Cancer Answers: Surgical and Radiation Treatment for Prostate Cancer, December 7, 2008

Dr. John Colberg and Dr. Richard Peschel, Surgical
and Radiation Treatment for Prostate Cancer
 December 7, 2008Welcome to Yale Cancer Center Answers with Dr. Ed Chu and
Dr. Ken Miller.  I am Bruce Barber.  Dr. Chu is Deputy
Director and Chief of Medical Oncology at Yale Cancer Center and an
internationally recognized expert on colorectal cancer.  Dr.
Miller is the Director of the Connecticut Challenge Survivorship
Program and he is also the author of "Choices in Breast Cancer
Treatment."  If you would like to join the discussion, you can
contact the doctors directly at canceranswers@yale.edu
or1-888-234-4YCC.  This evening, Ed and Ken welcome
Dr. Richard Peschel and Dr. John Colberg.  Dr. Peschel is
Professor of Therapeutic Radiology and Dr. Colberg is Associate
Professor of Surgery, both at Yale School of Medicine.Chu
 John, let's go ahead and start off by defining the population of
males who are at an increased risk for developing prostate
cancer?Colberg
Any man over the age of 50 is considered at risk for prostate
cancer.  There are some specific risk factors though. You can
look for family history, meaning one or more first-degree
relatives, father, brothers, or uncles, that had prostate cancer,
and you can also look at race.  We know that African-American
men have a higher incidence of prostate cancer and have more risk
of disease at diagnosis. And finally age, the older you become, the
greater risk you will have of getting prostate cancer.Chu
 Unfortunately, for all of us males, there is always the risk for
developing benign prostate diseases. If a male were to develop a
benign prostate disease disorder, does that place that individual
at increased risk for developing prostate cancer?Peschel
 No, it does not appear that way.  The problem is that it
develops in the same group of men, the same men who develop a
benign enlargement, or BPH, also are at risk of developing prostate
cancer, but benign disease does not confer an increased risk of
prostate cancer.Miller
 I have heard a wide variety of estimates so maybe we can clarify,
but if we live long enough, if a man lives to age 70, 80, or 90,
what is the chance that there is some cancer in the prostate, or a
cancer that will cause him trouble?Colberg
Well, those are certainly two different questions. If you look at
autopsy specimens, which we base that on, you can have prostate
cancer as young as age 30. Men who are in their 80s and 90s,
probably 70%, maybe 80%, of men will have a small focus of prostate
cancer.  It is probably not significant and there are lots of
different definitions of insignificant prostate cancers,
volume, Gleason grades and scores, etc., but yes, the older
you become the greater chance you will have prostate cancer. That
number, if you live long enough, may be up to 100%.Chu
 I am just curious, if prostate cancer were to hit someone at the
age of 30 or 35,3:01 into mp3 file 
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 would you automatically assume that cancer is going to be more
aggressive than say if it were to affect someone who is 75 or 80
years of age?Colberg
I think that the younger you are the more concerning it is, not to
say that people in their 70s do not get aggressive cancer because
they do, but certainly you have a lot more years to live when you
are 35 or 40.  Again, it is pretty uncommon.  I will see
a handful of men a year in their 40s that have prostate
cancer.  It is not a real common entity because we do
not for it.  We do not draw PSAs or blood samples routinely in
men in their 30s and 40s unless we have a specific reason.Peschel
 I think the key to answering your question is that we do have a
marker for aggressiveness and that is the Gleason score; what does
the cancer look like under the microscope?  So, independent of
age, you have a pretty good estimate of how aggressive the cancer
is going to be based on the Gleason score.Miller
 In terms of screening, what are your recommendations and your
thoughts in terms of what is good screening and at what age?Colberg
For the average American male, screening should begin at about 50
and should include a PSA, a rectal examination, and should occur
once a year.  There are subgroups of patients that should be
screened earlier, such as patients with a strong family history, or
African American males for instance, probably should be screened
earlier.Chu
 What PSA number does one need to begin to worry about? A lot of my
male friends, who go to the doctor and get the PSA, are really
obsessed with the number that comes back.  What does each of
you tend to think about in terms of the number that one needs to be
worried about?Colberg
Historically, the number has always been less than 4, and that is
probably not appropriate, especially the younger you are. 
There is what is called age reference PSA levels that one looks at,
but more importantly, it is what happens to the number over time.
For example, if you come in and your PSA is 2, certainly that is
within the normal range, but it is more important what happens over
time. If that number jumps up to 3 or 4 over a year's period of
time, even though it may be normal, that is kind of a red flag that
something probably should be investigated. It is a little bit of a
gray area for us about what actually is a normal PSA level, but
certainly under 4.  The younger you are, the lower the number
is, so if I see a man who is 45 in my office and his PSA is 3.5,
that is probably too high. But if I see an 80-year old man or a
75-year old man in my office and his PSA is 4.1, that is probably
okay.Peschel
 The other thing we are learning, particularly with the epidemic of
obesity in this5:47 into mp3 file 
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 country, is that the PSA has to be corrected for weight. Obese men
have artificially low PSAs and you have to make some adjustment for
that.Miller
 I have to say, that is a new bit of data.Peschel
 It is very interesting and discouraging to be honest with you,
because of the outbreak of obesity that is coming.Miller
 Let us get back to this issue of genetics and heredity, or the
inherited risk. Do we have any idea why, or what the mechanism is?
Is there a gene that we have identified?Peschel
 I do not think we know the cause of prostate cancer. 
Certainly, there seems to be environmental factors that are very
important.  There are some identified genes in the
African-American population for instance, but 10% of African
Americans have an identifiable genetic mutation that puts them at
risk for higher and more advanced prostate cancer.  In our
department, we are studying a nick in the DNA that can be
identified and associated with prostate cancer and higher failure
rates. We are looking, but we have not found a full answer yet.Colberg
And I think most prostate cancers are sporadic just like colon
cancer, breast cancer, or kidney cancer.  There is a genetic
component in a small portion, but most of them are sporadic, they
have no family history or family history that is significant.Miller
 What are some of the typical symptoms that an individual might
experience?Colberg
Most patients do not have any symptoms.  The main reason they
come to the office and have been biopsied or diagnosed with the
prostate cancer, is because they have had an elevated PSA level.
Occasionally, they will have some BPH symptoms described earlier,
slowing of the stream and getting up at night, but those are not
specific for prostate cancer.  It is pretty uncommon
now-a-days to see people who come in with symptoms of metastatic
disease, or advanced disease like bone pain, pelvic pain or urinary
retention, things like that, which you used to see 20 or 30 or 40
years ago.  You do not see that very often.  Most men
have no symptoms with their low grade or localized prostate cancer,
early prostate cancer.Peschel
 I agree with that.  Most men have symptoms because they have
benign prostatic hypertrophy, and that is what brings them to the
urologist.  Almost nobody has a symptom anymore from prostate
cancer because of PSA screening.Miller
 When we talk about cancer in general, people are scared. I think
this is one of8:23 into mp3 file 
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 the reasons why men and women do not do the tests that perhaps
they should have done, but if you are suspicious as a clinician
that someone may have prostate cancer, how do you make the
diagnosis? Is that a big operation? Is that something for people to
fear and avoid?Colberg
People will usually come in with an elevated PSA level, or during
an examination with your finger, when you feel the man's prostate
if there is a lump or a nodule, or firmness, and the way we make
the diagnosis is with a biopsy done in the office.  They are
called transrectal, meaning we put an ultrasound probe in the
rectum and we take the biopsies of the rectal wall under local
anesthesia, and it is an office procedure.  It is very well
tolerated.  It is not painless, it is uncomfortable, but it is
well tolerated and usually we will have the answer in 48 to 72
hours when the pathologist looks at the slides.Chu
 Then once the diagnosis of prostate cancer is made, what goes into
the decision making process as to what treatments should be
recommended to that individual?Peschel
 There is a wide spectrum of choices that patients face.  You
look at their general health, commorbidities, their age, their
Gleason scores are particularly important, the PSA which is the
blood test, and then their physical exam. The choices that you can
lay before them go all the way from careful observation without
treatment, surgery and radiation therapy, so it's a wide choice,
but it is all based on general health, PSA, Gleason score, and
age.Colberg
There is no one cookbook answer for every patient.  I try to
emphasize that with my patients, that a decision that is right for
them, may not may be the same for someone else. Someone may be a
very good candidate for surgery, and another person may be a better
candidate for radiation therapy. There is no right answer, there
may be better answers, but there is no absolute right answer for
each patient.Chu
 We are going to have an opportunity to get in depth about the
treatments that both of you have to offer to patients, but let me
ask about a different group, who are the men that you would
consider watchful waiting for?Peschel
 A typical patient that we would think about watchful waiting for
would be an elderly patient, perhaps in their late 70s, a patient
with severe medical problems, heart disease, lung disease, kidney
disease, and a life expectancy less than 10 years, they would be
good observation patients; also patients with low Gleason scores.
The scoring system goes from 2 to 10.  If you see a patient
with a Gleason of 5 or 6, we usually would discuss observation with
that particular patient.  It is like you know them when you
see them, and observation is a perfectly good option for many of
the patients that we see.11:17 into mp3 file 
http://www.yalecancercenter.org/podcast/Answers_Dec-07-08.mp3Colberg
There is even growing evidence and people are trying to define
someone who has maybe a low volume, very localized disease, and
that is the hard part. Even younger men could be considered for
that protocol, but it is a very intense protocol meaning they
follow up with you four times a year with PSA levels, rectal
examinations, they get repeat biopsies at a year or 18 months to
see and make sure that you actually do have low volume disease. We
are not saying they are never going to be treated, but there may be
a delay of treatment so that 6 months or a year down the road, they
may be treated as opposed to immediately, but it is a very, very
tricky dilemma to propose.Peschel
 There is some risk involved, the needle biopsy, which is what you
are trying to make a decision on, is about 10% to 15% inaccurate.
 There could be a higher grade tumor hiding somewhere that the
biopsy did not see.  Secondly, the tumor can transform itself
from a very low-grade to a higher grade after two, three, or four
years.  Many patients need to have repeat biopsies to keep
track of that.Miller
 Is there ever a role for imaging of the local prostate disease,
such as with CAT scans or MRIs? Typically you do not use that as
part of the evaluation process.Colberg
If you look at men who have PSAs under 10 and Gleason scores of
less than 8, the yield of bone scans and CAT scans and MRIs are
pretty low.  The way I use, for example the rectal MRIs or
MRIs, is to look at the local disease.  If someone is on the
border, maybe he would be a good surgical candidate but you are not
certain, maybe there is disease outside the prostate gland, maybe
their PSA is 15 and they may have Gleason 8, sometimes an MRI will
make the difference in suggesting he have surgery versus having
radiation therapy.Peschel
 I think the role of other diagnostic tests is less important
because the PSA is such a good screening tool. They are picking
patients up who have very early disease, microscopic disease, and
generally a CT scan or MRI scanner all that is useful for the
average patients.  It is very important for the patient
between choosing surgery or radiation, but not so important in
terms of staging.Colberg
I think that in the next 5 to 10 years we are going to come up with
a better imaging spectroscopy, ways to identify small or
microscopic disease within the gland that you could do some focal
therapy with, or find that person who has really low volume disease
that you want to follow, but we are not quite there yet.Miller
 In breast cancer, we went from radical mastectomy to modified
radical, and now to lumpectomy, and even the idea of very localized
radiation to a part of the breast, do you see that happening in
prostate cancer?14:16 into mp3 file 
http://www.yalecancercenter.org/podcast/Answers_Dec-07-08.mp3Colberg
 I think it will happen.  It is just that we do not have the
imaging technology or the capabilities yet, plus prostate cancer
tends to be a multifocal disease so that even if you have biopsies
on one side, or one particular area, and when we take the prostate
out, the disease will be in several areas of the prostate, so again
it is a very tricky proposition but that is where we are
headed.Peschel
 I agree with that.  When I started treating prostate cancers
30 years ago, the vast majority of patients had disease outside the
prostate at diagnosis; it had already spread before
treatment.  Now, probably 90% or more of the patients have the
disease confined to the prostate. The exception is huge stage
migration and I think the next step I agree with John, MRI
spectroscopy can now plot the three-dimensional distribution of the
tumor inside the prostate and it should be possible to use even
more focal treatment rather than just treating the entire
prostate.Miller
 That is very exciting.  We are going to take a break now for
a medical minute. We will be back with Dr. Richard Peschel and Dr.
John Colberg from Yale Cancer Center talking about prostate
cancer.Miller
 Welcome back to Yale Cancer Center Answers.  This is Dr. Ken
Miller and I am joined by my co-host Dr. Ed Chu and our guests Dr.
John Colberg and Dr. Richard Peschel, who are experts in the
treatment of prostate cancer. Let me ask you, for patients
diagnosed with prostate cancer, who is on the multidisciplinary
team and how do you use that team approach?Peschel
 We work very well together as a team, and John and I have
developed the philosophy over time and we are very, very
comfortable in terms of deciding who gets surgery and who gets
radiation. Kevin Kelly, in medical oncology, is also part of that
team.  We have a conference that meets twice a month to16:52 into mp3 file 
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 discuss difficult patients.  There is a large, wide spectrum
of expertise that is involved in helping patients make a
decision.Colberg
Often times these patients, even though they may have surgery or
they may have radiation therapy, often times they may need other
things. They may need radiation therapy after their surgery, they
may need hormonal therapy, so it is more of a multidisciplinary
approach to all these cancers, not only prostate but all of the GU
cancers.Chu
 As you were saying earlier John, the decision to undergo a certain
treatment is very individualized. I know all of us have friends and
colleagues who have had early stage prostate cancer and have gone
through the anxiety of trying to determine whether or not they
should undergo surgery versus radiation therapy. Maybe you can take
us through the pros and cons, advantages and disadvantages, from
your advantage point?  John, we can start off with you.Colberg
Well as you know I do the surgery, but I am fairly open about it
and I try to give the patients all the options. In general, we
operate on younger more healthy patients, now that does not mean we
do not operate on a 70-year-old man, we do, but in general terms,
that is the first thing you look at, then you look at the stage of
disease.  You want to operate on localized prostate cancer,
people who do not have disease outside the prostate, and that is
based on patient examination, the patient's PSA level and
pathology, the Gleason score, which you have talked about several
times, and then ultimately my role is to give the patient as much
information as I can. A lot of men come in with an idea of what
they want to have done and they are just confirming or determining
if it's the person they want to take care of them, but often times
we will send patients back and forth between Dr. Peschel and
myself. I'll have a patient I think is a surgical person, but just
to circle the wagons and make sure he is comfortable with
everything I'll send him to Dr. Peschel and he will talk with him
about radiation therapy.Peschel
 Obviously a big concern that either is, or is not discussed, but
clearly is in the forefront of a lot of males' minds, is this is
issue of sexual function after surgery and the high risk of
impotence.Colberg
There are two big down sides of surgery, and for radiation one is
the same, and that is a loss of sexual function or erectile
dysfunction and incontinence, the inability to control your urine
after the operation. Those are very, very concerning issues, not
that they can't be handled if you develop those after surgery, but
certainly that is a big concern of all the patients, and if you
look at surgery, for someone who does a safe number of radical
prostatectomies a year, you are talking in the sense of
incontinence of anywhere from 3% to 5%.  Erectile dysfunction
or sexual dysfunction is based on two things, the age of the19:57 into mp3 file 
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 patient and what their status is before the operation. If you have
a 50-year-old man who has good erections before the operation, your
success rate with surgery if you do nerve sparing is probably
somewhere between 70% to 80%.  If you are 70 years old and you
have fair erections, it is probably more like 10% or 20%.Miller
 I want to ask the same thing with radiation, because again these
are the issues that men are going to be asking about. If you treat
a man with radiation and he has the same issue as that 50-year-old
and 70-year-old man, what are the risks?Peschel
 The question with radiation therapy is that most of our patients
who have more advanced disease, higher grade, will also receive
hormone therapy, and the combination of hormone therapy and
radiation therapy produces more erectile dysfunction than that of
just radiation therapy alone.  For those that just get
radiation, erectile dysfunction is about 20% to 30%, very similar
to surgery, but we need to use hormones in many patients and the
impotence rate climbs to about 50%.Chu
 It is interesting because I think the general misconception is
that with radiation therapy there is no risk for developing
erectile dysfunction.Peschel
 Yeah, there are a couple of components to that.  One of them
I mentioned, the use of hormone therapy definitely adds to erectile
dysfunction, and secondly, our age group is older; our average
patient is about 70 to 78 years old. Surgical patients are said to
be younger, so they have fewer age factors in terms of whether
they'll be potent or not.Chu
 And with surgery people will not immediately be potent after the
operation, it may take six months to 12 months to actually recover
their sexual function.Peschel
 To be honest with you, the data documenting potency sparing is
very poor.  It is very soft data.  There are not really
any good studies, so when we talk about these numbers, they are
very soft numbers.Chu
 Have the complications secondary to radiation therapy improved now
that you are developing more sophisticated focused approaches to
deliver the radiation therapy to patients?Colberg
Yes, the complication rights have fallen dramatically.  This
intensity-modulated radiation therapy, which we have used at Yale
for over 10 years, has produced complication rates that are the
lowest we have ever seen.  All other types of radiation
therapy that we used in the past for prostate cancer produced 6% to
15% complications that affected quality of life.  With IMRT,
based on 800 patients that we have treated, it is down to less than
1%, we've just never 22:43 into mp3 file 
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 seen anything like it. Now we are moving into what is called
image-guided intensity-modulated radiation therapy, which should
allow us to escalate the dose more but maintain these very low
complication risks.Miller
 Since we are talking about radiation, can you tell us a little
about seed implants, what are they and who should receive that
treatment?Colberg
We used to do a lot of seed implants; I have done 500 myself. 
It is the placement of little tiny radioactive seeds into the
prostate in a set distribution to produce a minimum dose to the
outside of the prostate.  There are two different isotopes
that are used; one is iodine-125 and the other is
palladium-103.  We have tended to use palladium here at Yale
because of the shorter half-life.  In an amazing way, we have
set aside prostate implant at Yale because our intensity-modulated
radiation therapy results are so good, the complication rate is
1/10th that of implant, and the cure rates look better than with
implants, so we have tended to emphasize in our patient population
intensity-modulated radiation therapy.Peschel
 John, as we have been talking about the advances in radiation
therapy, there also have been some pretty significant advances in
surgical techniques.Colberg
The most recent advance is the idea of minimally invasive
prostatectomy using a system called the da Vinci System, which is a
robotic-type system.  It has been around since early
2001-2002.  In that time, there have been around 400 prostates
done that way.  In the United States now, probably 50% of all
prostatectomies are done robotically.  In the next five years,
80% or 90% will be done robotically. What the system is, is it
operates through small little punctures in the lower abdomen, in
fact we make about six little holes in the abdomen, and through
these little holes we have a camera and working ports where you are
actually able to operate this robot remotely from across the room
and do the same operation.  The advantages are several; one,
less blood loss, less time in the hospital, less pain, and less
time with the Foley catheter.  As far as the important things
of prostatectomy, such as cancer control, it seems to be equivalent
to open operation. Potency may be a little bit better and the
return of erectile erections may be back sooner with the robotic
prostatectomy. And with incontinence, it may be about the same at a
year, but may also be controlled a little bit sooner. We have had
the machine, the robotic system, at Yale for about two plus years,
and I would say 95% of our patients have robotic
prostatectomies.  There is always a rare instance where you
need to still do an open procedure, and there is always a risk when
you do robotic prostatectomies that it may need to be converted to
an open operation because they can't be done robotically, but it is
very exciting.25:49 into mp3 file 
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 I want to ask you, John, because you have done both kinds of
procedures, for you as a surgeon, what is it like on the other side
of the room?Colberg
Certainly there is a learning curve to the procedure.  It is
not a huge learning curve for someone who has done a lot of open
operations and is very adept at laparoscopic skills, but it is a
different operation, it has much better visualization and you see
things that you probably did not see before. The way you dissect
things is more exact, dissect the nerves and preserve the sphincter
for the urethra, so I think that it is a very good operation and is
definitely here to stay.Chu
 Is this robotic surgery just for prostate cancer, or potentially
could it be applied for surgical resection of other tumors?Colberg
Certainly they use it for a lot of different tumors.  They can
use it for a pediatric population for pyeloplasties, obstructions
in the kidney, people have done it for partial nephrectomies,
radical nephrectomies, general surgery has used it for distal
pancreatectomies, colon resections, thoracic uses it,
cardiovascular uses it for mitral valve repairs, urology will use
it eventually and people are already using it to remove bladders
for radical cysto-prostatectomies. It is just beginning to take off
as far as what it can be used for.Peschel
 The good news about this procedure is that John has appropriately
advanced the age where patients can have surgery. The average age
of patients having surgery used to be 58, and I think John pushes
that up to 68 or 69, so it gives older patients the opportunity to
think about the surgical option.Miller
 A man comes to you who is 50 years old, let us say, with a PSA
that is 3 or 4 and an intermediate Gleason's grade. I am trying to
paint a high risk, and not a low risk patient, and he says to you,
"What is better, should I have radiation or should I have
surgery?"  How do you answer that?Colberg
We have developed a philosophy at Yale that the younger patients
should be offered surgery.  The reason for that is that an
average 50 year old will live 25 years easily, and you need to look
at the long-term data and the long-term data for surgery is more
robust and it is better defined.  So we really emphasize
surgery in the very young patients.Chu
 Is there ever any role after surgery for additional radiation
therapy plus or minus hormonal therapy?Colberg
That is a great question and that comes up for a lot of
patients.  With PSA it tempers it a bit because if you have a
prostatectomy and your PSA becomes undetectable or zero, there is
no evidence of disease.  What happens to the man28:54 into mp3 file 
http://www.yalecancercenter.org/podcast/Answers_Dec-07-08.mp3whose PSA starts to go up after surgery? That gets to be a very
difficult dilemma because there are certain parameters you are
going to look at, when did the PSA go up, what did the original
pathology show? Maybe Dick can describe what our philosophies are
on who we radiate.Peschel
 There are two programs, one is called adjuvant radiation therapy,
if you see poor pathologic findings at surgery you immediately
treat the patient with post-op radiation therapy. The other is
called salvage radiation therapy where you wait for the patient's
PSA to become detectable and then treat with post-op radiation
therapy; the two are very different approaches.Chu
 You have been listening to Yale Cancer Center Answers and we would
like to thank our guest experts, Dr. John Colberg and Dr. Richard
Peschel for joining us. We look forward to having you back on a
future show.  Until next time, this is Dr. Ed Chu from the
Yale Cancer Center wishing you a safe and healthy week.If you have any questions for the doctors or would like to
share your comments, go to www.yalecancercenter.org
where you can also subscribe to our podcast and find written
transcripts of past programs.  Next week, Dr. Peter Marks
joins us to discuss leukemia.  I am Bruce Barber, and you are
listening to the WNPR Health Forum from Connecticut Public
Radio.