Home: PCU
1|2003: Gerald W Chodak, MD
Edited comments by Dr Chodak
Reserving lymph node dissection for patients at
high risk
I don’t believe we should do lymph node dissection unless
the probability of lymph node metastases is significant. Peter Carroll
published a mathematical decision analysis several years ago in
which it was determined that unless the risk of lymph node metastases
was greater than 15%, it wasn’t worthwhile to remove the lymph
nodes. More than 80% of patients diagnosed today have less than
a 10% probability of lymph node metastases, and they can be spared
lymph node dissection. There is a small, but real, complication
rate. It prolongs the surgery, increases the cost, and in a low-risk
subset of patients, the chance of benefit is small.
We still have no proof that removing lymph nodes involved with
cancer improves survival. To me, it is a diagnostic test that tells
us whether to proceed with prostatectomy. In a high-risk patient
— a man with a PSA over 10, Gleason score of 7 or higher and
a palpable tumor — I would ask the patient before going to
the operating room what he would like to do if there is cancer in
the lymph nodes. I generally remove the lymph nodes, do a frozen
section and only proceed with prostatectomy if the results are negative.
But, the patient has to make the decision because I cannot tell
him for sure that there is no benefit from prostatectomy. I can
only say there is no scientific proof of a benefit. If he wants
to be very aggressive and do the prostatectomy anyway, I would not
even do a frozen section.
Early endocrine therapy in men with positive
lymph nodes
I am guided by two randomized trials. Ed Messing did a study in
men who had radical prostatectomy, who were randomized to receive
either early or late hormone therapy, showing a survival benefit
for early hormone therapy. Although there are some valid criticisms
of that study, it is the only randomized trial addressing this question.
A study by Granfors looked at men who had a lymph node dissection
and received radiation with or without supplemental hormone therapy.
This study also showed a significant survival benefit in the group
receiving the combination of radiation and hormones. Neither study
tells us whether or not local therapy was beneficial, but both trials
support the concept that earlier hormone therapy in the face of
lymph node metastases improves survival compared to delayed therapy.
If I do a lymph node dissection and find positive nodes, I recommend
that the patient receive hormone therapy.
Bicalutamide 150 mg versus castration in non-metastatic
disease
In a study of men with metastatic prostate cancer, bicalutamide
was inferior by about 42 days in average survival compared to castration.
However, in patients with non-metastatic disease, there was no significant
survival difference between castration and bicalutamide. I think
that offering bicalutamide is reasonable in these patients, particularly
those who are concerned with libido and sexual function. Men undergoing
castration are far more likely to be impotent and have problems
with their libido than those receiving bicalutamide.
Endocrine therapy in patients with PSA relapse
In counseling patients regarding antiandrogens versus castration,
the conversation centers on the side-effect profiles. Bicalutamide
is associated with better libido and better sexual function, but
therapy is associated with breast tenderness and enlargement. Patients
undergoing castration have hot flashes, sexual dysfunction and decreased
sex drive, weight gain and decreased energy.
In terms of comparing efficacy, there’s just not enough
data to answer that question. I am very careful to let science drive
the information and not just give my gut feeling. To the best of
our information available, one could extrapolate and say that, “I
think that there may not be a difference,” but we do not know
for sure.
Treatment of high-risk patients after local therapy
As we treat patients earlier, the side effects go on for a longer
and longer period of time. For example, in patients undergoing castration,
we are increasingly worried about bone de-mineralization and fractures.
There is also some question about whether castration has a deleterious
effect on mentation. As we use these therapies for longer periods
of time, we may run into added side effects that we’re not
completely aware of.
With regard to efficacy, I tell these patients that there is a
potential to delay progression with both castration and bicalutamide,
but comparing them isn’t easy. We don’t have any scientific
data to guide us; therefore, we have to make a philosophical choice
whether to be conservative or aggressive. Patients usually have
a general feeling about how aggressive they want to be. If they
are fearful of dying of their disease and want to do everything
possible to decrease that probability, then you take an aggressive
approach, which includes hormone therapy — whether it’s
castration or an antiandrogen — and possibly radiation therapy.
Informing patients about specific risks and benefits
of treatments
It is important to be sure that patients choose therapy based
on the information that we have available. Every patient needs to
know the status of our knowledge in terms of his chance of recurrence,
his chance of benefiting from a therapy and the chance of having
a side effect.
If we talk about local therapy, patients should be given the complication
rates of the doctor treating them rather than the complication rates
across the country. We keep data on outcomes that we relay back
to patients. I can say, “In my practice in your age group,
here are the complications and here are the probabilities of benefiting
from the treatment.”
Impact of earlier endocrine treatment on mortality
We started using PSA extensively for screening in about 1990.
Prostate cancer mortality began declining in about 1993. Many people
believe that screening is the cause for the change, but the long
natural history of prostate cancer would make it very difficult
for a mortality reduction to occur so soon after PSA testing began.
The disease just doesn’t progress that rapidly. So, we need
a better explanation.
What’s a better explanation? I believe it is earlier hormone
therapy. Over the last 10 years since the development of PSA, we
are alerted to people progressing after primary therapy much earlier
than ever before. Many of these patients went on hormone therapy
before they developed metastatic disease, when there were fewer
hormone-independent cells. There were more cells capable of responding
to the primary hormone therapy. Although those people weren’t
cured, they did have a delay in disease progression and death.
Selecting patients for maximum androgen blockade
I believe that maximum androgen blockade (MAB) remains an option
for patients with metastatic disease. The meta-analysis has flaws
that preclude a clear conclusion that you shouldn’t use MAB,
and I think there is a subset of patients who may receive a significant
benefit. Other men may derive little or no benefit. We can’t
select which patients fall into each group; therefore, I believe
that it is an option for the patient who wants to be aggressive.
There is scientific data that supports it in terms of improving
survival, but there is a
Approaching decision-making with the prostate
cancer patient
It is important to review the side effects and the probability
of experiencing those side effects for the treatment options that
are available. I then attempt to understand how important it is
for that patient to avoid a specific side effect, and that discussion
helps guide their therapy.
It is really a matter of first obtaining a sense of what they’re
willing to accept, and then trying to offset that with the gain
they are likely to receive from the therapy. If I can’t tell
them that they’re going to live longer, what can I tell them?
Oftentimes, there is a lot of missing information, and patients
have to struggle with the uncertainty. They have to understand that
there is not a clear direction, and that it isn’t possible
for me to make the choice for them.
Importance of presenting patients with information
Even if we as physicians don’t agree with a treatment, we
have an obligation to present randomized study information to patients.
We must consider the implications if several years from now a patient
progresses and finds out there was a treatment you never even discussed
with them. If there is no randomized trial data, it becomes more
equivocal, but if there is a randomized study addressing a particular
clinical situation, I think we are obligated to share that information
with our patients.
Patients know that a rising PSA is a bad thing, and preventing
that is clearly their goal. A rising PSA is psychologically traumatic
even though it doesn’t m
ean they’re going to die or suffer from their cancer. Patients
select primary therapy because they want to avoid progression, and
that continues along every step of the way. The difference is the
price they’re willing to pay for that. Depending on their
age and their quality of life, they may trade off differently at
different times in their life.
You ultimately want your patient to feel that you gave them the
best information and did the best thing for them. Although you can’t
guarantee they’re going to have a good outcome, you can at
least guarantee that you’re giving them the best information.
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