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P A A C T,
I N C.
PROSTATE CANCER
COMMUNICATION
P ROSTATE CANCER COMMUNICATION NEWSLETTER • VOLUME 21, NUMBER 4 • December
2005
FOUNDER: LLOYD J. NEY, SR. – FOUNDED 1984
President and Chairperson:
Janet E. Ney
Board of Directors:
Edwin Kuberski
Treasurer
Newton Dilley
Helen Mellema
Peter Noor Jr.
Richard H. Profit Jr.
Anthony Staicer
Honorary Board Members:
Russell Osbun
Frank Perry
Medical Advisory Board:
Richard J. Ablin, Ph.D.
V. Elayne Arterbery, M.D.
Robert A. Badalament, M.D.
Duke K. Bahn, M.D.
Israel Barken, M.D.
E. Roy Berger, M.D.
Michael J. Dattoli, M.D.
Fernand Labrie, M.D.
Fred Lee Sr. M.D.
Robert Leibowitz, M.D.
Mark Moyad, M.D., M.P.H.
Charles E. Myers Jr. M.D.
Gary M. Onik, M.D.
Haakon Ragde, M.D.
Oliver Sartor, M.D.
Stephen B. Strum, M.D., FACP
Donald Trump, M.D.
Steven J. Tucker, M.D.
Ronald E. Wheeler, M.D.
Treatment Options for
Post-Prostatectomy Incontinence
By Gary E Leach, M.D.
Director, Tower Urology Institute for Continence
Co-Director, Center for Pelvic Health,
Cedars-Sinai Medical Center
Los Angeles, CA
Loss of bladder control (urinary incontinence) after prostate surgery is a
devastating complication, which has a significant negative impact on quality of life. The ‘good news’ is that with appropriate evaluation and treatment, the incontinence problem is usually treatable with significant improvement in quality of life.
It is not unusual that lack of bladder control is a problem for the first few
months following radical prostatectomy. A biofeedback program may be
helpful during this time period to help restore bladder control. When urinary incontinence persists more than 3-6 months after radical prostatectomy, appropriate bladder testing, called urodynamics, is used to evaluate the
function of the bladder and sphincter (valve) muscle to determine the exact
cause of the post-prostatectomy incontinence (ppi). This urodynamic testing is performed as a 20 minute procedure in the office. The test involves
filling the bladder through a special catheter while measuring the pressures
in the bladder. During the test, various maneuvers are performed to evaluate the bladder function, demonstrate the urinary incontinence, and thus
specifically define the cause of the urine loss.
Normally, as the bladder fills to capacity, there is very little change in
bladder pressure and the sphincter remains closed allowing the man to stay
dry. When incontinence occurs following prostatectomy, this normal balance of bladder and sphincter function is disturbed.
Our research1 has defined three main causes of ppi based upon urodynamic
findings in men with ppi:
1. High pressure (with ‘spasms’ of the bladder) developing in the
bladder as the bladder fills (50% of men with ppi). These bladder
spasms may cause urge incontinence (the need to rush to get to the
bathroom), frequent urination, and sometimes loss of urine at night.
Let’s Conquer Cancer in OUR Lifetime
2
3
This high pressure bladder dysfunction can
also occur following pelvic radiation therapy.
Damage to the sphincter muscle (35% of men
with ppi). This damage results in stress incontinence with loss of urine during change in
position, coughing, straining, or vigorous
physical activity.
A combination of bladder malfunction and
sphincter damage (10% of men with ppi).
Men with this combined problem usually experience “mixed incontinence” symptoms
with a combination of both urge and stress incontinence.
Treatment Options:
Biofeedback can be a treatment choice in men who
are incontinent and desire treatment early after radical prostatectomy (within the first 3-6 months following surgery). Biofeedback is also a useful treatment
option in men who have more minor degrees of incontinence. The treatment program involves weekly
visits for about one hour per visit with a trained therapist. A special sensor is inserted into the rectum and
attached to the biofeedback computer. During the
treatment session, the patient is taught to contract
CANCER COMMUNICATON
Published Quarterly by: PAACT, Inc.
Patient Advocates for Advanced Cancer Treatments
1143 Parmelee NW
Grand Rapids, MI 49504
and strengthen the pelvic muscles with this muscular
contraction being displayed on the computer screen.
Also, an electrical signal can be sent to these pelvic
muscles to help strengthen the muscles. Each week,
the goal is to make the muscles stronger. Many men
experience significant improvement in bladder control with this biofeedback program.
With treatment directed by the urodynamic testing,
the majority of men are able to experience significant
improvement in their urinary control. When the main
problem is high bladder pressures, medications to
relax the bladder are usually effective. These medicines work by blocking nerve receptors in the bladder. Blocking these receptors results in decreased
bladder contractility. Medicines to relax the bladder
(generally known as anti-cholinergics) include Enablex, Vesicare, Ditropan XL, Detrol LA, the oxytrol
patch, and imipramine. Side effects of these medications may include dry mouth, constipation, and blurry
vision. These drugs should not be used in patients
with uncontrolled narrow angle glaucoma or in men
who do not empty their bladder well. When the oral
medications fail to control the high bladder pressures,
the Interstim “bladder pacemaker” device can be an
excellent treatment option.
INDEX
Page
1. Treatment Options for Post-Prostatectomy Incontinence (Gary Leach, M.D.)
Director…Richard Profit
Editor….Richard Profit/Molly Meyers
Assistant….Molly Meyers
Webmaster….Art Schlefstein
5. When Should You Start Treatment with Ketoconazole? (Mark Scholz, Richard Lam, Brad Guess,
Ralph Blum)
Postmaster: Send address changes to:
Prostate Cancer Communication
P.O. Box 141695
Grand Rapids, MI 49514
8. PSA Evaluations in Hormone-Refractory Prostate
Cancer (Oliver Sartor, M.D.)
Phone: 616/453-1477
Fax: 616/453-1846
E-Mail: [email protected]
PAACT Web Page: http://www.paactusa.org
Newsletter: http://www.paactusa.org
Editor:
Articles authored by other than the editor may not fully
reflect the views of the corporation but are printed with the understanding that the patient has the right to make his own interpretation
of the efficacy of the information provided.
In an effort to conserve space and be able to insert as
much material as possible in the newsletter, references from various
articles are intentionally omitted. If you would like to obtain those
references, please contact PAACT, we keep all of the original articles
and the references used on file.
10. What The Heck Has Been Going On In My
World – Part 9! (Mark A Moyad, M.D., M.P.H.)
14. Everything You Ever Wanted To Know About
Chronic Prostatitis: A Critical Update For The “Sons
of Survivors – Part II (Ronald E Wheeler, M.D.)
21. Acknowledgements
22. Ask Dr. Barken – Free phone in show.
23. Financial
Options for treatment of sphincter damage include
biofeedback, injection therapy (which is generally not
successful), the artificial urinary sphincter, and the
male sling procedure. Those men with “mixed”
bladder and sphincter malfunction undergo initial
treatment (usually with anti-cholinergic drugs) to improve their bladder function (i.e. lower their bladder
pressures) followed by treatment to address the weak
sphincter (if necessary). Commonly, follow-up urodynamic studies are performed to evaluate the response to each stage of therapy.
Interstim “Bladder Pacemaker”
When the usual medical treatments to lower high
bladder pressures are not successful, the Interstim
“bladder pacemaker” may be an excellent alternative.
This treatment involves a “two stage” approach with
both stages performed under local anesthesia as an
outpatient procedure. The first stage involves placing
a special stimulation electrode in the lower back next
to the main nerve that controls the bladder (Figure
1a). This stimulation electrode is placed through a
special needle under local anesthesia without the
need for a large incision. The patient then wears an
external stimulation box connected to the stimulation
wire for 7-10 days as a “test stimulation” to evaluate
the response of the bladder to the electrical stimulation to “relax” the bladder. When a satisfactory response is obtained, we proceed with the second stage
of the procedure, which involves implantation of an
internal ‘pacemaker’ generator that is attached to the
stimulation electrode and programmed through the
skin (Figure 1b). The generator is very similar to a
heart pacemaker with a battery that usually lasts 8-10
years. This second stage is also performed under local anesthesia as an outpatient procedure in about 15
minutes. Overall approximately 50-70% of patients
respond to the first stage trial of test stimulation.
When we proceed with the second stage implant, approximately 85% of patients have an excellent response. Use of the Interstim “bladder pacemaker” is
an effective, relatively “non-invasive” treatment option for those patients who have high-pressure bladder dysfunction who do not respond to the usual
forms of medical treatment.
Surgical treatments of stress incontinence due to
sphincter damage following prostatectomy include
the Artificial Urinary Sphincter (AUS) and the Male
Sling Procedure. In general, injection therapy (i.e.
collagen, Durasphere, etc.) has not been successful in
men with sphincter weakness. This lack of success is
due to the migration of the injected material away
from the sphincter area after injection.
Figure 1a: Interstim stimulation electrode placed next
to nerve that controls the bladder.
Figure 1b: Internal Interstim generator attached to
stimulation electrode.
The Artificial Urinary Sphincter (AUS)
Perfected over the last 20 years, the artificial urinary
sphincter is a device implanted into the body to correct stress incontinence in men with significant
sphincter damage. The AUS has three components: a
cuff that helps close the urethra, a pump placed inside
the scrotum, and a pressure regulating balloon which
is placed in the lower abdomen (see Figure 2). When
the man wants to urinate, he squeezes the pump in the
scrotum, which opens the cuff around the urethra.
Automatically, after 3-5 minutes, the fluid returns
into the cuff allowing the cuff to close. After the device is tested during surgery, the cuff is “locked”
open, and is only activated when swelling around the
pump is gone (usually about 4-6 weeks after surgery).
With the current model of the AUS, long-term patient
satisfaction has been excellent with less than a 15%
mechanical malfunction rate at 7.5 years after implantation of the device.2 Despite these excellent
long-term results, however, some men are hesitant to
have this prosthetic device placed. For these men, as
well as for those with more minor degrees of ppi or
for men who do not have the manual dexterity to
squeeze the pump in the scrotum, the male sling is a
promising alternative.
Figure 2: Artificial Urinary Sphincter in place.
Male Sling Procedure
Over the last few years, the male sling procedure has
become a viable treatment alternative for men with
ppi due to sphincter damage causing stress incontinence. The “best” candidates for the male sling are
men with more minor degrees of stress incontinence
(< 2-3 pads/day), men with no previous history of
pelvic radiation therapy, and men who have not had a
previous AUS inserted. The surgical procedure to
implant the sling takes about one hour and can be
done either on an outpatient basis or with an overnight hospital stay. The purpose of the “sling” is to
compress the urethra and help eliminate loss of urine
with coughing, sneezing, or vigorous activity.
The sling is placed via an incision between the scrotum and rectum. After exposing the pelvic bone on
each side, six titanium bone screws are placed into
the pubic bone (three screws on each side). A permanent suture is attached to each bone screw. These
sutures are then passed through the material used to
create the sling, which will compress the urethra. In
the author’s experience, the most effective material
used for the sling is a specially prepared synthetic
patch which compresses the urethra.
Three sutures on one side are passed through one
edge of the sling and tightly tied. The three sutures
on the other side of the pubic bone are then passed
through the sling and tied to create closure of the urethra at a pressure of 60cm water pressure. This pressure is confirmed by running sterile fluid backward
into the urethra at 60cm water pressure and confirming that this fluid perfusion stops when the sling is
tightened down (see Figure 3). The incision is then
closed. A catheter is usually left in place for 24
hours with most men being able to urinate with good
control immediately after the catheter is removed.
Figure 3: Male sling secured into position.
Thus far, the results with the male sling in properly
selected patients have been encouraging. In one series of men undergoing the male sling, 40% of men
are completely dry, 40% are significantly improved,
and 20% are considered failures. Should the male
sling not be effective, an artificial urinary sphincter
may be considered as a second alternative.
Summary
Recent advances in the evaluation and treatment of
men with incontinence following prostate surgery
have allowed many men to regain their urinary control and improve their quality of life. Men with significant incontinence following treatment for prostate
cancer should have an appropriate evaluation (i.e.
urodynamic testing) to determine the exact cause of
their incontinence. Appropriate treatment based upon
the results of this testing usually results in significant
restoration of bladder control and improvement in
quality of life.
How to Obtain More Information:
Additional information can be obtained on the website: towerincontinence.com. Also, Dr. Leach can be
reached by e-mail: [email protected]
References:
1.
2.
G Leach, B Trockman, and A Wong, et al.: Post-prostatectomy incontinence: urodynamic findings and treatment outcomes. J. Urology
155:1256,1996.
F Haab, B Trockman, P Zimmern, and G Leach: Quality of life and
continence assessment of the artificial urinary sphincter in men with
minimum 3.5 years of follow-up. J. Urology 158:435-439,1997.
When Should You Start Treatment
With Ketoconazole?
Mark Scholz, Richard Lam, Brad Guess, Ralph Blum
Ketoconazole, also known as Nizoral is an FDA approved antibiotic that has an additional effect of
blocking testosterone production. In the 1980’s, when
not used for antibiotic purposes, the drug was primarily administered to men with hormone sensitive prostate cancer, that is cancer responsive to testosterone
deprivation. Subsequently it was discovered that high
dose Ketoconazole (HDK) is effective against prostate cancer even after the development of hormone
resistance. It is HDK’s activity against hormone resistant disease that is of particular interest and the
main topic of this article.
Prostate cancer is not a single disease but a spectrum
of many different illnesses. The more aggressive
types of prostate cancer, particularly the hormone
resistant variants, need stronger therapy, while lowergrade, hormone sensitive forms can be managed with
less toxic agents. Identifying the patients who can
benefit from ketoconazole is just as important as
knowing the methods for its safe administration.
Starting a potentially toxic drug like HDK would be
inappropriate in men with low-grade disease. On the
other hand delaying the initiation of HDK and allowing the aggressive prostate cancer to proliferate increases the risk of treatment resistance.
How delayed treatment results in resistance can be
explained by understanding the biology of cancer.
Most people don’t realize that there are many different types of prostate cancer. Even less well-known is
the fact that several types of prostate cancer can be
present in a single individual. When this is the case,
these different cancers are called clones. The “clonality” of prostate cancer is illustrated by the Gleason
grading system which accounts for the multiplicity of
clones by creating a scoring system incorporating two
grades, the first and second most common clones.
Another important aspect of cancer cell biology is the
genetic instability of cancer cells themselves, which
can result in mutations. The capacity to mutate
means that low grade cancer cells have the potential
to transform into more aggressive clones. More aggressive prostate cancer is defined by two basic characteristics: faster growth rates and the development
of treatment resistance. Mutations converting cells to
more aggressive clones are random events that occur
fairly infrequently. However, when cancer cells increase in number, the probability of a mutation increases. This means that treatment-resistant tumor
clones become more common as cancer progresses.
Gauging the rate of cancer growth has received attention recently as a good way to identify aggressive
variants of prostate cancer. Assessing the rate of cancer growth certainly makes sense as we all know that
some forms of prostate cancer grow slowly and will
never be life threatening. These more benign types of
prostate cancer can be safely watched without treatment. However the same cannot be said for faster
growing variants. Growth rates are measured by PSA
doubling time and PSA velocity. A PSA that doubles
in less than 12 months (for men with relapsed disease) or a PSA that increases more than 2 points a
year (for men with newly diagnosed disease) are both
taken as a reliable indicators for the presence of aggressive prostate cancer.
Between these two aspects of aggressive prostate
cancer--a fast growth rate or treatment resistance-resistance is the more important. A baseball analogy
may convey this concept. Experts in baseball know
that the best pitchers dominate and overpower the
best hitters. Good hitters have the ability to capitalize
on pitching errors when they occur. But skilled pitchers make few errors. In the same way, when an anticancer therapy is working effectively, it stops fastgrowing cancers. The real danger arises when the anticancer treatment stop working.
When talking of treatment resistance, what is the type
of treatment we are referring to? To most men, prostate cancer treatment usually means surgery. But surgery is not the type of treatment we are referring to.
Surgery is not a very effective form of therapy. The
New England Journal of Medicine in September of
2002 published a study showing that 20 operations
were required to save one life. That means only a 5%
improvement in survival at 10 years with surgery.
The success or failure of an ineffective treatment like
surgery cannot reliably signal the presence of aggressive disease.
The type of resistance we are referring to is resistance
to testosterone inactivating pharmaceuticals (TIP),
otherwise known as androgen deprivation or hormone blockade. The pharmaceuticals we are talking
about, just to name a few, are drugs like Lupron, Zoladex, Casodex and Flutamide. TIP is much more effective than surgery. Dr. Messing first reported in
The New England Journal of Medicine in 1999 that
TIP increases 10 year cancer survival rates 58% to
88% in men with cancer spread to the lymph nodes.
This study demonstrates the remarkable effectiveness
of TIP in preventing death even in men with more
advanced disease. The point is that in men needing
treatment because of advancing disease, resistance to
TIP is the best way to identify who should quickly be
switched to a more effective agent like ketoconazole.
Given that TIP resistance creates such a dire situation, what are the signs of its presence? The most obvious sign is a rising PSA despite treatment. Since
TIP functions by lowering testosterone in the blood,
true resistance must be confirmed by a blood test. A
rising PSA with a low testosterone proves that there
is TIP resistance. But a rising PSA with a low testosterone is a more advanced sign of resistance. Resistance needs to be spotted early so that effective
therapy can be started sooner.
An article in the September 2005 issue of the Journal
of Clinical Oncology highlighted a better method of
identifying resistance. The method, called “PSA nadir” operates by determining how low the PSA drops
within 8 months of starting TIP. The authors reported
that in men whose PSA failed to drop below 0.2
ng/ml, hormone resistance developed in 75% of cases. We have been emphasizing the importance of
PSA nadir as the earliest sign of hormone resistance
since 1999 (Journal of Urology). This year we are
submitting data to the American Urology Association
meeting showing further evidence that nadir is important but also that using an ultra-sensitive assay
makes nadir measurements even more accurate. We
have found that accuracy increases to 90% using a
PSA nadir of 0.05 instead of 0.2. In June of this year
we published another study in the Journal of Urology
showing that longer remissions occurred in men with
hormone resistance who were started on HDK with
lower PSA levels. Based on this data we believe the
effectiveness of HDK will be even further improved
if HDK is started before the PSA starts rising, i.e. as
soon as a high PSA nadir is detected.
The mechanism by which HDK functions to kill
prostate cancer cells has been debated for years.
Some have argued that HDK works primarily by fur-
ther lowering testosterone levels. But what has been
confusing is that HDK can induce remission in men
whose testosterone is already low. This capacity
suggests that HDK has some form of direct killing
effect on prostate cancer cells independent of its testosterone-lowering effect. This belief has been supported by studies showing that HDK suppresses the
growth of hormone resistant prostate cancer cells
grown in the laboratory.
Further light was shed on this question of HDK’s
mechanism of action in an article published in the
Journal of Clinical Oncology March of 2004 by Eric
Small. In this study Dr. Small showed that two testosterone-like hormones coming from the adrenal
glands--DHEA and Androstendione (Andro),--were
in the blood at higher levels in men with hormone
resistant disease that responded to HDK therapy
(Andro is the same chemical Mark Maguire is supposed to have taken to hit all those home runs). These
same researchers also reported that resistance to
HDK in men that were previously responding was
signaled by rising levels of DHEA and Andro. This
connection between the levels of these hormones and
HDK effectiveness appears to confirm a long suspected relationship between HDK’s potent hormone
blocking ability and its anti-cancer activity. This
connection, established by Dr Small and his collaborators, also fits logically with other research theories
that have long suggested that resistance to testosterone blockade is not total but only partial. According to this theory, cancer clones thought to be resistant to testosterone deprivation are not truly hormone resistant. Rather these “hormone resistant
clones” are cancer cells with a capacity to grow using
the weaker forms of testosterone like DHEA and
Andro.
Dr. Small’s report indicates that DHEA and Andro
production can resume even when adequate levels of
HDK in the blood have been documented. This can
happen through a process called tachyphylaxis. This
is the same bodily process that occurs when morphine addicts require higher and higher doses of
morphine to get the same pleasurable results they obtain in times past. What happens is that the body
adapts to the morphine, becoming less sensitive to the
drug as time goes on, requiring larger and larger doses to achieve the same effect. The hormones we are
concerned about--testosterone, DHEA, and Andro-are being produced in two different areas of the body,
the adrenal glands and the testicles. How best to
manage breakthrough DHEA and Andro production
from the adrenals, is not known for sure. Possibilities
include restarting HDK after a short holiday period, a
trial of a related agent called Cytadren, or perhaps a
switch to a completely different class of testosterone
blocker, Nilutamide.
for what has been termed the “anti-androgen withdrawal response.” It is true that 10-15% of men experience a transient PSA decline lasting an average of
3 months with this maneuver (the Lupron or Zoladex
is continued). In our experience these responses are
too infrequent and too brief to justify delaying the
initiation of a more effective treatment such as HDK.
Managing testosterone production from the testicles
is a straight forward proposition. Lupron or one of its
many alternatives such as Zoladex, Eligard, or Trelstar, is very effective. Since there is a risk of uncontrolled testosterone production from the testicles during HDK treatment, it is our customary practice to
continue a drug such as Lupron when using HDK to
prevent this from happening.
Over the years we have seen mixed results in men
who have elected to stop HDK therapy after they
achieved a good response and maintained a low, stable PSA. Some of these individuals have responded
well when the PSA started rising and the HDK therapy was reinitiated. In some other cases restarting
HDK proved ineffective. There is no way to know if
a treatment holiday contributes in any way to the onset of HDK resistance.
Other explanations besides tachyphylaxis must be
considered when it appears that HDK is not working.
One possibility is that the ketoconazole is not being
absorbed from the stomach into the blood. This possibility is easily evaluated by measuring the amount
of HDK via a simple blood test. If the level in the
blood is below 1, poor absorption is the most likely
explanation. HDK is absorbed best when taken without food and in combination with an acidic agent,
like vitamin C (ascorbic acid). The typical dose of
ketoconazole is one 200 mg pill every 8 hours increased to two pills every 8 hours if there are no side
effects.
Once HDK has been started, the PSA should be
checked every 2 to 4 weeks to determine whether or
not it is effective. A rising PSA after 30 days does
not invariably mean that HDK will prove to be ineffective with further treatment. We generally recommend waiting 60 days before concluding that HDK is
ineffective. The ultimate goal is a PSA that ends up
declining 75% or more from baseline, since it is this
threshold that has been associated with longer survival. Such declines, when they occur, usually occur
over a number of months. In the study we published
in the Journal of Urology, June 2005 in 79 men with
varying stages of hormone resistant prostate cancer, a
75% or greater decline in PSA occurred 44% of the
time.
It has been argued that in men showing early signs of
hormone resistance, HDK therapy should be delayed
until the results of stopping Casodex or Flutamide
can be ascertained. This is accomplished by looking
Ketoconazole can have a variety of side effects and
drug interactions. The number of potential drug interactions is very extensive and includes most diabetes medications, many allergy medications, blood
thinners, as well as some types of sleeping pills and
certain antibiotics. Careful review of all potential
drug interactions is essential for anyone starting ketoconazole. The most prominent direct side effect of
HDK is fatigue. The degree of fatigue varies from
individual to individual. The best method to minimize fatigue is to maintain muscle strength with a
weight lifting program for at least one hour twice a
week. We have also seen some benefit with the use of
a medication call Provigil, a drug that is FDA approved for the treatment of narcolepsy.
Other common side effects from HDK include stomach and liver problems. Initially, blood tests to check
liver function must be done monthly. If any abnormalities are detected the drug must be stopped immediately. Usually HDK must also be stopped if stomach problems like heartburn develop, since taking
antacids blocks its absorption into the blood stream
making HDK ineffective.
An additional hormone besides DHEA and Andro is
also produced in the adrenal glands. This hormone,
called hydrocortisone, is also blocked by HDK just
like DHEA and Andro. Many of us are aware of the
undesirable effects of excess cortisone which is
sometimes administered in the form of injections or
pills by physicians for the treatment of arthritis,
asthma, and allergic reactions. Excessively low hy-
drocortisone levels can also be dangerous. The first
sign of a low level is significant fatigue. The inability
of the adrenal glands to release extra hydrocortisone
into the blood stream during times of stress is another
danger. For this reason hydrocortisone replacement
20 mg with breakfast and 10mg with lunch is routinely administered. Men taking hydrocortisone should
wear a bracelet so that if they are knocked unconscious, emergency personal know to administer intramuscular hydrocortisone.
The most encouraging aspect of high dose ketoconazole treatment is the possibility of extended remissions lasting for years. If the medication is well tolerated over the first few months it usually continues to
be well tolerated throughout the course of treatment.
We believe that the best results can be obtained by
starting HDK treatment early, before the disease has
time to proliferate, mutate, and produce multiple
treatment-resistant clones. This means that the best
time to start HDK is at the very first sign of hormone
resistance, when the PSA nadir on TIP is greater than
0.05 ng/ml.
PSA Evaluations in Hormone-Refractory
Prostate Cancer
Oliver Sartor, M.D.
PSA is frequently incorporated into the management
of hormone-refractory prostrate cancer (HRPC) patients but is not accepted as an endpoint in clinical
trials by the FDA for drugs that are being tested with
registrational intent. How is it possible that this
commonly used test is not accepted by regulatory authorities and many leaders in the field?
First let us examine some of the imperfections in
PSA. PSA most directly reflects activity of androgen
receptor (AR) activity in prostate cells, and specifically PSA is not a true marker of cell proliferation.
Measurements of PSA are more likely to yield estimates of the total volume of PSA producing cells
which is not the same as the volume of cancer and is
certainly distinct from rate of growth. We know that
any drug (leuprolide, gosarelin, bicalutamide, flutamide, dutasteride, finasteride, testosterone, etc.) that
affects androgen levels or the androgen receptor influences PSA to a significant degree. We also know
that it is folly to over-evaluate changes of PSA when
testosterone levels are changing. It is also critical for
readers to understand that agents that interact with
the androgen receptor (such as the antiandrogens) are
conceptually the same as testosterone or dihydrotestosterone (DHT) lowering agents (see Table 1).
Table 1. Some Drugs and Hormones Affecting Activity at the Androgen Receptor
Hormones
AntiLHRH
5-Alpha
Androgens
Analogues Reductase
Inhibitors
Testosterone Bicalutamide Leuprolide Dutasteride
(Casodex)
(Lupron,
(Avodart)
Eligard)
DihydroFlutamide
Gosarelin Finasteride
testosterone (Eulexin)
(Zoladex) (Proscar)
DHEA
Nilutamide
Triptorelin
(Nilandron)
(Trelstar)
Most importantly, PSA declines have not consistently
been a surrogate for survival, particularly in HRPC
trials. The pivotal TAX327 trial (1) is one case in
point.
In
that
trial,
the
prednisone/dexamethasone/docetaxel every 3 weeks arm
and the prednisone/dexamethasone/docetaxel weekly
arm had essentially similar PSA >50% decline rates
(45% and 48%, respectively) yet only the every 3
week regimen demonstrated a survival advantage
compared to prednisone/mitoxantrone. Despite the
fact that patients with a PSA response had a 60% reduction in mortality risk compared with PSA nonresponders, a careful analysis indicated that only approximately half the treatment effect on overall survival was accounted for by the PSA response as analyzed in that study (2).
The ASCENT trial (3) is another pointed example. In
that trial, PSA declines (>50%) were not statistically
distinct
between
arms
(calcitriol/dexamethasone/docetaxel
versus
dexamethasone/docetaxel), but in the multivariable analysis
survival was favorably impacted in the experimental
arm. It is perhaps relevant to note that the ASCENT
trial is still relatively immature with regards to survival, thus the preliminary conclusions and the final
conclusions could be distinct.
Do these examples mean that PSA is not useful in
HRPC? Perhaps not, there are many ways to examine
PSA changes other than declines of >50%. Surrogates are typically continuous and not binary (4).
Thus simple binary analyses (PSA decline of greater
or less than some arbitrary cut-point) may be suboptimal in attempting to establish best predictive values.
Any measurement of PSA decline that does not incorporate duration may not capture important information. Better information capture may be accomplished by requiring a minimum duration or decline
(for example, 8 or more weeks), by stipulating a
“landmark” analysis time point that conveys some
duration of the response (i.e. 12 weeks after start of
therapy), or by calculating “area under the curves”
which combine information regarding the duration
and extent of PSA decline.
Undetectable PSA nadir is a concept that is increasingly invoked as a critical variable in hormonally
treated patients (5,6). HRPC patients rarely have undetectable PSA nadirs due to the relative inactivity of
current drugs. Highly effective therapies would potentially advance the field of PSA surrogacy as these
agents would potentially permit the role of undetectable PSA to be explored in HRPC (just as viral titer
nadirs have been successfully used in HIV infected
patients after highly active anti-retroviral therapies).
In the presence of highly active therapies, failure to
achieve an undetectable nadir will in all probability
represent a predictor for survival however we need
better therapies in order to test this hypothesis directly.
The importance of PSA kinetics (see Figure 1) are
widely appreciated in earlier stage disease yet PSA
kinetics (such as velocity or doubling time) have yet
to be fully explored in HRPC survival studies. Preliminary data reported by Crawford et al (7) indicate
that PSA velocity measured during the first 3 months
of chemotherapy provides independent prognostic
information to treatment. Oudard and colleagues have
demonstrated that PSA “half time” (another PSA kinetic measure) during chemotherapy is strongly associated with survival (8).
Incorporating time to progression (another variant of
PSA kinetics) in HRPC patients is only now beginning to be explored. An analysis from NCI data recently concluded that PSA progression-free survival
is an excellent predictor of survival (9). Because time
to progression is so critical, it in fact may be a better
predictor of survival than PSA declines. This needs
more exploration.
Though decreases in PSA may be controversial, increases in PSA are not. Most everyone conceptually
agrees that a PSA rise is associated with poor prognosis and thus the percentages of patients with PSA
rise, and the timing of PSA rises, may be appropriate
to carefully examine. It is also important to consider
the rate of rise. Every rise is not equivalent. Those
patients that rise faster do worse.
Taken together, PSA changes, particularly PSA
changes over time, represent a fertile field for additional investigation in patients with HRPC. To dismiss the importance of PSA because it has failed to
perform perfectly in some well publicized studies
may be premature. This potentially important variable is in need of additional and very thorough study
in order to maximize its potential.
References
1. Tannock IF, de Wit R, Berry WR, Horti J et al. Docetaxel plus prednisone or
mitoxantrone plus prednisone for advanced prostate cancer. N Engl J Med. 2004
Oct 7;351(15):1502-12.
2. Roessner M, de Wit R, Tannock IF, et al. Prostate-specific antigen (PSA)
response as a surrogate endpoint for overall survival (OS): Analysis of the TAX
327 Study comparing docetaxel plus prednisone with mitoxantrone plus prednisone in advanced prostate cancer. 2005 ASCO Annual Meeting Abstract 4552.
3. Beer TM, Ryan CW, Venner PM, et al. Interim results from ASCENT: A
double-blinded randomized study of DN-101 (high-dose calcitriol) plus docetaxel vs. placebo plus docetaxel in androgen-independent prostate cancer (AIPC).
2005 ASCO Annual Meeting Abstract 4516.
4. Johnson K, Stokes B, Anthony D, et al. Modeling oncology surrogate markers. 2005 ASCO Annual Meeting, Abstract 9639.
5. Bianco FJ, Kattan MW, Beekman KW, et al. Prognosis after androgen deprivation therapy in men with a rising PSA after prostatectomy. 2005 ASCO Annual Meeting Abstract 4552.
6. Stewart AJ, Scher H, Chen M, et al. The clinical significance of a PSA nadir
> 0.2 to patients with a rising post-operative or post-radiation PSA treated with
androgen deprivation. 2005 ASCO Annual Meeting Abstract 4547.
7. Crawford ED, Pauler DK, Tangen CM, et al. Three-month change in PSA as
a surrogate endpoint for mortality in advanced hormone-refractory prostate
cancer (HRPC): Data from Southwest Oncology Group Study S9916. Journal of
Clinical Oncology, 2004 ASCO Annual Meeting Proceedings (Post-Meeting
Edition). Vol 22, No 14S (July 15 Supplement), 2004: 4505.
8. Beuzeboc P, Banu E, Goubely Y, et al. Corrected area under prostatespecific antigen (PSA) curve and PSA half-time dynamics during chemotherapy.
A new prognostic classification for hormone-refractory prostate cancer (HRPC)
patients. 2005 ASCO Annual Meeting. Abstract 4641.
9. D'Amico AV, Chen M, Cox MC, et al. Intermediate end point for survival for
patients with hormone refractory metastatic prostate cancer. 2005 ASCO Annual
Meeting. Abstract 4553.
WHAT THE HECK HAS BEEN GOING ON IN
MY WORLD-PART 9!!!
By Mark A. Moyad, M.D., M.P.H.
I am often asked what the M.P.H. in my name/title
stands for and some people think it means “Miles per
Hour,” but this is wrong. It stands for “Masters in
Public Health.” Okay, now I feel better - that was my
brief moment of therapy. Next, by the time you read
this article the Michigan and Ohio State football
game will be over, and although Michigan has lost
half of its team to injuries, I still think Michigan will
win. Now, there is little more I can say about this
game because it is the greatest football rivalry in
sports, and anytime I predict scores or mention other
things about Ohio State I seem to get a lot of hate
mail. Therefore, since I have no desire to spend the
rest of my natural born life in the F.B.I. witness protection program I will only discuss more about this
game and really rub it in if we win this year! What if
we lose? I will still support the Big Ten (greatest
conference in the universe) in all bowl games regardless of the Big Ten team that is there (notice how I
capitalized the words Big and Ten).
60) I would like a free booklet on rising PSA while
on hormone therapy. Is there such a free booklet?
I am glad that you asked this question! Yes, several
researchers and patients put together a free color
booklet (more than 50 pages) that talks about everything from hormone therapy side effects, diet, secondary hormonal therapies, chemotherapy, clinical
trials…. LET ME SAY THIS AGAIN - THIS
BOOKLET IS FREE AND ALL YOU HAVE TO
DO TO GET IT IS TO LOG ONTO THE WEBSITE
www.iche.edu and order the booklet. The booklet is
officially entitled “Living with Advanced Prostate
Cancer: When PSA rises during hormone therapy.”
What is the catch??? There has to be a catch? Yes,
there is because you have to get on the internet in or-
der to get this booklet. Otherwise, there is no catch!!
These dedicated patients and researchers devoted a
lot of time in order to make this unique booklet available to anyone that needs it. If you do not have a
computer then just go to the local library, but in my
opinion everyone needs to just GET THE
BOOKLET. Who knows when another booklet or
offer will be made to patients?!
61) Do intensive lifestyle changes impact the progression of prostate cancer?
(Reference: Ornish D, et al. Journal of Urology, September
2005, volume 174, pages 1065 to 1070.)
This was a long awaited clinical study of men that
decided not to have conventional therapy done after
being diagnosed with prostate cancer. A total of 93
men with a PSA of 4 to 10 and a Gleason score of 6
or less were assigned to an intensive lifestyle change
group or control group for 1 year. Keep in mind that
these men did NOT have aggressive prostate cancer.
The average age of these men was between 65 and 67
years of age. The average starting PSA was approximately 6.3 ng/ml, and the average testosterone level
was about 400. The experimental group adhered to
the following lifestyle changes:
-Vegan diet (no animal products and 10% of calories
from fat)
-Soy products (1 serving of tofu daily + 58 grams of a
fortified soy protein powdered beverage)
-Fish oil (3 grams daily)
-400 I.U. a day of vitamin E
-200 mcg a day of selenium
-2 grams/day of vitamin C
-moderate exercise (walking 30 minutes/day - 6 days
a week)
-stress reduction or management (yoga, breathing,
meditation, imagery and relaxation for 60 minutes a
day)
-1-hour support group once weekly
None of the lifestyle change men had conventional
treatment, but 6 of the control patients had conventional treatment. The average PSA decreased 4% in
the lifestyle change group, but increased 6% in the
control group.
The good news about this study is that it was simply
done. You have to give credit to these researchers
and patients. The conclusions of the researchers in
this study were as follows: “Intensive lifestyle
changes may affect the progression of early, low
grade prostate cancer in men. Further studies and
longer term follow-up are warranted.” However, the
editorial comments following the paper were a little
different. Paul H. Lange, M.D. from the University
of Washington called the differences in PSA from the
lifestyle group versus the control group “meager.” I
have no desire to comment on this study except to
say that many researchers thought the study was great
and others thought the results were not so great because despite all the different things these patients
had to do during the study there was not a gigantic
drop in PSA. Regardless, I think everyone agrees
that lifestyle changes before and after a diagnosis of
prostate cancer makes sense and should be discussed.
This is the common conclusion of this important
study. However, the disagreement lies in how much
lifestyle change should be done after being diagnosed
with prostate cancer? Should the changes be moderate or more extreme? This study suggests that the
changes should be more extreme. I am not sure I
agree with this, but I do not have the kind of published research that these researchers now have so
this is a good study to discuss with your doctor. I do
have over a decade of working with prostate cancer
patients on dietary changes after being diagnosed
with prostate cancer, so again, I believe in a more
moderate approach, but stay tuned because there is
more research to come from many different groups
around the country. In the meantime, you can criticize or not the results of this Ornish study, but in the
end you have to give these researchers and patients
credit. They are bringing more attention to lifestyle
changes after a diagnosis and I believe this is a very,
very good thing!!!
62) Aspirin and NSAIDs may reduce the risk of
colorectal cancer, but it comes with an apparent
increased risk of a bleeding event.
(Reference: Nurses Health Study and aspirin JAMA 2005)
The Women’s Health Study did NOT find that a baby
aspirin taken every other day could reduce the risk of
colorectal cancer in healthy middle-aged women over
10 years. However, recent data from the Nurses’
Health Study suggests that it might in larger doses
over a longer period of time. This was a prospective
study of 82,911 women with a 20-year follow-up period, median age of 46-49 years, and 97% of this cohort consisted of Caucasian women. Women that
used regular strength aspirin tablets (325 milligrams)
two or more times per week experienced a 23% reduction in risk compared with women that did not use
aspirin. However, no significant reduction was found
unless women ingested aspirin for more than 10
years. The reduction appeared to be related to the
dosage, but so did the risk of gastrointestinal bleeding. A similar dose-response association was found
for NSAIDs (ibuprofen, motrin…) users. The researchers of this study concluded that the use of regular aspirin for a long-period of time seems to reduce
the risk of colorectal cancer, and NSAIDs have a
similar impact. However, these researchers also
commented that “These results suggest that optimal
chemoprevention for colorectal cancer requires longterm use of aspirin doses substantially higher than
those recommended for prevention of cardiovascular
disease, but the dose-related risk of gastrointestinal
bleeding must also be considered.” The researchers
from this study also did a very good job of putting
these results in perspective by stating, “…use of aspirin at the highest-dose category compared with no
use of aspirin would prevent 1 to 2 cases of colorectal
cancer with an excess of 8 episodes of major gastrointestinal bleeding for every 10,000 person-years.”
Acetaminophen (Tylenol®…) had no impact on colorectal cancer risk, and this finding has also been supported for years from other major studies.
Bottom Line = Regular strength aspirin (325 mg)
used for more than a decade may reduce the risk of
colorectal cancer, but the risk of a major gastrointestinal bleeding event is also increased to a degree
where this side effect risk exceeds the benefit for
many women. Therefore, in my opinion no woman
or MAN should take aspirin for the prevention or
treatment of any cancer without first discussing with
their doctor the risk to benefit ratio.
63) Is the Bird Flu coming to get me?
I do not believe so, but isn’t it interesting that despite
the fact that most infomercials telling the public that
researchers today do not have any of the answers it
seems that we are completely dependent on these
same researchers for giving us an effective medication and vaccine. Have faith in conventional medicine researchers because they are the best hope for
preventing and treating this disease if it becomes a
problem. ALSO, in order to ensure faith in your average conventional researcher please read the information in #64.
64) I could not sleep last night and I saw several
infomercials that told me that conventional medicine is not the answer and that we have made no
progress against disease. Is all this stuff true?
(Reference: Jemal A, et al. JAMA 2005;294:1255-1259.)
(Reference: He J, et al. N Engl J Med 2005;353:1124-1134.)
If you happen to believe some of these infomercials
then I have some valuable swampland in Michigan
that I want to sell you ASAP! Let’s put some things
in perspective for the next time that you have difficulty believing in our so-called “conventional” medicine system. Do you know what the average life expectancy of a human born in the year 1900
was….???? It was about 47 years of age! That’s
right!!! In about one century we have doubled the
average life expectancy!! Now, that is real success.
In fact, a baby born in the U.S. right this second will
have the longest predicted life expectancy of any
previous generation since the beginning of time.
Wow, this is real success! In fact, if you look at just
the years between 1970 and 2002 a real remarkable
trend has been taking place in public health and research in the U.S. The overall age-adjusted death
rate from all causes combined has been reduced from
1242 (per 100,000 per year) in 1970 to 845 in 2002.
In fact, the death rate from stroke has been reduced
by 63%, heart disease death rate has been reduced by
52%, and deaths from accidents have been reduced
by 41%. Recently, death rates from all cancers combined have also begun to decrease. So, then why are
you hearing that there are more people diagnosed and
dying from all major diseases? There is a simple answer to this question. You see, one of the agreed upon risk factors of most major chronic diseases is
simply aging. Yes, aging has become one of the biggest risk factors for most major chronic diseases. For
example; cancer, heart disease, and even diseases like
Alzheimer’s have a common risk factor (aging). The
body gets older and most people have to die of something so of course there are more of these diseases
than ever before, but the average age of death from
these diseases just keeps increasing. So, the infomercials are right in the sense that there are more people
than ever before dying from some of these diseases,
but what they fail to mention is that the average rate
or age of dying from these diseases keeps increasing.
So, come on let’s keep these statistics in their proper
perspective. Of course we need to do a better job of
treating and preventing many diseases, but at the
same time the success of conventional medicine has
been nothing less than amazing. The latest national
report of causes of death also indicated that the death
rate from pulmonary disease has increased, that in
large part is due to smoking, and the death rate from
diabetes has increased, which may also be due in
large part to the obesity problem in this country. Regardless, the average age at the time of death just
continues to increase, which reflects the success of
our system. Some people say, well then why do people in China for example live longer than people in
the U.S.??? Is this really the case?! A recent look at
the causes of death from China found that cardiovascular disease and cancer are now the leading causes
of death in China similar to the U.S. However, when
looking at just the middle-age population in this
country the death rate from cardiovascular disease
and cancer has now surpassed the death rate from
these diseases in the U.S. Therefore, although you
may hear that in some areas of China people are living longer; overall this is really not the case. I get
tired of some infomercials beating up on our medical
system and our researchers because the real statistics
are not really being mentioned. Researchers in this
and other countries are doing a damn good job and
they should be getting more credit. In fact, I have
more confidence than ever before in these researchers. If they receive even more funding I believe we
will continue to see amazing advances in medicine.
So, please contact your local congressperson and
senators and demand more medical research funding
overall. The head of the FDA and National Cancer
Institute (NCI) is a prostate cancer survivor; therefore, the time is more than ripe to demand more funding because I think your voice will be heard. We
tend to forget that recent advances in AIDS research
or advances in breast cancer, or a cervical cancer
vaccine are the result of more research. For example,
you may have heard about the recent advances in
breast cancer with the drug Herceptin®, but this is
the result of researchers receiving more funding. The
time is now to have more confidence than ever in
your researchers, but without serious funding these
individuals can never make the advances that will be
needed over the next few years. Okay, I will now get
off my soap-box!! Just a second!! Before I get off
this soap-box, don’t you find it interesting that some
of these infomercials pretend that they are actually
official interviews rather than an infomercial?! In
other words, if they are attempting to be so scientific
then why are they pretending to be something that
they are not! Who is really getting duped here?! So,
come on if you want to see real advances in medicine
then support those individuals who are really trying
to solve medical problems and not many of the
clowns in the circus of infomercials. Of course, I am
not implying that we do not have problems in our
own conventional medical system, but this is the
same system that has helped to extend life expectancy more than any generation that has ever come before us!!! I believe we really sit at a critical moment
in medical research. Currently, our system not only
has the dedicated individuals, brain power and technology to solve most of our major medical problems,
but without the funding of your local researchers it
will be hard to continue to build on the current level
of success. However, I think that over the next few
years as funding increases we will see treatments improve at a pace that was never imaginable just a few
years ago!!!
65) I hear that vitamin D is a real amazing vitamin, but where do I get this stuff from food or
beverages?
(Reference: Consumer reports 2005.)
Please keep in mind that ultraviolet B light from the
sun is one of the best sources of vitamin D. However, we are a nation on sunscreen and as we get older
the body’s ability to make vitamin D becomes less
effective. Also, obesity seems to reduce the blood
level of vitamin D because most of it gets stored in
fatty tissue. So where can you get vitamin D? First
of all, if you really want to know about your vitamin
D level, please ask your doctor about getting a blood
test for vitamin D. A cheap, low-dose multivitamin
is a very good source of vitamin D and individual
vitamin D supplements and prescription drugs are
also very good sources. However, you should also
keep in mind that eggs, mushrooms and seafood are
the only real natural sources of vitamin D. For example; the average egg contains approximately 25
I.U. of vitamin D. Also, most fish and shellfish contain 100 to 500 I.U. of vitamin D. For example, a
serving of catfish contains about 425 I.U. of vitamin
D, mackerel about 400 I.U., salmon about 250 I.U.,
sardines (yummy) about 230 I.U., tuna in a can about
135 I.U., shrimp about 120 I.U., and mushrooms
about 50 I.U. What about fortified products like
milk? They have added vitamin D, but some of these
fortified products have not been entirely reliable
sources of vitamin D. I realize that many of these
fortified products make certain claims about the
amount of vitamin D, but some research suggests that
some of these products have less than the amount
stated on the label. Regardless, please remember the
saying “eggs, fish, mushrooms, and multivitamins”
because these are some of the better sources of vitamin D. Regardless, if you are really interested in vitamin D or the vitamin D blood test, please talk to
your doctor! Finally, is it true that the darker your
skin color the more sunlight you need to produce vitamin D? This is true, because the darker your skin
the greater the ability your skin has to protect you
from ultraviolet light, but at the same time the more
difficult it is to produce vitamin D.
66) I hear that only really colorful fruits and vegetables should be consumed because they contain
the most antioxidants and nutrients. Is this true?
(Reference: FDA/USDA 2005.)
If you believe this, then again, I have some swampland to sell you in Michigan. All fruits and vegetables have something to offer and I will talk about this
in a later edition. In the meantime, let’s just look at
the poor old piece of celery, which really is not that
colorful and is quite boring in appearance. Just 2
medium stalks of celery contain only 20 calories and
that is a good thing. It also contains zero fat calories,
350 mg of potassium, 2 grams of dietary fiber, 15%
of the daily value of vitamin C, and contains calcium.
Regardless, because it contains a good deal of fiber it
can help to lower cholesterol and make you feel
fuller. The real point here is your diet is supposed to
be fun and easy and I get tired of hearing from the so
called “experts” that some fruits and veggies that are
not that colorful do not have much to offer. This is
silly!!!
HAVE A NICE HOLIDAY AND MAY YOUR
UPCOMING VACATION BE FILLED WITH
FAMILY FUN, EGG-NOG, AND CELERY.
Finally, Mark I heard you are the new editor of a
medical journal by Elsevier called “Seminars in Preventive and Alternative Medicine.” Is this true? Yes,
it is and if you go to the web-site of Elsevier publications (www.elsevier.com or call 1-800-654-2452)
you can order the same medical journal that the
health professionals can use that updates the latest on
diet, supplements, and drugs… for cardiac disease,
different cancers, and anything else that is happening
in preventive and alternative medicine. This is the
end of this shameless promotion until the next issue,
when I will have exciting new news about another
new publication.
Everything You Ever Wanted To Know
About Chronic Prostatitis:
A Critical Update For The “Sons Of Survivors”
PART II
By Ronald E Wheeler, M.D.
THE PROSTATE BIOPSY REVOLVING
DOOR:
The inability to maintain a normal PSA (less than 1.0
ng/ml ideally) will put you in a unique group of men
asked to consider a biopsy of the prostate. Men
unique to this group who fail to stabilize the PSA
(preferably less than 4.0 ng/ml) will become the
hunted. Once the biopsy scheduling (merry-goround) begins, it is difficult to prevent subsequent
biopsies, as anxiety is what drives the process in the
absence of a cancerous result. As doctors, it is important to find disease, seemingly at any cost, in men
who will benefit the most from our therapies. If your
PSA is high (≥ 4.0 ng/ml), your prostate will become
the target of a biopsy needle with virtually any Urologist you meet.
While I might be an exception to the traditional Urologist, there are basic principles that need to be applied when a clinical scenario presents itself as consistent with prostate cancer. In my clinical practice,
men with a non-cancerous digital prostate examination can defer the biopsy when prostatitis is identified
and the preferred recommended treatment course is
followed. Obviously, the Peenuts® prostate nutritional formula is an integral part of the program. The
inability to resolve the degree of disease as determined by a normalized PSA will put us back at
square one where the biopsy makes most sense.
A classic example of a patient’s experience in the
traditional doctor’s office involves a 65-year-old man
from Lubbock, Texas who had noted a PSA of 18
ng/ml. His Urologist appropriately offered and performed an ultrasound examination and prostate biopsy. The biopsy result noted chronic prostatitis with
no evidence of cancer. Antibiotics were ordered despite the lack of a positive culture and sensitivity,
with no other therapy considered. Remember that
less than 5% of cases of prostatitis are actually
caused by bacteria; potentially curable with antibiotics. His PSA was repeated after 6 months and
found to be unchanged. The patient underwent a second prostate biopsy, at the doctor’s insistence,
which again showed only chronic prostatitis. When
the patient asked his doctor what he could do, the
urologist offered to repeat the PSA in another 6
months and consider an additional biopsy at that
time. This is a clinical scenario that is all too common across the United States whereby men are given
no alternative in an attempt to avoid a future biopsy.
I believe, as physicians, we must become better educated regarding relevant scientific concepts that may
radically change the diagnostic or treatment course of
any patient. Far too many men are asked to return to
the biopsy arena over and over, without a well
thought out, patient-friendly strategy or “masterplan.” In this case, the patient was aware enough to
research prostatitis on the Internet. Eventually, he
discovered a nutritional product that improved his
urinary symptoms substantially and reduced his PSA
by almost half, in only 3 months. This was accomplished by merely using an advanced nutritional therapy for the prostate called Peenuts®, which he was
able to purchase without a prescription! While this
patient’s response was outstanding, not all patients
respond identically. The use of the Peenuts® formula is not intended to replace the advice of your
doctor but your thoughts (as the patient); will play
a role in the physician’s decision.
Another equally riveting case involved a 75-year-old
male who had experienced five previous biopsies (all
negative) associated with a PSA of 22.6 ng/ml. Using only Avodart® (Dutasteride) and the Peenuts®
prostate nutritional formula, his PSA dropped to 7.88
ng/ml by the end of 11 months and 5.1 ng/ml at 24
months. Without the presence of prostate cancer,
Avodart® would have been expected to cut the PSA
in half or to 11.3 ng/ml. The improvement to 5.1
ng/ml is exceptional and validates further the benefit
of the Peenuts® nutritional formula related to the
resolution of prostatitis. While this approach likely
shows the benefit of Avodart® and Peenuts® in
combination, the need for additional biopsies is now
gone as the patient’s prostate health status has improved markedly. While further studies with this
treatment protocol are encouraged, the expectation
remains high that similar results will be forthcoming.
“NATURAL THERAPIES” FOR PROSTATE
DISEASE: THE ROLE OF NUTRITIONAL
THERAPIES FOR PROSTATITIS, BPH AND
PROSTATE CANCER
The 5 Keys to Systemic Health include: Proper Diet,
Appropriate Nutrition, Adequate Exercise, Stress Re-
duction, and Education. Not surprisingly, these same
categories are equally important to prostate health.
Regarding the diet, I recommend a modified Mediterranean Cuisine. Specifically, this diet is devoid of
saturated fats associated with red meat and dairy
products. Nutritionally, I recommend the scientifically validated natural product called Peenuts®, taken at 2-3 capsules per day with meals. Additionally,
I recommend Omega-3 fatty acids, based on scientific data that supports the inhibition of known prostate cancer cell lines. This activity takes place with
the daily supplement of Eicosapentaenoic acid and
Docosahexaenoic acid in an appropriate dose. The
need for daily exercise cannot be understated based
on enhancement of the immune system and cardiovascular benefit. Stress reduction is critical to the
avoidance of many illnesses while assisting a strong
immune system. Last, but not least, education will
empower the patient to make improved decisions regarding disease prevention and/or treatment. An extended commentary on the diet will be forth-coming
in my upcoming book, entitled, “Men at Risk: A
Rush to Judgement.”
Beyond the 5 Keys to systemic and prostate health,
natural remedies for prostate related disease are centuries old. The ancient Chinese, for example, used a
combination of Amino Acids, including Glutamic
Acid, Alanine and Glycine successfully, for prostate
maladies. It is not surprising that various remedies
used today contain some combination of these beneficial Amino Acids.
Saw Palmetto (Serenoa Repens, Dwarf Palm), indigenous to Florida valued for its Beta-Sitosterol content, has been revered by some and reviled by others.
Unfortunately, when the data is reviewed, Saw Palmetto does not demonstrate adequate clinical efficacy, in men with prostate related symptoms. In a randomized, placebo controlled, double-blind study,
sponsored by the NIH, Saw Palmetto did not perform
clinically any better than a sugar pill (placebo) at one
year (N = 225 men). Men were evaluated by the
American Urology Association Symptom Index
(AUASI), as the primary study outcome. Additionally, maximal urine flow, post void residual, prostate
size and other health-related issues were assessed.
Take home message: Saw palmetto alone is inadequate to effectively reduce or maintain
prostate symptoms and may actually mask
prostate disease.
To state further, while I personally believe that Saw
Palmetto has synergistic benefit when added to other
ingredients, it may mask disease recognition, when
used alone, by improving slightly the only signal
(sign or symptom) a man may have that a problem
exists. Specifically, men commonly look to Saw
Palmetto when there is any sign of urinary difficulty.
As many men “self-treat the symptoms,” any mild
improvement (placebo or real) will commonly delay
a doctor visit, but more importantly, miss an opportunity to assess prostate health, through a Prostate
Specific Antigen (PSA) blood test. The need for a
PSA at the time men have urinary symptoms cannot be understated, as prostate disease is the #1
health risk that men face.
This should not turn into an opportunity lost. The
PSA test will serve as your baseline from which to
compare others. An additional reason to get a PSA
beginning at age 30-35 is based on the fact that it is
not uncommon for men to have prostate disease in an
absence of any voiding symptoms. (To order a PSA
“Diagnostic Home Kit,” please contact our office
(toll free) at 1-866-PSA-CHEK (772-2435).
While I endorse natural remedies for prostate disease
that can be validated, independent of generic ingredient claims, men should choose a product or formula
that works versus prostatitis primarily. While 50%
of 50-year-old men will have prostate enlargement,
virtually all men, at this age, also have prostatitis as
noted through an evaluation of voiding symptoms
and EPS (expressed prostatic secretion). Specifically, data presented at the NIH in 1999 showed that
81% of men less than 50 years old, with any level of
urinating symptoms, had prostatitis (n = 83), while
88% of men aged 50 or older had prostatitis (n =
152), as judged by the EPS.
Take home message: Voiding (Urinary) symptoms represent non-bacterial Prostatitis, until
proven otherwise, in men of any age, notwithstanding the possibility that prostate enlargement may also be present.
Because prostate enlargement begins in most men by
their mid-forties, it would appear likely that multiple
disease processes play a role in a male of this age.
Despite the controversy, there are few, if any, dependable, disease-altering natural remedies for prostate enlargement.
Much of the older historical data suggests a role for
Saw Palmetto (Beta-Sitosterol) as a product that
blocks the conversion of testosterone to Dihydrotestosterone (DHT). If this were true, the PSA blood
test would be altered (cut in half) by using Saw Palmetto. This does not occur, as independent studies
performed by Marks & Gerber showed no effect of
Saw Palmetto on PSA, at six and twelve months, respectively. If men are interested in shrinking the
prostate size, I would refer them to an FDA approved
product called Avodart® (Dutasteride). This product
blocks the enzyme 5-Alpha Reductase, causing the
prostate to shrink in size by 20-30%. Men are encouraged to ask their doctors about this option and
should remember to multiply the PSA result by two,
to provide an accurate number.
Saw palmetto may mask prostate disease and is
ineffective in reducing the size of the prostate
or PSA, and therefore, does not act clinically as
a 5-Alpha Reductase Inhibitor (5-ARI).
WHY PEENUTS® QUALIFIES TO BE YOUR
PROSTATE NUTRITIONAL FORMULA
Peenuts® is a unique formula with a unique name.
While the name suggests many things to many people, it is an acronym that stands for “Power to Empty
Every Time while Never Urinating Too Soon.” It is
also a name you will not likely forget. In effect, the
name stands for normal bladder function and expected prostate health. Arguably, this formula is the
most studied natural formula in the world. In a randomized, double blind, placebo controlled study performed in 1997, Peenuts® demonstrated improved
ability to decrease the signs and symptoms associated
with an enlarged prostate or prostatitis. The findings
were statistically significant. More importantly, the
findings were clinically significant; meaning…the
patient was able to recognize the improvement.
While all men in the study on Peenuts® improved
their voiding symptoms, 69% of men improved either
6 or 7 out of 7 categories measured (Please refer to an
IPSS-Index or AUA Symptom Index). In a follow-up
to the study, more than 300 men have been evaluated
with similar results in the clinic setting. The average
improvement in the urinary symptom score was 11
points. The PSA, “the barometer of prostate
health,” improved in all patients by an average of
49%, while the EPS, our most sensitive marker for
prostatitis, noted a 66% reduction in white blood
cells (consistent with a reduction in inflammation).
There were no side effects or drug interactions noted
during testing or clinical follow up.
The Peenuts® patented formula consists of:
Vitamin C, Vitamin E, Vitamin B6, Selenium,
Zinc, Echinacea, Glycine, Alanine, Glutamic Acid, Saw Palmetto, Pygeum, Pumpkin Seed, Nettle,
Garlic and Ginkgo Biloba.
Peenuts®, a complex, synergistic blend of natural
ingredients, (comprised of antioxidants, antiinflammatories, beta-sitosterols, and immune boosters), is patented to reduce the PSA (associated with
inflammation), reduce urinary symptoms and reduce
the white blood cell count in the EPS. The mechanism for PSA reduction is based on the formula’s effectiveness versus prostatitis as a cellular oxidative
event while validated by a proven reduction in EPS
as the diagnostic measure of inflammation. Men
should exercise caution when comparing Saw Palmetto and Beta-Sitosterol related products (formulas)
that speak to the intention to assist a healthy prostate
and a prostatitis formula. Notwithstanding an apparent benefit from Beta-Sitosterol (the active ingredient
in Saw Palmetto) on urinary symptoms (real or placebo effect), all prostate formulas are not created
equal. In the process of application for European Patent recognition, I was asked by the European Patent
Judges to compare the Peenuts® formula to a patented BPH formula. The intent of the study was to
judge the benefit of both products regarding prostate
inflammation (as judged by white blood cells in the
EPS). To state further, the Patent Judges needed to
see a difference in clinical outcome unique to the
Peenuts® formula that was not seen with the previously patented BPH formula. After four months, of
an open label study, a comparison of the EPS noted a
68.2% reduction in white blood cells with the Peenuts® formula while the BPH formula had no effect
on the inflammation marker. While this study does
not negate the benefit of the BPH formula to prostate
health, it is doubtful; there is a benefit versus prostatitis. To reiterate, the only way to accurately assess
inflammation of the prostate and the clinical benefit
of the nutritional formula you currently use is to
evaluate the Expressed Prostatic Secretion (EPS).
Failure to do so creates more confusion while questioning the goal of your nutritional supplementation
program.
Take Home Message: Ten or greater white
blood cells in the prostate secretion, obtained at
the time of prostate digital examination and
massage, evaluated microscopically under 400
power, establishes the diagnosis of prostatitis.
In the event a vigorous prostate massage fails to yield
an adequate specimen at the tip of the urethra, doctors are encouraged to use the patented dipstick technology on a post-massage urine specimen, to validate
the disease process of prostatitis. While this methodology is not as accurate as the EPS, it will serve as
an effective diagnostic indicator in the more severe
cases of prostatitis.
Take Home Message: PEENUTS® is an effective, natural compound guaranteed to lower the
PSA in the absence of Prostate Cancer, based
on validated studies and a patent.
Beyond Saw Palmetto, other sources of sterols (primarily Beta-Sitosterols) include Pygeum Africanum
(bark of the African Plum tree), pumpkin seed, sugar
cane and nettle. None of these sterolic compounds
have been validated to benefit men with prostatitis,
as qualified by a numerical reduction in the white
blood cell count, associated with the EPS. On the
other hand, improvement in urinating symptoms has
been reported. Nutritionally, zinc may play a role in
the evolution of prostate cancer as most studies show
prostate tissue levels of this mineral to be low or absent in prostatitis and prostate cancer. The exact relationship has yet to be scientifically elucidated.
Despite the historical data on the potential benefit of
these ingredients, the majority of American doctors
have shown a decided reluctance to embrace natural
remedies for prostate health, without meaningful clinical trials with compelling data. The research of the
late William Fair, M.D., Memorial Sloan-Kettering,
Katz, Moyad, Lowe, Klotz, and others in the supplement arena continues to set the standard and challenge the industry to provide evidence-based facts.
Despite the fact that the FDA has little control
over natural products, no one benefits when false
claims are made. It is for this reason that all nutritional products or formulas should welcome the constructive criticism of others, but on the other hand,
medical journals and the media have an obligation to
report on true breakthroughs of academic and clinical
thought.
In regard to Prostate Cancer, Selenium supplementation, at 200 mcg daily, has been shown to decrease
the incidence of Prostate Cancer by 66%, in a 10-year
study. Likewise, Vitamin E, at 50 mg daily, was
shown to decrease the incidence of Prostate Cancer
by 32% (Alpha-Tocopherol/Beta-Carotene Study). It
is interesting to note that the Vitamin E findings were
demonstrated in a group of smokers. Notwithstanding the data, it is unknown what effect smoking has
on the development of Prostate Cancer, independent
of Vitamin E. The National Cancer Institute (NCI)
intends to answer the questions related to the benefit
of Selenium and Vitamin E in the evolution of Prostate Cancer, in a large scale 12-year study (start date
in 2002). Dubbed, the SELECT Trial, patients will
be randomized to Selenium 200 mcg, Vitamin E 400
mg, Selenium E, and Vitamin E in combination, and
placebo taken on a daily basis.
Based on recent research, there is some concern for
toxicity of Vitamin E in excess of 400 mg daily.
How this will affect the outcome of the NCI study, as
it is moving forward, is unknown, but individuals
should be aware that 400 mg may be toxic to the
heart in supplement form. Beyond the potential toxicity of Vitamin E, there is also concern for toxicity
of other vitamins and minerals, including, but not
limited to, Zinc, Calcium, Vitamin A, Vitamin D,
Vitamin C and Vitamin B6. When the dust settles on
all the issues of toxicity, the most prevalent thought
involves taking nutrients in appropriate doses, but
more importantly, in moderation. Regardless of
what anyone says, more is not better, when it
comes to nutritional supplementation.
FINAL THOUGHTS:
To declare your prostate healthy, your PSA must be
less than 1.0 ng/ml with a complete absence of urinary symptoms; To Check your PSA in the comfort
of your home, call today for your PSA “Diagnostic
Home Kit” – Toll Free: 1-866-PSA-CHEK (7722435).
A PSA of ≥ 1 likely indicates an unhealthy prostate.
It’s obvious that the lower the PSA, the lower the risk
of prostate cancer. Anything you can do to lower
your PSA level will likely reduce your risk of eventually getting prostate cancer.
Keep track of your PSA level for your own records.
The risk is too high if you do not! If your PSA is
between 1.0 – 4.0 ng/ml, there is a 20-30% chance
prostate cancer exists. Likewise, if your PSA is between 4.1-10.0 ng/ml, there is a 20-30% chance that
prostate cancer is present. Given this data, the
healthiest number for your PSA is less than one; remembering that prostate cancer has been reported
with a PSA of less than one, as well, but the odds of
not having cancer with such a low number are in your
favor.
Have your PSA and rectal examination performed
regularly, usually at least every year for men 30-35 or
older. Men at greater than average risk for prostate
cancer, such as Blacks and men with a positive family history of prostate cancer should be checked yearly
starting at age 30. Men with known elevations in
their PSA levels and those with inconclusive or “suspicious” previous biopsies may need to be checked
more often. (Figure 5)
Don’t be afraid to ask questions of your physician or
get a second opinion about your health. A true professional will take the time to answer your questions
and be open to suggestions about alternative therapies
(after all, chances are the traditional therapies have
not worked at this point, if you are reading this article).
Research from the American Association of Cancer
Research (AACR) and others indicate the link between prostatitis and prostate cancer is real! Practically all men with prostatitis will eventually get
prostate cancer (if we live long enough) as the diseases are commonly found together. Remember,
understanding prostatitis is your best first step to
helping yourself.
Learn all you can about prostatitis and treat it as aggressively and effectively as possible. Peenuts® may
be your best first opportunity to establish and/or
maintain prostate health and may delay or even prevent the development of prostate cancer. Validation
will be identified by any combination of biologic disease marker improvement, as determined by a decrease in PSA, a decrease in EPS and/or a decrease in
Urinary Symptoms.
Be aware that your physician may not be an expert on
the treatment of prostatitis. Ask him about the vari-
ous diagnostic tests and therapies available and which
ones are appropriate for you.
For more information on Peenuts® and other nutritional products for the prostate, call Preferred Health
Resources at 1-888-733-6887 or log onto the Peenuts® website at www.Peenuts.com Also, check out
the National Institutes of Health (NIH) Website
(www.nih.gov) for more general information on
prostatitis and prostate cancer research.
Men Who Should Consider Peenuts®
Prostate Nutrition
• All Men with a Family History of Prostate Cancer, Regardless of Age, Have a 10% Increased
Risk for Prostate Cancer
• Men with Known Prostatitis Regardless of Age;
Prostatitis is Associated with All Cases of Prostate
Cancer
• Men with Voiding Symptoms – Voiding Symptoms represent Prostatitis until Proven Otherwise.
In a study of 235 Consecutive Men, with Voiding
Symptoms, More than 80% had Prostatitis, Regardless of Age. This is a Landmark Finding Not
Seen Before in the Literature.
• All Men with PSA Elevation ≥ 1 ng/ml; The
Normal Range for PSA of 0-4 ng/ml is Incorrect;
0-4 ng/ml Cannot Be Normal when 30% of All
Prostate Cancers are in This Range, A True Medical Oxymoron!
• All Men Who Have Undergone Prostate Biopsy
Noting Negative Evidence of Prostate Cancer and
a PSA ≥ 1 ng/ml
• All Men Younger than 30 who are Admittedly
Proactive; One Capsule a Day May be Appropriate if Negative Symptoms and a PSA of < 1 ng/ml
is Identified in Association with a Normal EPS
• All Men Who Have Failed to Be Cured by Traditional Antibiotic Therapy Who Note Continued
Voiding Symptoms and/or a Rising PSA
• Men Who are Presently Taking Proscar (Finasteride) and are Not Comfortable with a Chemical
that Works Minimally Versus Urinary Symptoms
(PLESS Study), yet Costs Significantly
• Men Who Take Alpha-Blockers such as Hytrin,
Cardura, and Flomax; These Products Have Side
Effects and Do Nothing to Improve the Health of
the Prostate
(Figure 5)
EDITORIAL COMMENT
By Stephen W. Leslie, MD FACS (Urologist)
The widespread incidence of prostatitis is well known
to urologists and other doctors, but its association
with prostate cancer has previously been considered
incidental. In this article, Dr. Wheeler has suggested
that prostatitis may actually cause prostate cancer
based on evidence supportive of inflammation leading to cancer consistent with a number of other organ
cancers, the research of the American Association of
Cancer Research, David Bostwick and others. While
the association alone between these two conditions
falls short of being considered definitive, it is certainly plausible and deserves more study. Even a limited
causative link between prostatitis and prostate cancer
would cause a dramatic change in our attitude and
approach to prostatitis.
Currently, prostatitis therapy consists primarily of
antibiotics, alpha blockers and other drugs. The article correctly points out that these remedies are often
inadequate. Dr. Wheeler recommends considering
nutritional agents in the absence of successful definitive therapy. Although nutritional therapy has been
widely used and studied in Europe, it is not routinely
recommended by many U.S. physicians for a number
of reasons. Nutritional therapy is not taught in most
U.S. medical schools and many American physicians
are unfamiliar with the available scientific research
on the subject. Published studies on nutritional therapy are criticized for using different preparations and
dosages, having too small a sample size with limited
numbers of participants, being of inadequate duration, and bias in the selection of patients to be tested.
Commercially available nutritional therapies are usually not manufactured to a pharmaceutical grade
standard, which means each bottle, even from the
same company, may have different biological effects.
There is no universally accepted dosing schedule for
many of these natural remedies and their mechanism
of action is often unknown. Further, no specific
combination nutritional product for either prostatitis
or symptoms of prostate enlargement has ever been
properly tested in a well designed, scientific study.
Dr. Wheeler describes a study he performed at The
Prostatitis & Prostate Cancer Center on a unique
combination nutritional therapy called Peenuts®. He
reports outstanding objective and clinical results, but
the scientific details of his research need to be care-
fully reviewed and his finding duplicated by other
medical experts. If further research indicates he has
indeed found a safe and highly effective therapy for
the signs and symptoms of prostatitis and prostate
enlargement, this would be a major contribution to
the health and well-being of American men while
saving the health care system tens of millions of dollars. Further elaboration of the prostatitis to prostate
cancer model would qualify as a major medical
breakthrough. Minimally, Dr. Wheeler’s research
offers a patented formula with little downside with a
potentially tremendous upside for motivated men.
Benefits of Taking Peenuts®
(The Premier Prostate Nutritional Formula)
A Nutritional Guide at a Glance
• Antioxidants – Benefit in Fighting Free Radicals
and are Synergistic to the Formula
• Immune Boosters – A Unique Combination is
Vital to Allowing the Body to Heal Itself
• Vitamin E and Selenium are Synergistic AntiOxidants and Boost the T Cells
• Vitamin E – 32% Fewer Prostate Cancers noted
in the Finnish Study (ATBC Study), using 50 mg
daily
• Echinacea – A Mild Immune System Stimulant
is Synergistic to the Formula
• Zinc – An Immune Booster that is Low to Absent in Men with Prostatitis and Prostate Cancer
• Selenium: 66% Fewer Prostate Cancers Versus
Placebo (L Clark, PhD)
• Natural Antibiotic – Garlic Works to Improve
the Host Response to Inflammation, Working in
Synergy with All Other Ingredients
• Anti-BPH Ingredients – Saw Palmetto, Pygeum,
Stinging Nettle (also a Source of Vitamin E) and
Pumpkin Seed (also a Source of Zinc) are All
Synergistic
• Ginkgo Biloba – Nature’s Vascular Stimulant
• Amino Acids – Glutamic Acid, Glycine, LAlanine Represent the Chinese Remedy to Prostate Health
• B6 – Assists the Metabolism of other Ingredients
IPSS – INDEX
AUA (BPH) SYMPTOM SCORE
Patient:_______________________
Not At
All
Less
than 1
time in
5
Less
than
half the
time
About
half the
time
More
than
half the
time
0
1
2
3
4
5
0
1
2
3
4
5
0
1
2
3
4
5
0
1
2
3
4
5
0
1
2
3
4
5
0
1
2
3
4
5
None
1 time
2 times
3 times
4 times
5 or more
times
3
4
5
Date:________________________
INCOMPLETE EMPTYING
1. Over the past month, how often have
you had a sensation of not emptying your
bladder completely after you finished urinating?
FREQUENCY
2. Over the past month, how often have
you had to urinate again less than 2 hours
after you finished urinating?
INTERMITTENCY
3. Over the past month, how often have
you found you stopped and started again
several times when you urinated?
URGE TO URINATE
4. Over the past month, how often have
you found it difficult to postpone the urination?
WEAK STREAM
5. Over the past month, how often have
you had a weak urinary stream?
STRAINING
6. Over the past month, how often have
you had to push or strain to begin urination?
URINATING AT NIGHT
0
1
2
7. Over the past month, how many times
did you most typically get up to urinate
from the time you went to bed at night until the time you got up in the morning?
SYMPTOM SCORE: 1-7 Mild, 8-19 Moderate, 20-35 Severe
Almost always
TOTAL:__________
BOTHER SCORE DUE TO URINARY SYMPTOMS
QUALITY OF LIFE DUE TO
URINARY SYMPTOMS
How would you feel if
you had to live with your
urinary condition, the way
it is now, for the rest of
your life?
Delighted
Pleased
0
1
Mostly Mixed
Mostly
satisfied
dissatisfied
2
3
4
Unhappy
Terrible
5
6
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(YOUR NAME WILL APPEAR BELOW IF WE RECEIVED YOUR DONATION BETWEEN THE ABOVE DATES)
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FINANCIAL SUMMARY REPORT
(January 1, 2005 through September 30, 2005)
GENERAL
FUND
1,451,350.83
Balance on Hand December 31, 2004
REVENUES RECEIVED Membership Contributions
Memorial Income
Legacies & Bequests
Investment Income
Total Revenues
57,927.44
8,473.00
42,818.00
43,241.51
152,459.95
Total Balance on Hand and Revenues
EXPENDITURESEmployee Wages
Payroll Taxes
Medical Insurance
Outside Services, Labor
Rent
Meals, Motel, and Transportation
Auto Expense
Printing
Postage and Delivery
Telephone
Service Fees
Maintenance & Repairs
Office and Computer Supplies
Miscellaneous
Total Expenditures
1,603,810.78
Balance on Hand September 30, 2005
1,468,820.25
Assets:
Checking Account
Petty Cash
Saving Account
Certificates of Deposit, Stocks, and Bonds
Money Market Funds
Equipment
39,131.27
50.00
29.63
1,688,671.30
164,500.61
27,028.55
1,919,411.36
Net Assets:
Foundation Fund Balance
56,686.14
6,190.49
18,170.50
2,926.14
9,000.00
2,024.88
1,325.09
17,797.94
16,041.99
1,951.64
1,106.28
135.00
1,246.98
387.46
134,990.53
328,151.40
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Telephone HM:
Birthdate:
St/Province:
WK:
/
/
Postal Code:
Fax:
E-Mail:
Other:
Annual Membership Classification
_____Patient………………….…………...$50
_____Donor………….………………………$500
_____Advocate…………..……………..…$50
_____Sponsor……………..………………..$1000
_____Professional………….…………....$100
_____Corporate…….……...………………$1000
_______Other………..………………………………………………….………...$________
_______Include me as a PAACT member, though I currently cannot contribute
Tribute gifts support the daily operations of PAACT, Inc., by furnishing PC patients, doctors and advocates with the latest
information available on the methods of detection, diagnostic procedures, evaluation and treatments for prostate cancer.
We also participate in matching gift programs and United Way. For more information contact us at( 616) 453-1477.
□ Check Enclosed
□ Charge to my credit card (below): □ MC □ VISA □ Discover □ American Express
Enclosed is $ ________________________________________________, a gift to the Lloyd J. Ney, Sr. Memorial Fund.
Enclosed is $ ________________________________________________, for PAACT’s general operation expenses.
Enclosed is $ ________________________________________________, I wish to remain anonymous.
In Memory of ___________________________________________________________________________________________
Please send acknowledgement card to:
Name __________________________________________________________________________________________________
Address_________________________________________________________________________________________________
City_________________________________________________State____________________Zip________________________
Account Number: ________________________________________________ Amount $ _______________________________
Signature: ______________________________________________________Expiration Date: ___________________________

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