The Treatment of Localized Disease
Introduction |
Warning to patients |
"Watchful waiting" |
Pelvic lymphadenectomy |
Radical surgery |
External beam radiation therapy |
Brachytherapy |
Cryosurgery |
Neoadjuvant and adjuvant hormonal
therapy |
Post-surgical radiation therapy
Introduction
Localized prostate cancer is cancer confined to the prostate, but can
include situations in which the cancer invades into -- but not through
-- the prostate capsule, which defines the border of the prostate. As
discussed in the section on clinical
staging, such cancers are known as stage T1 or stage T2. Localized
prostate cancer is potentially curable in a very high proportion
of patients, which means that, at least in theory, all of the prostate
cancer cells can be removed or killed, with the result that the patient
does not go on to have recurrent prostate cancer.
The key problems with the management of localized prostate cancer are
twofold. First, prostate cancer which appears to be localized according
to all of the tests carried out prior to surgery may, in fact, not be
localized at all (see the section on misstaging). Second, even though the cancer
is confined to the prostate, it may not be possible to either remove or
otherwise destroy all of the cancer cells because of surgical or other
treatment problems.
There are three basic types of management currently considered to be
standard options for the care of patients with localized prostate
cancer: (a) so-called "watchful waiting," (b) radical surgery to
remove the prostate, and (c) various forms of external beam radiotherapy
to kill the prostate cancer cells. In addition there is a range of
experimental options currently under investigation, including
cryosurgery, brachytherapy (radioactive seed implantation), and the use
of "adjuvant" or "neoadjuvant" hormone therapies in combination with
surgery or radiation. In this section, we will discuss all of these
subjects in some detail.
Warning to patients
Patients are warned that ALL treatments for prostate cancer are
controversial to a greater or lesser degree. There are few if any areas
of complete agreement within the medical community about the appropriate
treatment of any particular stage of prostate cancer. For this reason,
patients are strongly advised to seek as much advice and knowledge as
they can reasonably manage to obtain prior to making decisions about
their treatment. In particular, patients should be aware that all
treatments currently available and carried out with the intent to cure
localized prostate cancer have been associated with high probabilities
of failure and/or significant adverse effects on quality of life.
"Watchful waiting"
Are there people who don't need treatment?
Physicians have always known that it is probably better not to
attempt to treat some patients with localized prostate cancer.
These patients just wouldn't be able to deal with the rigors of the
types of treatment available. However, there has been much controversy
about this topic in the recent past -- largely related to exactly which
patients are not appropriate for definitive treatment with radical
surgery or radiation therapy. This is just one of the many
controversies about the proper management of prostate cancer, and it
exemplifies why it is so important that patients try to understand as
much as they can about how their disease can be managed and the
potential benefits and risks attached to each type of management.
Case example 1: Chuck P. is 82 years old and long retired.
He has been having regular medical care for the past 16 years. He has
adult onset diabetes, high blood pressure, and considerable difficulty
with his breathing. Despite everyone's advice, he is still smoking 10
or more cigarettes a day. Many days he is unable to do much more than
sit in the chair in the living room while his wife, Alice, runs the
house with some help from their daughter and grandchildren, at least one
of whom tries to come by every day. This year, during Chuck's most
recent visit to his doctor, the doctor thought he could feel a very
slight abnormality in Chuck's prostate when he carried out a DRE. Chuck
asked the doctor to explain what this could mean. The doctor told Chuck
that prostate cancer was one of several possibilities and said he wanted
Chuck to have a PSA test. Chuck had never had this test before. When
the result came back, the doctor told Chuck his PSA was 12.8 ng/ml, and
they needed to talk about what to do.
Now Chuck is almost certainly a prime candidate for watchful waiting.
He is not a young man, and he already has significant health problems.
The chances are that his prostate cancer is localized, and it could be
years before it progresses to the point at which Chuck develops clinical
symptoms of prostate cancer. If he has prostate cancer confirmed by a
biopsy, then he has to consider whether the likely side effects of
surgery or some other form of therapy will be worse for his quality of
life than not having any therapy at all until his disease progresses.
In truth, Chuck may not live long enough to ever develop symptoms of
prostate cancer. Should he really put himself through the risks of
surgery or another form of therapy? Chuck's doctor might well recommend
that, rather than consider treatment, he would prefer to monitor Chuck's
prostate on a regular basis (say every 6 months) with a DRE and PSA
tests. If there is no significant change in Chuck's PSA or his DRE,
then there may be no need to treat Chuck ever.
Of course, there are also other situations.
Case example 2: Andy J. is a 55-year-old business
executive. He is fit and active. With a single exception his family
has a history of living well into their 80s. The exception is his uncle
(one of his mother's younger brothers) who died from prostate cancer at
the age of 62, just 12 years ago. Andy has been having regular DREs and
PSA tests since he turned 50. The PSA was almost undetectable until
last year, when it was 3.7 ng/ml. This year his doctor tells him that
his PSA is significantly elevated: 11.4 ng/ml. There is no other sign
of cancer.
Assuming Andy has prostate cancer, chances are he is going to want (and
should have) treatment. There is a family history of prostate cancer.
However, Andy otherwise has a good chance of more than 20 years of life
ahead of him. His PSA value has risen significantly over a short period
of time. A sextant biopsy under ultrasound guidance is probably
essential, and further tests should probably be carried out to attempt
to ensure that the cancer -- if it is cancer -- is confined to the
prostate. Few physicians would consider watchful waiting for Andy.
Now there are going to be patients who are more obvious candidates for
watchful waiting than Chuck P. There will be also be patients who need
treatment even more certainly than Andy J. However, there are also
going to be thousands of people who are somewhere between Chuck and
Andy. How much younger and healthier would Chuck need to be before he
became a clear candidate for definitive treatment? How much older
should Andy be before watchful waiting becomes a reasonable option,
assuming he remains fit and active: 69 years old? 74 years old? 79
years old? Physicians and their patients are faced with questions like
this every day -- and there are no absolute answers.
So what is the controversy?
The controversy is based on divisions of opinion between groups of
physicians about several different sets of data.
In the first place, there are data from Europe (in particular from
Denmark) which suggest that for a very high proportion of patients the
benefit of surgery is, at best, very small. In other words, at least at
a first look, these data appear to indicate that there is little or no
survival benefit from practicing definitive treatment with curative
intent for localized disease. However, these data are easy to criticize
on a variety of levels. Indeed, when they were published in the
Journal of the American Medical Association, they caused uproar
among American urologists because it was felt that the data had been
inappropriately analyzed. It is certainly the case that there were
limitations to the studies published by the Danish investigators.
However, they may have done everyone a favor by making urologists think
harder about which of their patients with localized prostate cancer
really did need definitive treatment.
In the second place, a group of American physicians have been suggesting
for some time that treatment of patients with localized disease offers
only marginal benefit over watchful waiting. (They referred to watchful
waiting as "conservative management.") The data used by this group of
physicians to support their conclusions were analyzed using a relatively
sophisticated mathematical procedure known as Markov modeling.
Unfortunately, Markov modeling is not completely objective. It requires
researchers to make a number of assumptions in order to create and
structure any particular model. When other groups of physicians
reanalyzed these same data while making slightly different assumptions,
they showed a significant benefit in favor of radical surgery as
compared to watchful waiting.
A major clinical trial (the so-called PIVOT trial) has been organized in
order to attempt to resolve this controversy. (PIVOT stands for
Prostate cancer Intervention Versus Observation Trial.) In this trial,
patients are randomized to receive conservative management ("watchful
waiting") or curative surgical treatment. However, some physicians
believe that there are inherent problems with this trial. It may well
be that even when the PIVOT trial is completed, and the results are
carefully analyzed, we still will not know, with any degree of
certainty, whether watchful waiting is any better than radical surgery
when it comes to the treatment of any particular patient with localized
disease.
What is involved in watchful waiting?
Very simply, watchful waiting or active surveillance is a carefully
planned set of actions designed to monitor the perceived progress of any
signs of prostate cancer in a patient who either has prostate cancer
confirmed by a biopsy or who has signs of prostate cancer (e.g., an
elevated PSA level or biopsy proven, high-grade PIN) but has chosen not to have a biopsy.
At the simplest level, active surveillance would comprise regular
check-ups at which the physician would carefully seek signs indicating
increasing progress of prostate cancer (e.g., further increases in PSA
level or increasing hardness or irregularity of the prostate on DRE).
Such regular check-ups might be carried out every 3 or 6 months,
depending upon the views of the individual physician and the comfort
level of the individual patient. Should there be clear signs of rapid
progression of the cancer, there is always the opportunity to take
therapeutic action as appropriate.
Risk/benefit analysis
If, after a diagnosis of localized prostate cancer, you have to decide
whether watchful waiting or definitive treatment is the best option for
you, you need to consider a range of questions and discuss them
carefully with your doctor(s):
- How old are you and how long do you expect to live?
- What is your present quality of life?
- Have you carefully
considered the risks associated with surgery or other forms of
treatment?
- How will you react if you are one of the relatively
rare patients who have long-term incontinence after surgery?
- How
frequently do you really have intercourse now, and with what
degree of satisfaction for all concerned?
- How well will you deal
with impotence (or some form of device for the alleviation of impotence)
if you cannot receive treatment which is guaranteed to avoid this side
effect?
- Can you deal with the possibility that if you don't have
treatment you may be living with cancer for years?
The true "benefit" of watchful waiting is that you do not have to take
any of the risks associated with treatment. The true risk is that you
could be unlucky. You could have a form of prostate cancer that
progresses quickly and, by the time you and your doctor discover this,
the cancer has escaped the prostate and is therefore incurable. No one
can tell you the degree of risk in your particular case. All you can do
is discuss your particular symptoms and test values with your doctor and
try to come to a decision with which you both feel comfortable.
There is, however, one thing worth remembering. You don't have to
make your decision in a hurry. Prostate cancer is a very slowly
growing disease. A couple of weeks or even a couple of months is not
likely to have any effect on the stage of the disease. Make a decision
when you are ready. Talk to your wife or significant other about it.
Learn everything you can before you take an irrevocable step.
For some patients treatment is absolutely the right step; for others it
may be something they simply didn't need to do.
Pelvic lymphadenectomy
[Reminder: this document was last revised in 1997. Procedures may have changed.]
Pelvic lymphadenectomy is frequently carried out prior to further
definitive treatment for localized prostate cancer. It means the
removal of the pelvic lymph glands, which can then be quickly examined
by the pathologist to see whether there is cancer in these glands. The
presence of prostate cancer in the pelvic lymph nodes is a sure sign
that the cancer is no longer localized. In this case there is very
little point in carrying out any form of treatment which is designed for
the management of localized prostate cancer.
Pelvic lymphadenectomy can be carried out using one of two basic
methods:
- There is the option of a separate procedure to remove the
pelvic lymph nodes, which might precede any decision about either
radical surgery or radiation therapy, in which case the method which is
most likely to be used will be "laparoscopic lymphadenectomy," a
technique which avoids a major surgical incision.
- On the other
hand, as the first step in a radical retropubic prostatectomy, the
surgeon will often resect the pelvic lymph nodes and ask the pathologist
for a "frozen section."
In either case, if the lymph nodes are found to be positive, it would be
relatively unusual to decide to proceed with radical surgery. External
beam radiation may, however, be carried out following a discovery of
positive pelvic lymph nodes, since it is possible to include the area of
the lymph nodes in the radiation field. The patient needs to understand
that, in such a case, we are no longer dealing with treatment of
localized prostate cancer: this is locally advanced or possibly advanced
prostate cancer.
Radical surgery
[Reminder: this document was last revised in 1997. Procedures may have changed.]
General overview
The simple objective of radical surgery for the treatment of localized
prostate cancer is the surgical removal of all tissue which might be
expected to include prostate cancer cells, followed by appropriate
reconstruction of the genitourinary system in order to allow normal
urination and intercourse if possible.
Unfortunately, on the one hand, removal of the prostate and other
associated tissues is not a simple operation. It can be complicated by
a whole variety of minor and major problems. It is a highly invasive
procedure requiring deep general anesthesia. In the very worst case
scenario, a very small percentage of radical prostatectomy patients (now
probably less than 1 in 100) die each year during or as a direct
consequence of their surgery. On the other hand, modern surgical
techniques and procedures, and significant improvements in the skills of
urological surgeons over the past few decades, have clearly lowered the
risks associated with prostate cancer surgery. Indeed, many surgeons
are now comfortable carrying out such surgery and sending patients home
within a matter of 3 or 4 days -- sometimes even less.
Careful reviews of large series of prostate cancer patients receiving
surgery at selected centers have now demonstrated relatively high rates
of disease-free survival in patients with organ-confined (localized)
disease for many years with relatively low levels of side effects.
However, many questions still remain, and some of them may never be
properly answered. In the section on
watchful waiting, we have seen that there is controversy
over the relative merits of watchful waiting compared to surgery. Here
are a few examples of other questions which have controversial
aspects:
- Is radical surgery better than, worse than, or
equal to external beam radiation therapy as a form of treatment for
localized prostate cancer?
- What forms of prostate surgery are
most appropriate for which men?
- Which patients should be
receiving so-called "nerve-sparing" prostatectomies?
- What is a
"good" incidence of side effects following radical prostate surgery?
- What is the big disagreement between Dr Stamey and Dr Walsh all
about?
This section will attempt to handle as many of these
issues as possible. However, you should remember, as always, that the
information here is not about you as an individual, it is about general
principles. You will have to discuss your individual case in detail
with a doctor who you trust and respect.
It may be helpful for many newly diagnosed patients to learn from the
personal experience of others. [For a more updated version, see Ron Voss's excellent account as part of his "Handbook."]
The types of surgical intervention
Once the decision has been made to remove the prostate, there are two
basic methods of prostate surgery: radical retropubic prostatectomy and
radical perineal prostatectomy. These names refer to the route which
the surgeon takes in order to be able to remove the organ. Regardless
of the surgical method, there are also a number of options which may be
considered by the surgeon. The surgeon can talk to you about these
options before the operation. However, it is likely that he or she
cannot make final decisions about how to act until the operation is in
progress. The options include
- Nerve sparing in order to attempt to retain potency
- Wide dissection, including cutting through of the neurovascular
bundles, in order to attempt to ensure removal of all the cancer
- Stopping the operation because it is clear that the cancer has
escaped from the prostate.
Radical retropubic prostatectomy
In this procedure, the surgeon cuts down through the abdomen in order to
expose the patient's prostate. In a complex set of procedures, the
surgeon then cuts out as much of the prostate as he or she possibly can.
Ideally, the entire prostate is removed together with the seminal
vesicles. After removal of the prostate and the seminal vesicles, the
urethra is carefully rejoined to the "neck" of the bladder so that on
recovery the patient will be able to urinate in a normal fashion after a
relatively short period of time (usually a few weeks or months).
This is a extremely simplified description of radical retropubic
prostatectomy.
Radical perineal prostatectomy
In this procedure, the surgeon cuts up through the perineum in order to
expose the patient's prostate. While the different surgical route
requires significant technical differences in the manner in which the
operation is carried out, the surgical principles are pretty much the
same as for a radical retropubic prostatectomy.
What is a "nerve-sparing" prostatectomy?
[Reminder: this document was last revised in 1997. Procedures may have changed.]
Until only a few years ago, surgeons considered that any form of prostatectomy was inevitably
associated with subsequent impotence in all but the most unusual (and normally unexpected)
circumstances. Then, in the early 1980s, Dr Patrick Walsh developed
what he describes as a new "anatomical"
retropubic approach to radical prostatectomy.
Using this careful, anatomical approach in carefully selected patients with localized disease, Dr
Walsh demonstrated that it was possible to leave intact one or both of the two "neurovascular
bundles" which pass close to the prostate capsule. In almost all men, these neurovascular bundles
are essential to the ability to have and maintain an erection sufficient for normal intercourse. Thus,
by being able to leave these nerves intact, Dr Walsh was able to remove the patient's prostate while
allowing him to recover his potency following recovery from the surgery.
Dr Walsh and his co-author, Janet Farrar Worthington, have offered a detailed discussion of the
details of this surgery in their book The Prostate: A Guide for Men and the Women Who Love
Them. In addition, this technique is described on the Web in the materials offered by the
Brady Urological Institute of Johns Hopkins. If you want to
obtain the details of this operation, The Prostate Cancer InfoLink believes that it is most appropriate
for you to read about this in Dr Walsh's own words. However, we wish to emphasize two points
which Dr Walsh and Ms. Worthington are very careful to make in their book.
First, "There is no way for the surgeon to know for certain beforehand
whether or not the [neurovascular] bundles can be spared." In other
words, it is only after the surgeon has a clear view of the prostate and
the actual operative situation, that he or she can make the final
decision whether these nerves can in fact be spared. Thus, if you want
to seek a "nerve-sparing" prostatectomy, you must understand up front
that your surgeon may have to tell you immediately after the operation
that such nerve sparing was simply not possible for one or more reasons.
There is absolutely no way that any surgeon can guarantee to
you, before surgery, that he or she can give you a nerve-sparing radical
prostatectomy which will remove all of the cancer. If any physician
makes such a guarantee to you, The Prostate Cancer InfoLink strongly
recommends that you seek a second opinion immediately.
Second (and here we are using the authors' own italics), you must
"Think about what is really important! The primary goal here
isn't to preserve potency, but to get rid of the cancer in a
careful but thorough way." In other words, if your surgeon can preserve
your potency but still leaves you with cancer cells in the area of your
prostate, that was NOT a curative operation, so what was the point?
If you have decided to have surgery, then you need to be certain that
the surgeon will make every attempt to remove all the cancer from your
prostate if he or she possibly can.
Many urologists have learned how to carry out the procedure originally
developed by Dr Walsh. Some of those urologists -- including Dr Thomas
Stamey -- have made modifications to the procedure. However, the
general principles of the operation remain the same. Indeed the very
best urological surgeons who specialize in management of prostate cancer
have probably each carried out hundreds of "nerve-sparing"
prostatectomies since this operation was introduced and generally
accepted.
As a curative surgical technique, nerve sparing prostatectomy, which is
the term most people now use to describe the various forms of Dr Walsh's
original procedure, is strictly limited to patients with localized
prostate cancer. While it would be theoretically possible to spare the
neurovascular bundles in surgical treatment of some forms of
non-localized prostate cancer (a "debulking" procedure), it must be
remembered that since the cancer is no longer localized, the
prostatectomy is not being carried out with curative intent. If it is
not being carried out with curative intent, it is worth asking why it is
being carried out at all.
The complications of surgery
There is a general belief that the complications of surgery may be
highly dependent upon the skills of the surgeon selected by the patient.
If this is true, then it suggests that the patient has some degree of
control over the potential for post-surgical complications if he chooses
a highly experienced surgeon. However, there is at this time no
well-documented and objective evidence to confirm that
complication rates are lower in patients treated by more experienced
surgeons.
Radical prostatectomy is potentially more difficult in a patient who has
had a prior transurethral resection of the prostate (TURP).
It should be recognized that the available information on complications
for any type of treatment for prostate cancer always reflects the
accumulated data of prior years. Thus, since it is generally recognized
that treatment for prostate cancer has gradually improved, it is also
probably true that complication rates today are at least fractionally
lower than the published complication rates.
Having said that, the complications following radical prostatectomy can
include short and long-term urinary incontinence, urethral stricture
(blockage of the urethra which results in difficulty in urinating),
impotence, and the general problems associated with deep anesthesia and
highly invasive surgery. According to a study published in 1993, the
number of patients dying within 30 days of a radical prostatectomy was 2
in every 100 patients. However, the urology community currently argues
that this has been significantly reduced in the past three or four
years. There is no doubt about the fact that morbidity and mortality
rates increase with age, and that they are appreciably higher in men
over 75 years of age than they are in younger surgical candidates.
There is extensive discussion regarding the incidence of post-surgical
incontinence. Individual series from major surgical centers have
reported long-term incontinence in only 6% of patients. However, the
question, "What is incontinence in a post-surgical 65-year-old," has
never been satisfactorily answered. Occasional stress-related urinary
dribbling could be occurring in an unknown but high proportion of
patients who state that they are "continent." This can certainly be
substantiated by case reports in the patient literature. Patients
should be aware that short-term incontinence for several weeks or months
after surgery is close to certain. Equally, serious long-term
incontinence is well documented in a small but significant number of
individuals. In a 1993 survey of Medicare patients who received radical
prostatectomies between 1988 and 1990, over 30% of the patients reported
that they were using pads or other methods for management of
incontinence, and over 60% of the patients claimed that urinary wetness
was (at least occasionally) still a problem for them. Other studies
seem to suggest that at this time there are no significant differences
in rates of urinary incontinence between the patients who receive a
nerve-sparing operation as compared to those who receive standard forms
of radical prostatectomy.
According to at least one report from a major academic center, radical
prostatectomy is probably responsible for at least some loss of sexual
function and potency in all patients. In other words, even if you have
a successful nerve-sparing operation, you should not count on having the
same level of potency after the operation as you had before. It appears
to be generally agreed that in case series from major prostate surgery
centers the percentage of patients who recover sufficient potency for
satisfactory sexual intercourse is between 40% and 65%. However, 60% of
the Medicare patients in the study mentioned earlier reported no
erections since surgery, and 90% said that they hadn't had an erection
sufficient for intercourse in the month preceding the surgery. A report
on the perceived quality of life of men treated for localized prostate
cancer in a managed care setting has suggested that complications as a
result of surgery are common. However, this study encompassed men
diagnosed with prostate cancer between 1961 and 1991; one could
reasonably ask whether its findings are entirely relevant for men
diagnosed today.
How should you choose between surgery and radiation therapy?
[Reminder: this document was last revised in 1997. Procedures may have changed.]
A widely respected urologist based in Norfolk, Virginia, Dr Paul
Schellhammer, is a regular speaker on the comparative values of
radiotherapy and surgery for the treatment of localized prostate cancer.
Dr Schellhammer often shows a slide which describes how often he and his
colleagues recommended surgery or radiation therapy over the past 20-odd
years. This slide shows a series of "humps" which correspond to more
recommendations for surgery or for radiation therapy in any particular
time period.
Dr Schellhammer's point is that we don't know -- in general -- whether
radiotherapy or surgery is the better choice for localized prostate
cancer. Surgical techniques and equipment improve in one year, and then
the next year there are improvements in the techniques and equipment of
radiotherapy. Dr Schellhammer sometimes suggests that there are
"fashions" over time in the treatment of prostate cancer. Like all
fashions, they are the result of uncertainty as to what is the best
thing to do. Maybe in time we will be able to characterize absolutely
which patients are the right candidates for radiotherapy and which are
right for surgery. However, even then, every single patient will be an
individual case and must be considered as such.
On several occasions, attempts have been made to carry out trials which
randomized patients to surgery or radical prostatectomy to try to
resolve the question as to which is the more effective modality. With a
single exception in the 1970s (which has been much debated ever since),
none of these trials have ever succeeded in enrolling enough patients to
get any meaningful results. In the first place, the radiotherapy and
the urology communities have been resistant to enrolling patients into
such trials. In the second place, patients have also been resistant
because they want to feel that they have some input into what is
(perhaps not surprisingly) considered to be an important decision. It
would be wonderful if this issue could, finally, be resolved. However,
The Prostate Cancer InfoLink is doubtful that the necessary trial can
ever be appropriately carried out.
Now there are certain situations in which there is
sufficient information to offer relatively uncluttered guidance to the
patient and his doctor. Here are some examples:
- According to the National Cancer Institute, external beam
radiation therapy is not recommended for patients whose PSA is higher
than 15 ng/ml.
- External beam radiation therapy is not
capable of substituting for nerve-sparing radical prostatectomy. In
other words, if you and your doctor absolutely decide that curative
therapy is appropriate and that it is possible and personally
essential to try to keep your sexual potency for you, then external beam
radiation therapy is not an option because it is associated with
significant levels of impotence in the long term.
- The earlier
and lower the stage and grade of your localized prostate cancer, the
more likely it is that surgery is a superior option for you. This is
because radiation therapy is still inaccurate -- even using the very
latest techniques. Surgery, when properly conducted in appropriate
patients, has a chance of resulting in removal of all cancer tissue
without major long-term adverse effects.
- The later and higher
the stage and grade of your localized prostate cancer, the greater is
the risk that it is not really localized at all, in which case surgery
simply will not work as a curative therapy although radiotherapy
might.
The increasing use of neoadjuvant and adjuvant hormonal therapy in the treatment
of patients with stage T2 prostate cancer may make it even harder to
choose appropriately between surgery and radiotherapy until some of the
current clinical trials have been completed and published. This could
take years. So what is a patient to do?
The most practical suggestion which we can offer is that whenever
possible a patient with a preliminary diagnosis of localized disease
which can be treated with the intent of curing the patient should
try to obtain several opinions before trying to come to any conclusions.
Those opinions should, in an ideal world, probably include the views of
your primary care physician, at least one or two urologists, and at
least one radiation oncologist. Of course it should be added that, if
you accumulate these three (or more) opinions, you may find you are
wiser but that making the choice has become more difficult. We didn't
say any of this was easy!
Seeking and obtaining a second opinion is commonplace among patients
diagnosed with prostate cancer, and is generally accepted by the medical
insurance community. Often one physician will be helpful in enabling
you to secure an appropriate second opinion. It is always useful, if
you can manage it, to obtain at least one opinion from a physician who
will have no financial interest in your subsequent treatment.
When you talk to your physicians, listen to them with all the attention
you can muster. For your own sake, ask them questions if you aren't
absolutely positive about what they are recommending and why. The
important thing is to make the best decision you can with all the
confidence you can pull together. Believing in the decisions you make
with your doctors is a very important aspect of the overall management
of any cancer.
What is the big disagreement between Dr Stamey and Dr Walsh all
about?
Some time ago (September 1994) an academic disagreement between Dr
Thomas Stamey of Stanford University and Dr Patrick Walsh of Johns
Hopkins University became public as the result of an article written by
Dr Stamey and a letter which Dr Walsh wrote to one of his patients in
response to selected comments in the Stamey article. The original Stamey
article and Walsh's
response are accessible on the World Wide Web. This academic
disagreement had been widely known for several years within the urology
community. [The original links to the letters no longer work. However, the material is preserved at Don Cooley's site.]
It is probably not possible on the basis of the available data to
resolve the distinctions between the point of view expressed by Dr
Stamey and the point of view expressed by Dr Walsh. These two surgeons
have, over the past 15 to 20 years, both made outstanding contributions
to knowledge about prostate cancer. In 1995, Dr Stamey received the
highest award of the American Urological Association for his lifetime
contributions to urology. It is almost a foregone conclusion that Dr
Walsh will receive the same award at some time in the future. The fact
of the matter is that Dr Stamey and his colleagues at Stanford and Dr
Walsh and his colleagues at Johns Hopkins are using differing clinical
criteria to compare differing patient outcomes. As a consequence they
have very different results, and therefore very different opinions about
how to interpret those results. Surgery is not like boxing or
wrestling. You cannot put the two surgeons in a ring with two scalpels
and a patient and ask them to fight it out! Unfortunately, that is what
happened in this situation.
It is the carefully considered opinion of The Prostate Cancer InfoLink
that this whole controversy would be better forgotten and put behind us.
At some time in the future, when the technology is better, the
prognostic markers are better, the ability to define impotence and
incontinence accurately is better, etc., etc., we may be able to
rationally address the disagreements between these two academic camps.
At the moment, we can not. Suffice it to say that everyone seems to
have forgotten the final two sentences in Dr Stamey's original article,
which are quoted below. We have added the italic emphasis.
"It is an awesome responsibility for the surgeon to present the
options to a patient with prostate cancer in such a way that he does not
impose his prejudices, which may or may not be based on the best
objective information. I have prepared these comments with the hope
that my own patients will find it easier to make the right decision as
to how their prostate cancer should be treated, regardless of what I
tell them."
These two sentences are perhaps of far greater importance than all of
the rest of the controversy.
The fact of the matter is that Dr Walsh and Dr Stamey agree about
many more major issues than the number they disagree over.
- They agree that surgery for localized prostate cancer is first
and foremost a procedure which is intended to try and cure the
patient.
- They agree that sparing the neurovascular bundles
should only be attempted in those patients for whom this will not affect
the potential ability to remove all of the cancerous tissue in the
prostate.
- They agree that patients with cancer-positive surgical
margins are at very high risk of recurrent prostate cancer.
- They
agree that patients should be very carefully evaluated prior to any
decision about the appropriate method of treatment.
- They agree
that prostate cancer patients should make every attempt to understand
the risks and benefits associated with the different treatment options
available.
Now if you've got this deep into The Prostate Cancer InfoLink, you have
probably worked out that there really are no easy answers for anyone in
the management of prostate cancer. Why should any of us be surprised if
two of the world's leading experts on the surgical management of
prostate cancer have some strong disagreements over how to interpret and
address certain types of clinical and scientific data?
External beam radiation therapy
[Reminder: this document was last revised in 1997. Procedures may have changed.]
Introduction
According to the National Cancer Institute, potentially appropriate
candidates for definitive radiation external beam therapy who have
localized disease are patients with stage T1b or T2 disease. A review
of data from 999 patients treated with radiotherapy indicates that 79%
of T1 patients treated with external beam radiation were alive or had
died of causes other than prostate cancer at 10 years as compared to 66%
of patients with stage T2 disease. The National Cancer Institute also
states that patients with a PSA level higher than 15 ng/ml will probably
fail external beam radiation therapy.
It is important to understand that just as surgical techniques have
evolved in the recent past, so have the techniques of radiation
therapy. Probably one of the most important advances in the most recent
past is the ability to use three-dimensional conformational
planning, which is a method which allows for the more accurate
delivery of the radiation to the prostate, and the avoidance of excess
and unnecessary radiation of surrounding tissues. However, it will be
some years before long-term survival data from radiation therapy with
conformational planning is available. As a result it is unwise to
speculate about the long-term value of this new technique or its impact
on patient outcomes.
In principle, external beam radiation therapy uses a system for the
delivery of high-powered radiation to the prostate and immediately
surrounding parts of the anatomy. The radiation is carefully designed
in so far as possible to kill the prostate and prostate cancer cells.
Various methods have been used in order to try to direct the
radiation accurately to the prostate and to minimize extraneous
radiation of surrounding tissues. As yet, no other form of radiation has
been shown to be as effective in the treatment of prostate cancer as
external beam radiation.
Who should consider radiotherapy for localized disease?
A number of specific type of individuals may wish to external beam
radiotherapy instead of radical surgery for the treatment of their
prostate cancer. And there are certain patients for whom radiotherapy
may clearly represent a better clinical option or may just be a
preferred personal choice.
The most obvious situation in which radiotherapy is clearly a better
option than surgery is for patients who are poor candidates for surgery
because of other medical risk problems. Such patients can be treated
with external beam radiotherapy with good results and low complication
rates and without the risks that come with surgery. Another group for
whom external beam radiation may be an excellent choice is patients who
do not wish to take the risks associated with removal of his prostate.
In either case, the patient should still conform to the recommended
guidelines indicated earlier: stage T1b or T2 with a PSA of 15 ng/ml or
less. It is normal for such patients to be given a bone scan in order
to confirm that there are no signs of metastatic prostate cancer prior
to radiotherapy.
What is actually involved in external beam radiotherapy?
In the first place, the radiation oncologist will carry out a
simulation of your radiotherapy. Depending upon the capabilities of
each individual clinical practice, the complexity of this simulation
will vary. However, the objective is to set up a system which will
ensure the delivery of the most appropriate dose of radiation to a
particular patient's prostate, depending upon the size and position of
that prostate and its location relevant to other nearby organs.
The most sophisticated form of such simulation is "three-dimensional
conformational planning," which is currently available at a limited
number of centers, but will soon become more widespread. Other centers
presently use a variety of x-ray, ultrasound, CT scans, and similar
techniques to plan the delivery of radiation therapy.
Actual treatment can begin shortly after the treatment planning is
completed. A full course of external beam radiation usually takes about
6 and 8 weeks, with a "fraction" of the total radiation dose being
delivered each week day. It takes about 10 to 15 minutes each day to
deliver one "fraction" of the total dose. Unfortunately, it is not
really possible to modify this radiation dosing schedule because of the
way in which cancer cells grow and the way in which radiotherapy acts on
those cells. By delivering the radiation for 5 days each week, the body
is able to recover for two days each weekend.
From a physical point of view, external beam radiation therapy is
relatively easy for the patient. Each day he gets to go to the
radiotherapy center and lie on a treatment table while the radiation
therapist moves a carefully aimed x-ray machine over a targeted area of
the patient's lower abdomen, sides, and back. This is certainly a great
deal less invasive than radical surgery.
Is external beam radiotherapy as good as radical surgery?
This is the $64,000 question to which no one has an answer. As a
patient, the best thing that you can do is carry out your own
risk/benefit analysis and ask yourself some hard questions.
Here are the clear advantages of external beam radiation compared to
surgery:
- There is no surgery and no anesthesia, so there is lower
morbidity and mortality.
- There is no risk from surgical bleeding
and transfusion.
- The rate of impotence resulting from radiation
therapy is generally less than that from surgery.
- Incontinence
rates are generally low (at less than 5%).
- There is good long
term control of the cancer.
On the other end of the scale, there are some clear disadvantages:
- There is a 10-15% possibility of radiation damage to the
bladder and/or the rectum.
- The rate of long-term impotence is
about 30-50%.
- There is a rare occurrence of serious side effects
such as radiation-induced cystitis, proctitis, and enteritis. These are
usually reversible but may be chronic and can occasionally necessitate
surgical intervention.
- Therapy takes 6-8 weeks compared to a few
days.
As with radical surgery, radiation therapy tends to be more difficult in
patients who have had a prior transurethral resection of the prostate
(TURP). According to the National Cancer Institute, definitive external
beam radiation therapy for patients with localized prostate cancer
should be delayed for 4-6 weeks after a TURP because of the risk of
urethral stricture (constriction or narrowing of the urethra).
In the study of patients with localized prostate cancer treated in a
managed care setting (mentioned earlier under the discussion of
complications of radical prostatectomy), radiation therapy was
associated with substantial sexual and urinary problems. However, we
would again note that this study included patients whose diagnosis of
prostate cancer could have been as early as 1961. We would suggest that
external beam radiation treatment for prostate cancer today would be
associated with notably lower levels of adverse reaction than in the
1960s or 1970s.
The question which inevitably is raised by the advocates of surgery is
whether radiation therapy does in fact cure prostate cancer.
Definitive proof that radiation therapy can cure localized prostate
cancer is not available. While PSA levels can be reduced to very low
levels following radiation therapy, the dead prostate cancer tissue
remains in the body (at least for a while). Therefore we do not see the
rapid reduction in the PSA levels to undetectable which can be seen
after radical surgery.
In addition, it appears that while the results of surgery include
disease-free survival as indicated by undetectable PSAs out beyond 10
years, the results of external beam radiation are less reliable based on
PSA data. Control of prostate cancer appears to be approximately
equivalent for about 7-10 years. The question is really whether surgery
can offer benefits over radiation for patients young and healthy enough
to benefit from extended disease-free survival (say 15-20 years), and
then at what cost.
Brachytherapy
[Reminder: this document was last revised in 1997. Procedures may have changed.]
Introduction
Brachytherapy is a form of radiation therapy in which physicians implant
radioactive pellets or "seeds" into the prostate gland in order to kill
prostate and prostate cancer cells. Although there are no data providing
a direct comparison between the results of this technique and any other
form of treatment for localized disease, the data now available from
selected centers would suggest that brachytherapy is potentially as
effective as and may be safer than either radical prostatectomy or
external beam radiation therapy for some patients when carried out
by physicians with appropriate levels of experience.
The great benefit of brachytherapy to the patient as compared to external
beam radiation is that it is carried out in a single procedure, and therefore does not
require the multiple visits necessary for external beam radiation. Having said that,
it should also be recognized that many centers combine brachytherapy with a
short course of external beam radiation in order to offer the best of both
treatment modalities.
At present, the available long-term data on the use of brachytherapy are
limited to 5-7 years of follow-up, which is not sufficient to establish any
true efficacy or safety comparison with other forms of treatment. However,
the availability of new techniques for seed implantation under
transurethral ultrasound guidance, and the availability of new forms of
radioactive seed made with palladium, iridium and other radioactive
elements, which give off low energy forms of radiation within relatively
short time spans, do suggest that in time we may be able to document the
true value of brachytherapy in the management of prostate cancer relatively
soon.
Who might consider brachytherapy?
Patients who are potentially appropriate candidates for brachytherapy
could well include some patients with localized disease.
However, it is hard to tell exactly which patients might be the most
appropriate candidates.
Urologists would probably argue that brachytherapy is
inappropriate for any patient who is a definite candidate for
nerve-sparing prostatectomy, and they have a case. Brachytherapy, like
any form of radiation, is associated with a significant incidence of
post-treatment impotence -- although reliable data are not currently
available for large numbers of patients. On the other hand,
brachytherapy may well be an excellent option for some patients with
stage T1 or T2 prostate cancer because in their cases surgery might
result in positive surgical margins and nerve-sparing surgery is not an
option.
In the end the patient must make decisions about the possible value of
brachytherapy himself in consultation with his doctors. Things which
should influence the patient's decision include:
- Will your insurance cover this procedure?
- How many
brachytherapy procedures has the physician you are talking to carried
out, and what are the short-term and long-term results of those
procedures?
- Does the physician intend to try to cure your
cancer using brachytherapy? In other words, would he expect to be able
to offer you 10 or more years of disease-free survival as a result of
this procedure?
- What is the incidence of short-term and
long-term impotence and incontinence among patients who he has treated
using brachytherapy?
- Can the physician give you references to
two or three other patients who he has treated in the manner he is
proposing for you?
The Prostate Cancer InfoLink suggests that
at this time it is unwise to agree to proceed with treatment using
brachytherapy without seeking at least one other clinical opinion on
appropriate therapy for your individual condition.
How is brachytherapy carried out?
[Reminder: this document was last revised in 1997. Procedures may have changed.]
If you wish to read a detailed description of the procedural techniques
for carrying out brachytherapy, please click
here. [The proposed document was not created before the site closed. For one source on the procedure, click here.]
Side effects of brachytherapy
Brachytherapy has been associated with such long-term adverse reactions
as proctitis (in 1% of patients receiving iodine-125) and impotence (in
about 20% to 30% of patients at 3 and 1 years respectively). In
addition there are multiple short-term side effects such as hematuria
(blood in the urine) and hematospermia (blood in the ejaculate).
However, there are few carefully analyzed data available which offer
objective reports on adverse reactions following brachytherapy. For
example, there appear to be no data on incontinence and diarrhea following
brachytherapy, although these are well-known adverse reactions to
external beam radiotherapy.
The problem of radiation safety
[Reminder: this document was last revised in 1997. Procedures may have changed.]
Although the radiation risks associated with radioactive seed implants
are low, there are certain additional precautions that are important to
know about before you decide to undergo brachytherapy:
- It is possible to pass radioactive seeds in your urine for a
while after the procedure. This means that you have to filter your
urine for a while.
- You are asked to stay at least a few feet
away from young children and pregnant women for a couple of months after
the procedure, so if having your grandson or granddaughter sit on your
lap every evening while you read stories is a big part of your day,
brachytherapy may not be for you!
As you can see, these radiation risks are low risks to others. However,
since they may have significant impact on your lifestyle for a couple of
months they may be important. Brachytherapy could, for example, present
significant problems for a man who shared accommodation with a young
couple with a couple of children and another one on the way.
Cryosurgery
[Reminder: this document was last revised in 1997. Procedures may have changed.]
Introduction
Cryosurgery is not a new technique. Rather it is an old technique which
has been given a new lease on life by the use of improved methods and
equipment. It also has many names. You may find that the people you
talk to about this call it cryotherapy or cryoablation or simply
"cryo."
The basic concept behind cryosurgery is that the cryosurgeon can use
extreme cold to freeze the prostate, which causes the cells to break
down as they are first frozen and then thaw. The freezing process is
accomplished by the use of metallic probes which circulate liquid
nitrogen at -195 F. Modern prostate cryosurgery is usually carried out
by urologists who are very familiar with the techniques of transrectal
ultrasound because ultrasound techniques are used to monitor the
development of the so-called "ice-ball" which grows around the prostate
and associated tissues during this technique.
There are currently many unanswered questions that surround the
potential of prostate cryosurgery. Patients should be aware that this
is not a widely accepted procedure for the treatment of prostate
cancer at the current time. Many experts consider this technique to be
experimental, and The Prostate Cancer InfoLink considers that patients
who wish to be treated by this technique should see if they can do this
within a clinical setting that is dedicated to the accumulation of
greater knowledge about the real value of this procedure. The current
status of this technique also means that there can be difficulties in
obtaining health insurance coverage for this procedure.
The Prostate Cancer InfoLink also recommends that patients consider
cryosurgery only by physicians at centers where there is significant
expertise in this technique. Dr Gary Onik, a recognized authority on the
use of cryosurgery in the treatment of prostate cancer, has provided a
review of current knowledge appropriate for patients in an article
entitled "Percutaneous prostate cryoablation."
The questions about cryosurgery
Certain aspects of cryosurgery are potentially very attractive to
patients and to surgeons. For example, it requires only a brief period
of hospitalization and the patient has an excellent chance of retaining
complete urinary continence almost immediately after the procedure.
However, there is a whole series of unanswered questions:
- Can cryosurgery actually cure prostate cancer?
- Can
cryosurgery actually eliminate prostate cancer cells from the
prostate?
- Should effective cryosurgery reduce PSA to
undetectable levels?
- Can a definitive clinical trial be
developed that will compare cryosurgery to other forms of therapy?
Until at least some of these questions are answered, it will be hard for
the medical community to decide what the precise role of cryosurgery
should be in the management of prostate cancer. However, it does seem
likely that there will be a future role for cryosurgery in the
management of prostate cancer. Some of these will be dealt with in
other parts of this section on treatment.
Can cryosurgery cure localized prostate cancer?
Currently available data appear to indicate that at about 2 years after
treatment at least 20% of patients have a biopsy positive for prostate
cancer and a high percentage of patients have an elevated PSA level.
There are no available data as yet on disease-free survival of patients
who have lived for 5 or more years after cryosurgical treatment.
In order to be sure of a cure for prostate cancer that is localized to
the prostate, it is generally agreed that one must either kill or remove
from the body every possible prostate cancer cell, and the only way to
be sure that this has happened is to kill or remove from the body every
piece of prostate tissue. Unfortunately we cannot be sure that that
happens in cryosurgery.
In order to preserve urinary continence, during cryosurgery the surgeon
places a special catheter into the urethra. This catheter warms the
urethral tissue and prevents it from freezing. However, the result is
that prostatic tissue immediately surrounding the urethra is also
warmed, and therefore is not destroyed by the freezing process. If
there are prostate cancer cells in the prostate tissue immediately
surrounding the urethra, then these cells are unlikely to be destroyed,
so every prostate cancer cell will not be killed.
Now to be fair to the advocates of cryotherapy, not all prostate cancers
include foci of prostate cancer close to the urethra, so there may well
be patients in whom all of the prostate cancer can be destroyed
by this procedure. As usual, however, the question then becomes one of
whether we can tell beforehand which patients are actually the ones most
appropriate for cryosurgery.
Can cryosurgery actually eliminate prostate cancer cells from the
prostate?
It is customary today that before a new medical technique is used
extensively on humans we have learned a great deal about it by
laboratory research work on animals and human tissue. The laboratory
work related to cryosurgery has been relatively limited.
This relative lack of laboratory information does not mean that
cryosurgery will not actually kill or eliminate prostate cancer cells
from the body. However, it does mean that there are all sorts of
unanswered technical questions raised by the scientific and clinical
research community. The lack of answers to these questions makes it
difficult for most physicians to feel that cryosurgery has absolutely
demonstrated its value. This is particularly important if one considers
the use of cryosurgery in localized disease where the intent is often to
cure the patient of his prostate cancer.
Should effective cryosurgery reduce PSA to undetectable
levels?
We know that if radical prostatectomy is to be successful, the patient's
PSA level should be zero or undetectable after the operation. It is
also widely agreed that radiotherapy is much more likely to be
successful if the patient's PSA falls to zero or undetectable levels
after treatment. Is it therefore reasonable to assume that the same
should be true for cryosurgery?
We already know that at least a small amount of living prostate tissue
must be left behind after cryosurgery because of the need to warm the
urethra and the tissue immediately surrounding it. If we leave live
prostate tissue behind, it will be capable of producing PSA. Therefore
it is probably unreasonable to believe that the PSA should fall
to zero. So now we are faced with the question, "How can we tell if the
cryosurgery has been effective?"
Can we develop definitive clinical trials of cryosurgery?
We have never been able to prove that radical prostatectomy or
external beam radiotherapy are effective for the treatment of prostate
cancer relative to each other or any other form of therapy. It
therefore seems highly unlikely that we will ever be able to
prove that cryosurgery is any more or less effective than
cryosurgery or radiation therapy in a randomized controlled trial. The
best that we are going to be able to manage in the short term will be
very careful evaluation of the results from patients treated using
cryotherapy over the next 10 to 15 years. What percentage will have
rising PSA levels over what period of time? How many will die from
prostate cancer after what time periods? Exactly what were the stage
and grade of disease of those patients when they underwent therapy?
Because it is so important to try and find out whether cryosurgery
really does work, The Prostate Cancer InfoLink strongly encourages
patients who wish to undergo cryotherapy to have such a procedure only
at a center which is committed to the careful collection and analysis of
appropriate data about cryotherapy over time. Such a center will
probably want you to come back regularly for PSA checks for the rest of
your life if at all possible, and will want you to provide a very
considerable amount of preoperative information so that they can
establish a sound basis for their research.
Who should consider cryosurgery?
Because cryosurgery is still an experimental technique, this is a very
hard question to answer. However, there are a few definite facts which
should be taken into consideration:
- Cryosurgery does not appear to be successful for patients with
large prostates. If your prostate weighs more than about 40 grams, you
should be extremely cautious before agreeing to undergo cryosurgery.
However, this situation may change as the procedure is refined and
improved.
- Cryosurgery appears to be harder to perform in men who
have already had a transurethral resection of the prostate (TURP).
- Cryosurgery is not a nerve-sparing procedure. In order to
be sure that all of the prostate tissue is properly frozen, most
cryosurgeons will also freeze within the ice-ball the nerves on the
surface of the prostate that are associated with successful erection.
Patients who wish to attempt cryosurgery for the treatment of
localized prostate cancer could include older patients for whom highly
invasive surgery would be a risk or younger patients for whom urinary
continence is more important than sexual potency and the risk of
recurrent prostate cancer.
Complications of cryosurgery
Because ultrasound-monitored cryosurgery is a relatively new technique,
our accumulated knowledge about the complications is limited. However,
here is the available information to date.
Up to 80% of cryosurgery patients are impotent after the procedure, and
it appears that there is a relationship between the degree of impotence
and the way in which the cryosurgeon manipulates the ice-ball in order
to maximize effective freezing of potentially cancerous tissue. The
degree to which patients may be able to recover their potency in the
long term is currently unknown.
Many patients notice irritation to the bladder or the urethra which can
be associated with a variety of additional symptoms, including the
frequent need to urinate with little "warning," a burning sensation or
pain on urinating, or blood in the urine. Some patients also mention
irritation of the rectal wall. In addition, about half of cryosurgery
patients mention penile or scrotal swelling. All of these adverse
reactions appear to be temporary.
There are some less common but potentially serious complications of
cryosurgery. In the first place, some men find that they have scarring
of the urethra and others have difficulty urinating. These problems may
require catheterization on a temporary or perhaps permanent basis. The
most serious complication of cryosurgery is the potential formation of a
"fistula," which is an abnormal connection between the urethra and the
rectum. This requires surgical intervention for treatment.
Neoadjuvant and adjuvant hormonal therapy
[Reminder: this document was last revised in 1997. Procedures may have changed.]
Introduction
There
appears to be an increasing tendency toward combining hormone therapy
with other forms of therapy for the treatment of localized prostate
cancer.
The theory behind this tendency is that by initiating hormonal blockade
before and/or after the primary form of therapy (e.g., radiation) one
(a) delays any progression which might occur prior to implementation of
the potentially curative treatment and (b) in some way or other
maximizes the likelihood that the curative treatment will, in fact, be
truly curative. To what extent these uses of neoadjuvant and adjuvant
hormonal therapy are a result of patient demand, a consequence of
general theoretical belief, or just economic pressure is completely
unknown. However, there are a rapidly increasing number of clinical
trials in development which have been designed to test the validity of
these concepts. Recently, the US Food and Drug Administration endorsed
this form of therapy by its approval of flutamide in combination with an
LHRH agonist and radiotherapy for the treatment of stage T2b and stage T3
prostate cancer.
What are "neoadjuvant" and "adjuvant" hormonal therapies?
"Neoadjuvant" hormonal therapy is hormone therapy which is given prior
to, but in association with, some other form of therapy; for example, a
physician might decide to treat a patient by giving him hormone therapy
before carrying out a radical prostatectomy or external beam
radiation. Similarly, "adjuvant" hormonal therapy is hormone therapy
which is given at the time of or following, but in association with,
some other form of therapy; in this case the physician might decide to
give the patient hormone therapy immediately following a radical
prostatectomy or external beam radiation. Obviously, some patients may
receive both neoadjuvant and adjuvant hormonal therapies.
The most common forms of neoadjuvant and adjuvant hormonal therapies are
the following:
- Neoadjuvant therapy with 1-3 months of an LHRH agonist prior to
treatment with surgery, radiation, or cryosurgery
- Neoadjuvant
therapy with 1-3 months of maximal androgen deprivation (i.e., an LHRH
agonist + an antiandrogen) prior to surgery, radiation, or
cryosurgery
- Adjuvant therapy with 3 or more months of an LHRH
agonist subsequent to surgery, radiation, or cryosurgery
- Adjuvant therapy with 3 or more months of maximal androgen
deprivation (i.e., an LHRH agonist + an antiandrogen) subsequent to
surgery, radiation, or cryosurgery.
- Adjuvant therapy with 3 or more
months of an oral antiandrogen subsequent to surgery, radiation, or cryosurgery.
At least some oncologists and selected radiation oncologists appear to be among the most ardent advocates of
neoadjuvant hormonal therapy, as indicated by the detailed review of this topic
by Drs. Strum and Scholz (Neoadjuvant Hormone Blockade in Prostate Cancer)
and their related article on the informational rights of prostate cancer patients
(A Medical Miranda for the PC Patient).
On the other hand, there are other physicians who have made it clear that
they have grave doubts about many of the current uses of hormonal therapy in
any patients except those with symptomatic stage D2 disease. For example,
Dr Walsh at Johns Hopkins apparently will not operate on any patient
who has received hormonal therapy.
Other pharmaceuticals have also been used in adjuvant and neoadjuvant
settings, including finasteride and diethylstilbestrol (DES). None of
these pharmaceuticals have been indicated by the US Food and Drug
Administration for use in adjuvant or neoadjuvant treatment of localized
prostate cancer.
The Prostate Cancer InfoLink considers that, with the exception of neoadjuvant
and adjuvant maximal androgen deprivation in combination with radiotherapy
for stage T2b and T3 disease, such uses of hormonal
therapy are still investigational. We are awaiting information that shows a
true survival benefit to neoadjuvant and adjuvant therapies for the
prostate cancer patient. We believe that in time such information is likely to
become available. However, it is not available yet. In some cases,
anecdotal information is clear that neoadjuvant therapies have been
offered to patients in order to allow the patient time to deal with
personal issues before undergoing surgery or radiation therapy. Because
prostate cancer is a very slowly growing disease, the value of such
forms of treatment is unknown and may be open to question.
Current clinical data on neoadjuvant and adjuvant hormone therapies
in localized disease
There is very little current data on the use of neoadjuvant and adjuvant
hormone therapy in localized disease. The Prostate Cancer InfoLink is
aware of only two clinical trials from which significant information is
currently available.
In one such trial, the investigators randomized patients with clinical
stage T2b disease to 3 months of neoadjuvant maximal androgen
deprivation with goserelin acetate + flutamide or no prior therapy. All
patients went on to receive a radical prostatectomy. Although this was
a small trial, the results clearly showed that patients receiving
neoadjuvant maximal androgen deprivation were less likely to have
positive surgical margins than the patients who received no neoadjuvant
therapy. On the other hand, the surgeons clearly believed that the
surgery was more difficult and took longer in the patients who had
received the neoadjuvant therapy.
In another, larger trial, the Radiation Therapy Oncology Group (RTOG)
randomized patients with clinical stage T2b, T3, and T4 disease to
receive neoadjuvant and adjuvant maximal androgen deprivation with
goserelin acetate + flutamide or no neoadjuvant or adjuvant therapy.
All patients went on to receive external beam radiation therapy. Again,
this trial has suggested a clinical benefit to the use of neoadjuvant
and adjuvant therapy. However, the data are still unpublished. However, it is on the basis
of this trial that flutamide was recently approved in combination with
an LHRH agonist and radiation therapy for the treatment of stage T2b and T3 disease.
According to data received from Schering-Plough Corp., the RTOG trial
showed the following detailed results:
- Patients receiving hormonal therapy + radiotherapy had significantly
increased median survival (4.4 years vs. 2.6 years) compared to those receiving
radiation alone.
- Patients receiving hormonal therapy + radiotherapy demonstrated a lower rate of local failure
(16% vs. 33%) at 4 years than those receiving radiation therapy alone.
- When normal PSA levels were included as a criterion for disease-free survival,
patients receiving hormone therapy + radiation again demonstrated a significantly
increased median disease-free survival (2.7 years vs. 1.5 years)
We should conclude that while there is some interesting information to
suggest that there are benefits to the use of adjuvant
and/or neoadjuvant hormonal therapy in the treatment of localized
prostate cancer, it is not yet certain that these benefits include extended
overall survival. There are a number of
clinical trials currently in various stages of implementation and
development which have been designed to try to determine whether there
is a real survival benefit to this type of therapy.
The complications of neoadjuvant and adjuvant hormonal therapy
As indicated above, it seem clear that neoadjuvant hormonal therapy
makes radical prostatectomies more difficult for surgeons (at least
when they start carrying out procedures on patients who have received this type
of therapy). As a
consequence, we must seriously question whether pre-treating surgical
patients with maximal androgen deprivation is really worthwhile. The
other risks of neoadjuvant hormonal therapy are primarily the risks
associated with taking the necessary pharmaceuticals for significant
periods of time. Brief comments on the side effects of all of the
relevant pharmaceuticals can be found in the section on pharmaceuticals used in the treatment of
prostate cancer.
Post-surgical radiation therapy
Unfortunately, there is a significant number of patients who,
immediately following surgery, are discovered to have "positive surgical
margins." In addition, there is a second group of patients who are
found to have prostate cancer-positive seminal vesicles. This means that
despite the best attempts of the surgeon, in carrying out the
prostatectomy he or she actually was unable or may have been unable to
remove all of the cancer and there is a good chance that there are
cancer cells left in the tissues which remain. The pathologist can tell
this from a careful examination of the surface of the prostate and the
seminal vesicles after surgery.
Although the patient's disease is still "localized," it is now necessary
to treat the patient in some way in order to try and kill these
remaining prostate cancer cells. It is customary to do this by the use
of adjuvant external beam radiation therapy. While there is no proof
that such adjuvant radiation therapy actually improves survival for
patients with positive margins or positive seminal vesicles, it is clear
that it does reduce the frequency of local recurrence of the disease.
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