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Program Supplement
INTERVIEW WITH DR MARK SOLOWAY
DR NEIL LOVE: Later
on in the program, Dr William See will review the emerging data
on the randomized trials referred to by Dr Schellhammer on the early
use of bicalutamide in men at increased risks for progression. One
of the major goals of the patient perspective research project Dr
Mark Soloway and I are implementing is to collect data on the perspectives
of patients on the risks and benefits of early endocrine therapy.
Dr Schellhammer noted how different his perceptions have been as
a patient compared to his experience as a physician. Prostate Cancer
Update will also include case presentations of patients cared for
by the investigators being interviewed, and to begin, Dr Soloway
presents a patient from his Challenging Cases in Urology meeting.
DR MARK SOLOWAY: This is a forty-one-year-old
professional who is going to get his cholesterol checked and he
said let's throw in a PSA. PSA was 15. Much to his surprise it was
repeated and it was also 15 on repeat. He had no evidence of urinary
tract infection, nothing that suggests prostatitis, so he underwent
ultrasound with guided biopsies of the prostate. Three of the biopsies,
two from the right, one from the left out of a total of six indicated
a Gleason score of 3+3 or 6 prostate cancer. The digital rectal
examination was entirely unremarkable. And clearly, even most radiation
oncologists would suggest prostatectomy to someone in this age group.
The key issue is, given the fact that his PSA is high, that he has
three of six biopsies positive on both sides, and even though the
prostate feels totally normal, should one do a nerve-sparing procedure?
I think that is the major issue. In my view, the dilemma one has
with a patient is, you are there to eradicate his cancer. That should
be issue number one. One thought would be don't compromise that.
The other would be, if you can't leave the fascia on the prostate
intact and preserve the nerves and accomplish both things, the likelihood
that you're going to make a difference with that technical alteration
of coming widely or not is very small. That that's going to be the
only thing that doesn't cure the patient.
Since it is likely if he fails, it's going to be with systemic
as opposed to local disease, and since erections are very important
in terms of quality of life. Erectile function is very important
for men; no question and we've learned that. And here's a young
gentleman. Go ahead with the nerve sparing because if you bet wrong
and if he has only local recurrence then radiation therapy afterwards
is a reasonable alternative. So that would be my argument. But this
would be the dilemma. Anyway I did perform a bilateral nerve-sparing
prostatectomy, and fortunately he remains NED. His PSA has been
zero, this is now about 6 years later. His PSA is undetectable;
he is potent and fully continent.
DR LOVE: You raised
the question of compromising local tumor control or cure. Do you
think that nerve-sparing surgery does that?
DR SOLOWAY: In my opinion it
does probably in a rare patient, but given large numbers of patients,
I think it makes no difference.
DR LOVE: Did you
present that to him in that way?
DR SOLOWAY: Yes.
DR LOVE: I guess
in a sense he was willing to take a chance.
DR SOLOWAY: I think the chance is very small,
and therefore the benefit is such a large one, because if you have
neither or certainly one of the neurovascular bundles totally removed
the likelihood of erectile function is so much diminished. Then
you are relying on other means of erectile function, which are not
terrible, but if you can have fairly normal erections that is clearly
a major advantage.
DR LOVE: Now you've
presented this case to some of your Challenging Cases conferences,
what did the respondents say?
DR SOLOWAY: The majority would do nerve sparing,
remember that this is an interesting issue. There are many urologists
who do not do nerve sparing very often. They feel the people who
do it compromise the cancer surgery. I think the majority of urologists
in academic centers, and I am just guessing now, would do a nerve
sparing even with this fellow's initial PSA of 15.
DR LOVE: What percent
of your patients are getting nerve-sparing surgery?
DR SOLOWAY: At this time, a high percent because
most of the patients have good prognostic factors, clinical stage
T1C, Gleason scores 7 or less, non- palpable disease. 70 or 80 percent
will fit into that category.
DR LOVE: You've published
a paper recently looking at no sparing surgery in terms of recurrence,
can you talk a little bit about that?
DR SOLOWAY: We have a paper on press in the Journal
of Clinical Oncology. We compared in a retrospective fashion the
patients who did or did not have bilateral or unilateral nerve sparing
procedure. So we looked at the unilateral-bilateral together as
one group and no nerve sparing. If you look at PSA recurrence absolutely
the lines are superimposable over time.
DR LOVE: So the question
you were addressing is, by doing this surgical procedure are you
potentially compromising the chance of cure, and what you found
was you are not?
DR SOLOWAY: In looking at large groups of patients
as opposed to an individual patient, which of course is difficult,
I do not think there is difference. Do I think there might be some
small group of patients, in which you'll have a local recurrence
because you did a nerve sparing? Yes. But I think I would agree
with Dr Walsh and some of the other thought leaders, who have looked
at this, and that percentage is probably under 10 percent if that
high.
DR LOVE: What percent
of your men who have no sparing surgery retain normal erectile function?
DR SOLOWAY: I must say, I have not done a very
rigorous analysis of that recently, and that is something one should
do. I would say it is very age dependent and it's dependent on two
other factors. Pre-operative potency of course is critical and time
is very important. It may take one or two years of follow up to
be able to have an adequate answer to that question, and were both
nerves, as opposed to one nerve involved. So a man who is 50-55
who is given one to two years and may or may not use Viagra, so
allow the inclusion of Viagra, probably 70 percent of them have
very reasonable erectile function.
DR LOVE: This audio
program is patterned after a similar series for medical oncologists
on breast cancer that we have produced since 1988. During this time,
we learned that a convenient method to supplement research leader
audio interviews was to use a Web site that provided the full transcript
of the audio program with related web links to journal articles,
abstracts, and protocols. We have incorporated that model into Prostate
Cancer Update, and you can find the transcripts of this program
and links to key journal articles on ProstateCancerUpdate.net.
Another major and very controversial issue in prostate cancer management
- and a key focus for our patient preferences project - has been
the timing of androgen deprivation therapy. A major review article
by Walsh et al, last summer in the Journal of Urology discussed
this topic, and is cited in the booklet accompanying this audio
program. A number of Dr Soloway's challenging cases involved decisions
in this regard, including the next case he presented of a sixty-six-year-old,
very healthy man he recently evaluated.
DR SOLOWAY: He came to see me because of a decrease
in his ejaculate volume. That was his chief complaint. He had mild
lower urinary tract symptoms of nocturia and hesitancy. PSA obtained
in my office was 5.9. Importantly, he has a past medical history
of ulcerative colitis, which currently is asymptomatic but has been
treated with medication. A digital rectal examination, as part of
his initial evaluation, indicated a moderately enlarge prostate
of approximately 35 grams and there was asymmetry with the right
side being firmer than the left. I informed him of this information
and proceeded with a transrectal ultrasound indicating a 37 gram
prostate. I also proceeded with multiple biopsies, eight in total
using a periprostatic nerve block, and all eight of the biopsies
were positive for Gleason 3+4 or 7. A bone scan and CAT scan were
performed and both did not indicate evidence of obvious metastatic
disease.
So, once again we have a gentleman that is really not likely to
be cured by local treatment. One might clearly offer this fellow,
first of all possibility of how about a node dissection. Let's first
determine what the chance is, and they are high, of having positive
lymph nodes, and then making a decision. Probably many years ago
a laparoscopic pelvic lymph node dissection would have been a major
consideration. Some people might still do that. Some might do a
mini lap, particularly if one is going to use radiation therapy
as a primary local treatment, since this might alter the decision
if his tumor was involving the regional lymph nodes. One may, therefore
elect not to give him as a choice prostatectomy or radiation therapy.
When I asked a group of urologists in this particular case what
they would do, three-quarters of them indicated that they would
remove his prostate, lymph node dissection would be part of that
and this might be preceded with hormone therapy. Some of them would
do that. So one couldn't really argue with any form of local treatment,
but it would be reasonable, even though he has clearly adverse prognostic
factors to try and cure this gentleman.
Well, I took him to the operating room and found that he had palpable
enlarged lymph nodes, on the right side in particular. Sent this
for frozen section and it indicated adenocarcinoma of the prostate,
particularly in one large lymph node. The other lymph nodes were
negative, both by permanent and subsequently in frozen sections.
Now the question interoperatively is, do you proceed with a prostatectomy?
That's a big decision. Some people would say, let's stop give this
man hormone therapy alone. A few would say, stop and give him radiation
therapy in combination with radiation therapy. And many, probably
the majority of urologists, and this may be one area where it's
separated between university-based and community-based urologists,
because I've asked this question many times and there is a pretty
pronounced disparity. I proceeded with a radical prostatectomy and
I think the key for me there, in making that decision is you must
be able to do the operation with minimal morbidity. You would not
want to add the side effect of incontinence to a patient you are
not likely to cure or you are not going to cure, frankly.
But on the other hand, you can minimize any local problems if and
when he relapses by removing the prostate. But again, you must provide
him a situation where you don't add to the morbidity of the already
performed laparotomy, or the performed lymph node dissection.
The final pathology in this gentleman indicated a Gleason 9 prostate
cancer, he had bilateral seminal vesicle involvement and the final
pathology indicated that none of the nodes on the left were positive,
but four of nine nodes on the right, when I extended the node dissection,
were positive.
Now the question is what does one do now? He's had positive lymph
nodes, you discussed the pathology, and some still might say let's
monitor the PSA, let's give him a window without the outside effects
of hormone therapy. The other alternative would be let's initiate
androgen deprivation. I think the majority of urologists would do
that and in this case, I strongly urge that he have it based a little
bit on this Eastern Cooperative Group study. But I think I would
have done it even without the results of that study, and he was
started on LHRH and an anti androgen. Actually I have suggested
that he undergo subsequently at the time of his choosing, a bilateral
orchiectomy, since I don't think this would be a good candidate
patient for intermittent therapy.
DR LOVE: What did
you tell him his chance of progression is in the long run?
DR SOLOWAY: Well, I didn't tell him because it's
a 100 percent. Sooner or later if he lives long enough, he will
have progression and will need other treatment besides hormone therapy.
DR LOVE: It's interesting,
did he not ask you?
DR SOLOWAY: Not that I recall.
DR LOVE: How is he
doing now?
DR SOLOWAY: He's doing very well. He has the
side effects of the androgen deprivation, which he minimizes. He's
fully continent, obviously he has severely diminished libido and
erectile function, those are his main side effects. Some hot flushes.
DR LOVE: Do you think
there are some urologists who would just manage him without therapy
and just follow him?
DR SOLOWAY: Probably, I would say it is the minority,
in my view.
DR LOVE: What's his
PSA been doing?
DR SOLOWAY: It's undetectable.
DR LOVE: Anything
else about this case that you think is worth talking about?
DR SOLOWAY: No, other then, it would have been
not unreasonable to, once you operated and found the positive lymph
nodes to stop the surgery at that point and proceed with just hormone
therapy. It'd be tough to prove that adding the prostatectomy is
helpful. Now, the Mayo Clinic group has advocated for many years,
that there's an advantage to removing the prostate. They have looked
at their patients who had hormone therapy alone and the patients
who had hormone therapy plus removal of the prostate. They've found
in diploid tumors, now we don't know what his ploidy is, that there's
a very significant advantage in terms of progression-free, and I
believe even, overall survival if they remove the prostate. This
suggests that the presence of the prostate with the tumor burden
may cause additional metastases.
DR LOVE: What about
from the point of view of local morbidity?
DR SOLOWAY: It's not very well quantified. Urologists
have not been very good in taking people with hormone therapy who
have a prostate still present, of course, and determining what is
the chance of local problems. It's not minimal. Bleeding, urethral
obstruction - as individuals progress, if I had to guess at a number
it would be 10-15percent of such patients will have such a problem.
DR LOVE: One of the
great challenges in medicine is to determine when clinical research
findings are appropriate to bring into patient care. Dr Hayes points
out the downside of waiting too long, by citing the adjuvant tamoxifen
data, and the potential adverse consequences of adapting therapies
too early with the high dose chemotherapy issue. The prostate cancer
patient preferences study, which will be discussed more in the next
issue of Prostate Cancer Update brings the patient perspective into
the complex decision making process of management of early stage
disease. It raises the issue of more actively involving men with
the disease in the decision-making process.
To conclude our program, we present another series on challenging
cases, beginning with a 57-year-old patient of Dr Soloway who had
been treated for several years for presumed prostatitis.
DR SOLOWAY: During the two or three year period
where he had these recurring episodes diagnosed as prostatitis with
perineal discomfort, and voiding problems, he had three sets of
prostate biopsies by the transrectal route, all of which were negative.
His PSA when I saw him had increased from 0.6 to 1.3 over approximately
a year. Because of his persistent voiding complaints, the urologist
that was taking care of him performed a transurethral section of
the prostate. Surprisingly, that is both to the patient and certainly
to the urologist, found a Gleason score of 9 prostate cancer. Scans
were performed that were negative. When I saw him, I did a digital
rectal examination and I thought he had palpable disease that may
have even extended beyond the capsule of the prostate. But since
he had a previous TUR that's very difficult to determine with any
accuracy. Other scans were negative for obvious metastatic disease.
So this is clearly again a gentleman with adverse prognostic factors
and the question comes up, what should be the role of surgery-radiation
therapy, and maybe is this a candidate for initial chemotherapy?
He's young, very healthy, and has a low PSA suggesting his cancer
is not expressing PSA. We talked to him about an approach which
is experimental, investigational, and that is using chemotherapy
in conjunction with hormone therapy for several months prior to
making then another decision which would be in the form of more
definitive local treatment. Using the term definitive, in other
words, what form of additional local treatment.
The patient understood this and agreed to proceed with this investigational
concept and received a combination of estramustine phosphate, VP16,
Taxol and an LHRH analog. He had five months of this therapy, and
in October 1998, I performed a radical prostatectomy, which was
quite uneventful. The lymph nodes were negative; the Gleason score
was 9. It was a high-volume tumor, 65percent of his prostate contained
tumor. The surgical margins were negative but the tumor did extend
into both seminal vesicles. The patient has continued the androgen
deprivation with an LHRH analog.
As of recently, within two months, when I saw him, he's fully continent,
PSA is undetectable, and one of the issues, which we still have
not decided upon, is, should we discontinue the androgen deprivation?
At this point he is continuing it, and I must say I don't know what
the right answer is. At some point, I'm sure we will discontinue
it, and see what will happen to him if he can be off androgen deprivation
for a period of time. But it is somewhat risky to do so.
DR LOVE: How do you
think the initial management, of course he was on an experimental
study, if he hadn't been on an experimental study how would you
have treated him?
DR SOLOWAY: Well, the choices would be either
androgen deprivation followed by prostatectomy or prostatectomy
alone.
DR LOVE: What would
you have done? What would you do today?
DR SOLOWAY: Given his age, I would have removed
the prostate, determined the pathology and lymph node status. Then
if he has local recurrence alone he has a possibility of now receiving
radiation therapy.
DR LOVE: Dr Soloway's
final challenging case concerns management of the elderly patient
with prostate cancer particularly the dilemma regarding local therapy.
DR SOLOWAY: This gentleman is 75 years old and
in excellent health. He plays tennis three times a week and his
PSA has been checked quite regularly. Over the last three years
it has gone from 4.9 to 6.7. He underwent an ultrasound with guided
biopsies of the prostate and a small-focus, Gleason 6 was noted.
I examined him, and I thought I could feel some asymmetry so I called
him a clinical T2. His prostate was 65 grams, so the PSA density
is only about 0.1. He was totally asymptomatic.
Lots of choices here and I think there are probably six or seven
very good choices that one could have for such a patient. Interstitial
therapy, a lot of people might do that for treatment. External beam
very reasonable and some radiation oncologists prefer both, to get
very high dose radiation therapy. Intermittent androgen deprivation
is not unreasonable particularly if you are going to use interstitial,
some would want to shrink the prostate with androgen deprivation
followed by radiation therapy. Some people might just observe this
gentleman, and say why are you treating him? He is 75 and he's got
a small focus of cancer, this is excellent for observation. At 75,
I think very few would want to remove his prostate.
Actually this patient, after hearing all of that, chose to have
the combination of external beam radiation therapy and interstitial
therapy. So in 1997 the androgen deprivation with an LHRH analog
and an anti-androgen was initiated. He took this for nine months
and his prostate had decreased in size. He was quite asymptomatic
except for some side effects from the hormone therapy, which are
not unusual. Then he said - I am doing so well, I'll just continue
with the hormone therapy. He did that for another three months and
his PSA was then 0.1. So at that point one might raise the question,
well let's stop the hormone therapy, he only had a small focus of
cancer initially. Why not do that?
This was discussed extensively with this gentleman and the hormone
therapy was in fact stopped. So he took it for one year. One could
have rebiopsied him to help determine that, but we elected not to
do that. In December of 2001, just recently I saw him, I've been
following him every six months. He is currently seventy-nine, he's
very fit, his PSA is 4.5, his prostate feels normal and he is totally
asymptomatic. I can't look into the future what will happen but
I think this fellow has had very reasonable treatment.
DR LOVE: How do you
think he would have been treated in the spectrum of treatment in
the community?
DR SOLOWAY: My guess is there is a broad range.
I think many people certainly would have proceeded with radiation
therapy, and the patient was prepared for that. That was the initial
choice. I think the patient reevaluated after he saw what happened
to his PSA and he was doing pretty well with the hormones, so he
said let's just continue this, why subject myself to any potential
side effects.
DR LOVE: What would
you have done if he'd been 85?
DR SOLOWAY: Probably nothing, observation.
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