been that hormonal therapy does not cure prostate cancer or
prolong survival. That attitude has led many in the urology community
to be skeptical about the value of adjuvant systemic hormonal therapy
trials and to argue that, not only should patients not be treated,
but also that the trials should not even be done. I think that this
is a mistake.
If we can find evidence that adjuvant hormonal therapy really
adds to the benefit of optimal local treatment, we should learn
about it and apply it, as soon as possible. I am impressed with
the bicalutamide randomized trial data, and we need to determine
if there is a survival benefit. If a trial demonstrates reduced
mortality associated with adjuvant hormonal therapy, I think this
approach will be widely adopted.
Patients’ wishes to avoid postsurgical
radiation therapy
Although its impact on survival and clinical progression is not
known, there is good evidence that radiation therapy can reduce
the risk of PSA recurrence in men with positive margins. The downsides
to radiation therapy include inconvenience, cost, a very small risk
of worse urinary control, and a significant risk of interfering
with the recovery of erectile function. In my experience, with this
risk-benefit assessment, only one out of five men will elect radiation
therapy for positive margins.
Decision-making process about adjuvant hormonal
therapy
The key questions patients should have answers to when decision-making
are: What risk does this tumor pose to me? How likely am I to have
a positive bone scan? How likely am I to develop symptoms from the
tumor? How likely am I to die from this cancer? What price do I
pay by taking these drugs? Different men will make different decisions
with this input.
If a therapy demonstrated a 30% reduction in mortality, I think
the overwhelming majority of patients would accept side-effects
and elect to receive treatment. Until we have survival data, the
decision is more of a trade-off. Our job is to give patients the
best possible information so that they can make an informed decision
about the risks and benefits of therapy.
Prostate cancer patients have an excellent early-warning system
that is almost foolproof, and it is rare for a patient to develop
a recurrence without a rising PSA. Patients may say, “This
is a good decision, but the right time for me to make it is when
my PSA rises. If I am lucky enough to be in the group whose PSA
never rises, I have safely avoided it. If I am in the group whose
PSA rises, I still have plenty of time to obtain the benefit from
early hormonal therapy.”
Endocrine therapy in men with positive lymph
nodes
The choice here is either to begin hormonal therapy after surgery,
or to wait and see what happens with the PSA. Although there have
been randomized trials suggesting prolonged survival for men treated
with early rather than late hormonal therapy, we really do not know
how early is early. I think we probably have plenty of time if patients
decide to wait until their PSA rises, but I do not know exactly.
I explain the following to patients: “If we give you hormonal
therapy now, it will prolong the time until your PSA rises and your
cancer comes back, but I do not know if it will prolong your life.”
A small study by Messing suggests it does, but there are some problems
with that study because patients either received hormonal therapy
immediately, or when the disease came back, clinically. Today with
PSA monitoring, we can start treatment somewhere between those two
points and still treat earlier. The advantage to waiting would be
two and a half years, on average, before starting hormonal therapy.The
disadvantages may be earlier progression or decreased survival,
but we do not know that. Given that discussion, about half of patients
would not want any treatment and would elect to watch their PSA
while the other half would elect adjuvant hormonal therapy.
We use nomograms to try to judge the risk of recurrence in patients.
Anytime the risk of recurrence is above 20%, I feel an obligation
to carefully inform the patient about what the recurrence might
mean, the options for treatment and when the treatment can be introduced.
Selection of hormonal therapy
Our classic hormonal therapy has been castration. Since the publication
of the Early Prostate Cancer (EPC) data, bicalutamide now seems
like a valid approach. Probably in the future, bicalutamide will
become a more common form of hormonal therapy for men electing hormonal
therapy.
When discussing hormonal therapy, I tell patients: “You
can either have your testicles removed or you can receive an injection
every month or every three months. At the beginning, we sometimes
combine the injection with a pill that blocks the side-effects from
the injection. You can also just take a pill. The options are thought
to have the same effect on the tumor.
The differences are a matter of convenience — taking a pill
compared to receiving a shot. There may be some cost differences,
depending upon what your insurance covers. The daily pill is more
likely than the shot to cause problems with breast swelling or tenderness.
But the pill may be less likely to interfere with libido or recovery
of your erections.”
Of the men electing adjuvant hormonal therapy, the majority elects
castration and few choose an antiandrogen. But, I think that is
because the data with the antiandrogens is relatively new. We are
in a changing phase, and my guess is that, in the future, this will
probably reverse, and many men will select antiandrogen therapy
because of the decreased risk of impotence. Those men will be willing
to accept an increased risk of gynecomastia and breast pain for
a decreased risk of a diminished libido and impotence.
Antiandrogen monotherapy
Although there may be a little debate, I think there is enough
data to say antiandrogen monotherapy is probably equivalent to castration
in terms of cancer control. The attraction has been less of an impact
on libido and erectile function with bicalutamide than castration.
Today, the antiandrogen regimen of choice is bicalutamide 150
mg. We have always considered it when sexual function was an important
issue for the patient. Even 10 or 15 years ago, I was treating those
patients concerned about their sexual function and not wanting medical
or surgical castration with flutamide alone for positive nodes or
an early rising PSA. In patients with sexual function, I have always
considered antiandrogens for biochemical or clinical progression
and in the adjuvant setting.
It has been the uncommon choice in the past. But I think that
with the newer data on bicalutamide’s long-term use in the
adjuvant setting, antiandrogen monotherapy will be used more in
the future.
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