Take One!
PROSTATE
CANCER
COMMUNICATION
VOLUME 30, NUMBER 1 • SPRING 2014
FOUNDER: LLOYD J. NEY, SR.
FOUNDED 1984
Inside this Issue:
Male Lumpectomy: Focal Therapy is the Future of
Prostate Cancer Treatment
Treatment Options for
Post-Prostatectomy
Incontinence
What the Heck Has Been
Going On In My World
Challenging PC
Treatment Biases –
Is Nothing Sacred?
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Life Without Prostate Cancer:
Imagine The Possibilities!
TABLE OF
CONTENTS
Bonus Book............................................................................................. 2
Conference – September 5-7, 2014........................................................... 2
Los Angeles, CA
PROSTATE
CANCER
COMMUNICATION
Published Quarterly by: PAACT, Inc.
Patient Advocates for Advanced Cancer Treatments
1143 Parmelee NW
Grand Rapids, MI 49504
President…Richard H. Profit Jr.
Editors….Richard H. Profit Jr./Molly Meyers
Staff….Molly Meyers
David Sochacki
Webmaster….Omega Systems
Male Lumpectomy: Focal Therapy is the Future of
Prostate Cancer Treatment....................................................................... 3
By Gary Onik, MD
Treatment Options for Post-Prostatectomy Incontinence........................... 7
By Gary E Leach, MD
What the Heck Has Been Going On In My World - Part 64........................... 10
By Mark A Moyad, MD, MPH
Challenging PC Treatment Biases – Is Nothing Sacred? Part 2................... 17
By Robert (Dr. Bob) Leibowitz, MD
Acknowledgements............................................................................... 22
PAACT Membership Form........................................................................ 24
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Foreword by John Blasko, MD
University of Washington, Seattle, WA
Clinical Professor - Radiation Oncology
MALE LUMPECTOMY: FOCAL THERAPY
IS THE FUTURE OF PROSTATE
CANCER TREATMENT
GARY ONIK, MD • THE ONIK PROSTATE CANCER CENTER - AVENTURA, FL
CONTACT: KAREN BARRIE, MS (847) 502-1414 OR EMAIL: [email protected]
INTRODUCTION
For both patients and doctors, current prostate cancer
management reminds me of Oliver Hardy saying to Stan
Laurel, “This is another fine mess you have gotten me into!”
Relying on radical treatments with high morbidity, we seem
to have abandoned the basic tenets of cancer therapy:
1. Find it early.
2. Stage it as accurately as possible.
3. Treat it aggressively, appropriate to its stage and tumor
aggressiveness.
We find ourselves in a paradoxical situation. Early detection
of prostate cancer has become difficult, if not impossible, due
to new guidelines against routine PSA screening. Why did
the U.S. Preventive Services Task Force, a volunteer panel of
medical professionals, rule against wide use of a simple and
effective screening tool? First, men with suspicious or rising
test results are sent for an unpleasant diagnostic procedure
(TRUS biopsy) that has been proven to miss up to 30% of
cancers. Those with negative biopsies later have repeat
biopsies, while expense (and anxiety) mount up. Second, this
protocol finds too many less aggressive cancers—and the
cure may be worse than the disease.
A dilemma between overtreatment vs. no treatment occurs
when patients diagnosed with low-to-moderate risk
cancer are counseled to defer treatment in favor of active
surveillance, a strategy for which many patients don’t have
the psychological tolerance—they worry that a time bomb
is ticking in their bodies. This worry may well be justified
by a recent UCLA study showing how prostate cancer cells
are a moving target. (1) Yet this advice is given so men can
hold off on the risks of overtreatment: urinary and sexual
side effects. So we don’t go looking for cancer because we
might find it, over treat it, and damage men’s quality of life?
Can you think of any other cancer for which early detection
is discouraged and treatment delayed? It is extremely rare to
suggest that other cancers (breast, liver, lung, kidney, liver,
etc.) can simply be monitored!
My twofold thesis addresses this dilemma by offering a safe
and effective middle ground:
A.For diagnosis, there is an alternative to TRUS biopsy that
is extraordinarily accurate, painless, and does not involve
puncturing the rectal wall. It is the 3D Transperineal Prostate
Mapping Biopsy (3D-PMB), which is more disease-specific
for low, moderate and high-risk cancers than MRI-guided
targeted biopsies. It improves prostate cancer management
decisions by up to 70% because it allows matching the
treatment to the disease, and it provides specific localization
for precise targeting. In short, it meets the first and second
tenets of cancer therapy.
B. For treatment, there is an effective FDA-approved minimally
invasive procedure that satisfies the third tenet of cancer
therapy, to the major benefit of the patient.
THE MALE LUMPECTOMY
This article describes our latest results with both 3D-PMB
and focal cryotherapy (cryoablation, or simply cryo, meaning
lethal freeze). Our data validates the advantages of what I
first termed the Male Lumpectomy.
I now have long term results (average follow up of 10 years)
with focal cryotherapy for prostate cancer or the Male
Lumpectomy. I first presented this idea in a 2002 paper
(2) demonstrating that we could effectively locate and
target a prostate tumor without having to destroy, remove
or irradiate the whole gland. By isolating and treating just
the tumor and a surrounding safety margin, we generate
competitive (actually better) efficacy in controlling cancer
while preserving healthy tissue to markedly lower morbidity
(side effects).
That paper started the ball rolling. Focal prostate cancer
therapy is now carried out in some manner in major U.S.
cancer centers, including MD Anderson, Johns Hopkins,
Sloan Kettering, Duke and NYU to name a few. Textbooks
cover the subject and annual medical meetings on this topic
are convened. The results are consistent: good cancer control,
yet low side effect risks.
My own study data offers compelling evidence that mapping
biopsy and focal cryo provide a combined clinical approach
www.paactusa.org • Spring 2014 / Prostate Cancer Communication 3
that completely changes the current paradigm, meeting the
highest cancer treatment standards, and bringing it fully in
line with the best therapies for local treatment of any other
tumor. Additionally, this approach greatly reduces the high
economic costs of conventional prostate cancer treatments
(robotic prostatectomy and radiation therapy), as well as
the long term personal quality of life costs (with their own
associated management dollars).
MATERIALS AND METHODS
In our practice, we stage patients for focal therapy using
3D Transperineal Prostate Mapping Biopsy (3D-PMB).
Transrectal ultrasound (TRUS) guided biopsy is not enough
to guide focal therapy. 3D-PMB is carried out under general
anesthesia (so it’s painless). Unlike a transrectal biopsy, which
takes prostate samples through the rectal wall, 3D-PMB is
done through the perineum (the skin between the scrotum
and rectum). A grid, like that used in brachytherapy, is
placed against the skin, and ultrasound guides the position
of needles into the gland. Note that while ultrasound cannot
distinguish important differences in normal and cancerous
tissue, it clearly shows the placement of biopsy needles.
Tissue samples taken throughout the gland are separately
marked with the grid coordinates so their precise location is
identified in the pathology report. This is what gives a threedimensional or holographic map of any cancers, even very
small ones that might be found. We are able to take far more
samples than the 10-12 commonly taken in a TRUS biopsy.
3D-PMB also has the advantage of more accurate Gleason
scores since there’s little risk of missing a tumor core where
the more dangerous cells tend to be.
A study we published in the most prestigious cancer journal
in the world (Journal of Clinical Oncology) compared the
results of TRUS biopsy vs. 3D-PMB in over 180 patients (3).
What we found was sobering. Compared to TRUS biopsy,
3D-PMB found 50% more cancer on the opposite side of
the gland. It also raised the Gleason score in approximately
25% of patients. Additionally, a 3D-PMB is safer than TRUS
biopsy because it is a sterile procedure, greatly lowering
the chance for life threatening sepsis (infection with colon
bacteria) and debilitating prostatitis that are significant
risks in TRUS biopsy. Identifying the exact location of each
specimen allows exact treatment targeting of the tumor,
including its location, size and shape.
Some clinicians are using MRI guided biopsies to guide
focal therapy. Studies comparing MRI to mapping biopsy or
prostatectomy specimens show that it misses 25% of significant
cancers (4) and is only 28% specific, meaning that 72% of the
time what it reads as cancer is not (5). While I support advanced
multiparametric MRI of the prostate as an adjunct resource,
only 3D-PMB can give the thorough tissue map necessary for
long term cancer control as demonstrated by my data.
4
Prostate Cancer Communication / Spring 2014 • www.paactusa.org
What about the concern that biopsies spread cancer? There
is absolutely no credible clinical evidence that this happens.
Why is this important? Fears of “track seeding” have been
sadly overplayed by a handful of doctors who feed patients’
wishful thinking that prostate cancer can be clinically
diagnosed and staged by imaging alone. In fact, MRI or color
Doppler is not specific enough to make an accurate diagnosis
of prostate cancer, meaning it often OVER estimates less
aggressive cancer, and is not sensitive enough in identifying
very small but significant cancers. Anyone who tells you,
based solely on imaging, that you have cancer is doing you
a great disservice—especially if they proceed to treat you.
It is my conviction that any physician who treats based on
imaging and/or rising PSA without biopsy confirmation
is committing the grossest kind of malpractice. In the last
month I encountered two patients who had been offered
radiation without biopsy confirmation of cancer. I was
appalled, as this violates the universal medical ethic, “Above
all do no harm” (primum non nocere).
In our practice, we originally theorized that perhaps 25-30%
of prostate cancer cases would be amenable to focal therapy.
Our experience, confirmed by another study (6), showed that
as many as 94% of patients qualify for a focal approach. In
other words, focal therapy is more than a “niche” treatment—
many more men may benefit, especially when their disease is
accurately diagnosed and staged, and when the treatment is
done by an expert.
Once you have located the tumor there are a number of ways
to kill the cancer. We mainly use cryotherapy (cryoablation
or simply “cryo”) to carry out the focal therapy. Cryo is
the only ablation modality that has Level One evidence
of superiority over beam radiation in eradicating cancer
(compared in a randomized study) (7). Another excellent
reason to use cryo comes from evidence of a specific tumor
immunologic effect when a cancer is frozen. This effect has
been shown in animal models to prevent metastatic disease
and to cause regression of distant prostate cancer metastases
(spread) in patients. Our cancer control results with medium
and high risk patients are so much better than reported data
with radical prostatectomy or radiation that an immunologic
explanation for these results must be considered. Heat-based
therapies such as laser and HIFU denature (destroy beyond
recognition) tumor proteins (antigens). It is these antigens on
the surface of cells that scatter into the body. Since they are
not intact cells they cannot spread or cause cancer, but they
are helpful because they appear to trigger this immunologic
effect (8, 9). I predict it will take at least a decade to see if heatbased ablation gets the same immunologic results. Personally,
I don’t want to deprive my patients of this potential benefit,
particularly when there is no advantage I can see, as yet, to
other ways of killing the tumor.
FOCAL CRYO RESULTS
In our practice, we now have clinical data on a total of 70
patients who underwent focal cryo. All have at least 8 years
follow-up (ranging from 8 to 18 years with a mean follow
up of 10.1 years). 41 patients were Gleason 6 or less, 24
were Gleason 7 (6 patients 4+3, 18 patients 3+4) and 5 were
Gleason 8 or greater. 15 patients had a PSA of 10 or greater.
We stratified the 70 patients using the D’Amico system. Thus,
29 patients were low risk, 32 medium risk, and 9 high risk.
TABLE 1: PATIENT DEMOGRAPHICS
Patients
Follow-up
70
8-18 years
Mean 10.1 years
D’Amico Risk level
Low
29
Medium
32
High
9
Gleason score
Gleason 6 or less
41
Gleason 7
24
Gleason 8 or greater
5
Stage
T1c
56
T2a
6
T2b
3
T2c
4
T4
1
PSA level at DX
less than 10
54
10-20
13
greater than 20
2
Table 1. Risk stratification of patients treated with focal prostate
cryoablation (N = 70)
Overall actuarial survival was 66/70 (94%), meaning 4
patients died from other causes. Disease specific survival
was 64/64(100%), meaning no patients died from prostate
cancer. This is a rather remarkable statistic given that the
majority of patients in this series (41) were medium to high
risk. It certainly illustrates that patients who are appropriate
candidates for focal therapy are not taking a greater risk of
death in choosing this avenue.
Overall Biochemical Disease Free Survival (BDFS, meaning
no rise in PSA) was 89% (62/70). When broken down by risk
level, BDFS for low risk patients was 90% (26/29), for medium
risk patients 88% (28/32) and for high risk patients 89% (8/9).
These again are rather remarkable results. For comparison, a
2012 article by Ginsburg, et al., looking at results of robotic
radical prostatectomy with over 1100 patients had an overall
BDSF of 72% at 5 years (10). See Table 2.
TABLE 2: RESULTS
Overall actuarial survival N=70
66/70 (94%)
Disease specific survival N=70
70/70В (100%)
Biochemical Disease Free Survival
62/70 (89%)
BDFS High Risk (D’Amico)
8/9В (89%)
BDFS Med Risk (D’Amico)
28/32 (88%)
BDFS Low Risk (D’Amico)
26/29 (90%)
Bilateral Multi focal
19/20 (95%)
Local recurrenceВ N=10
9/10 (90%)
ContinentВ after primary procedure
70/70 (100%)
Retained potency
48/60В (80%)
Table 2. Survival and recurrence rates for focal prostate
cryoablation (N = 70)
In my experience in a tertiary referral practice, having
interviewed patients who have already seen surgeons, it is
unusual to encounter a patient who has had explained to him
what a “positive margin” is. For those who are unclear, after
the gland is removed, the cut margins of the gland are stained
and microscopically examined for tumor. If tumor is found at
the cut margin the implication is that there is residual cancer
left in the patient. This is called a positive margin. It leads
to a high rate of disease progression. In Ginsburg’s study
positive margins occurred in 27.3% of patients, which the
authors describe as in keeping with national statistics. Our
results, with selective tumor destruction while preserving
healthy, functional prostate tissue, hold great promise for
patients who might otherwise undergo surgery, with its risks
of short and long term urinary and sexual side effects, only to
experience a rising PSA within years of the treatment.
Why all risk levels of patients would have the same cancer
control results, might have two possible explanations:
1.Focal cryo has an ability to treat extracapsular disease.
Patients at high risk for positive margins at prostatectomy
have a better chance of local control with ablative therapy.
This was very well illustrated by one of our patients who had
a T4 lesion already invading the bladder, a PSA of 200 and a
Gleason score of 10. He is now 8 years out from his cryo with
no evidence for recurrence. We also have used a localized
removal of urethral tissue in some patients who had tumor
next to the urethra, when we were afraid that the urethral
warmer might prevent a completely destructive freeze at that
site.
2. A cryoimmunological response must also be considered for
these remarkable results in medium and high risk patients.
Based on the human and animal data, it’s likely that in some
patients there is exposure of tumor antigens at the time of the
www.paactusa.org • Spring 2014 / Prostate Cancer Communication 5
procedure that acts as an in vivo cancer vaccine, preventing
later metastasis from occurring.
A WORD ABOUT RECURRENCE
Choosing radiation or RP as a first or primary treatment
limits future options. Neither has a good fallback position
should local disease recur. Hormone ablation is not curative,
and the side effects are unpleasant. However, when focal cryo
patients are retreated they do extremely well. The ability to
retreat patients with local recurrences by repeat freezing, or
even RP or radiation, means that our patients have less chance
of untreated local residual cancer that can later spread.
In our series, 10% of patients (7/70) were retreated with
cryo to the opposite side of the original procedure. (In other
words, a second cancer later occurred in previously biopsynegative and therefore untreated tissue.) All 7 (100%) are
biochemical disease free (BDF). Two patients with local
recurrence underwent radiation and both are BDF. One
patient underwent RP and radiation and is now on ADT
(hormone ablation). In total, 14% of patients (10/70) had
a local recurrence that required re-treatment, and 90% of
those 10 patients (9/10) remain BDF.
Bilateral disease (cancer on both sides of the gland at initial
treatment) was not a barrier to successful focal therapy. In
our series, 28.5% (20/70) of patients had bilateral multifocal
disease (more than one tumor location) that required
bilateral cryo. Of those, 95% (19/20) were BDF.
FOCAL CRYO SIDE EFFECTS (MORBIDITY)
The hope for low morbidity associated with focal therapy has
been confirmed by our results. All patients were continent
(with no pads) immediately after the first procedure (100%).
One recurrent patient converted to a second whole gland
freeze, resulting in mild stress incontinence requiring pads
while playing golf. Other authors confirm these continence
results (11).
As to potency, focal therapy did extremely well. 58/70
patients were potent preoperatively (pretreatment baseline
function).В 54/58 (94%) were potent postoperatively with or
without the use of oral agents, to their satisfaction,В within
6 months. However, 11 patients were ultimately rendered
impotent by additional treatment (7 by additional cryo, 4 by
a combination of ADT, radiation or radical prostatectomy).
Interestingly, 4/12 preoperatively impotent patients were
potent after the procedure. This was due to the immediate
potency rehab protocol that we provide, if needed. 43/58
patients (74%) therefore ultimately retained potency. Again,
these results are consistent with other focal therapy series.
No other complications were noted. Blood loss was virtually
zero. No rectal fistulas were seen and no patient needed a
6
Prostate Cancer Communication / Spring 2014 • www.paactusa.org
further procedure for urinary obstruction.
CONCLUSIONS
The long term results of focal cryoablation, within the
limitations of our data, is significantly superior to traditional
RP and radiation. Unanticipated is that patients at high risk
for recurrence have a much higher disease free survival than
that reported with robotic RP and with better quality of life.
Repeat treatmentВ for localized recurrence does not appear to
negatively impact patient disease specific or BDF survival,
perhaps accounts for improved results in high and medium
risk patients. Patients treated with bilateral multifocal disease
appear to do as well as those with unilateral tumors. Most
striking, all grades and PSA levels appear to have excellent
results compared to other therapies. When including all risk
levels of disease and bilateral disease, the overwhelming
majority of patients would be eligible for this approach
when appropriately diagnosed, staged, and treated by an
experienced cryosurgeon.
The Male Lumpectomy achieves these results with minimal
morbidity in terms of incontinence and potency. The
safety and long term efficacy of focal cryoablation is now
established, though this is not to say that further study is
not needed. Enough evidence is available, however, that I
would have no qualms about offering this option to qualified
patients. Future investigators now have the data to have a
comfort level to conduct comparative Level One evidence
studies between focal therapy, robotic RP and the various
forms of radiation.
This data also sets the bar high for focal therapy. When
developing this approach, we tried to optimize every step
of the procedure to give us the theoretically best outcomes
possible with our current knowledge. All of the important
aspects of our methods for selecting and performing focal
therapy are supported by Level One data as being the best
way to carry out this mission (3D-PMB for diagnosis and
staging, cryo for the ablation). Since we are dealing with
peoples’ lives, anyone carrying out focal therapy should
adhere to the principles we have outlined in selecting and
performing the procedure. Based on my experience there
will be a plethora of focal therapy methods being touted in
the near future. It’s going to take other investigators another
ten years to figure out if their method can produce the same
results. As a patient, you will be challenged to sort out proven
treatments with a published, peer-reviewed track record vs.
“the latest” innovations without long-term results.
We have been going down the same path with prostate cancer
for so long. Despite the best efforts of urologic surgeons and
radiation therapists to improve the results of their traditional
treatments, little progress has been made in improving
survival and lowering complications. Focal therapy gives us a
new, exciting and hope-filled alternative road to take. It will
be the responsibility of the medical community to thoroughly
compare focal therapy as we have outlined it, honestly and
fairly, with traditional therapies. If this is accomplished I
am confident that we will have embarked on a new era in
prostate cancer management.
REFERENCES
(1) Stoyanova T, Cooper A, Drake J et al. Prostate cancer originating in basal cells
progresses to adenocarcinoma propagated by luminal-like cells. Proceedings
of the National Academy of Sciences, published online Dec. 2013. atВ http://
www.pnas.org/content/early/2013/11/25/1320565110.full.pdf+html
(2) Onik GM, Narayan P, Vaughn D, et al. Nerve sparing cryosurgery for the
treatment of primary prostate cancer: a new approach to preserving potency.
Urology. 2002 Jul;60(1):109-14.
(3) Onik, G.В Miessau M,В Bostwick DGВ Three-dimensional prostate mapping
biopsy has a potentially significant impact on prostate cancer management.В J
Clin Oncol.В 2009 Sep 10;27(26):4321-6. 2009 Aug 3.
(4)DelongchampsВ et al.В Multiparametric MRI is helpful to predict tumor
focality, stage, and size in patients diagnosed with unilateral low-risk prostate
cancer. Prostate Cancer and Prostatic Diseases (2011) 14, i232–237.
(5)Abd-Alazeez1 A, Kirkham HU, Ahmed M et al. Performance of
multiparametric MRI in men at risk of prostate cancer before the first biopsy:
a paired validating cohort study using template prostate mapping biopsies as
the reference standard. Prostate Cancer and Prostatic Disease (2013), 1–7.
(6)Singh PB,В Anele C,В Dalton E,В et al. Prostate cancerВ tumour features on
templateВ prostate-mapping biopsies: Implications for focalВ therapy. Eur
Urol.В 2013 Oct 6. http://www.ncbi.nlm.nih.gov/pubmed/?term=singh+anel
e+prostate
(7) Donnelly BJ, Saliken JC, Brasher, PMA et al. A randomized trial of external
beam radiotherapy versus cryoablation in patients with localized prostate
cancer. Cancer 2010;116:323-330.
(8) Ablin et al.В Cryobiology,В 8:271, 1971.
(9) Waitzl R, Solomon S, Petre E et al. Potent Induction of Tumor Immunity by
Combining Tumor Cryoablation with Anti–CTLA-4 Therapy. Cancer Res;
72(2) January 15, 2012.
(10)Ginzburg S, Nevers T, Staff I et al. Prostate cancer biochemical recurrence
rates after robotic-assisted laparoscopic radical prostatectomy. JSLS
2012;16:443-50.
(11)Bahn E, Abreu AL, Gill I et al. Focal cryotherapy for clinically unilateral, lowintermediate risk prostate cancer in 73 men with a median follow-up of 3.7
years. Eur J Urol 2012 July;62(1)55-63.
TREATMENT OPTIONS FOR POSTPROSTATECTOMY INCONTINENCE
GARY E LEACH, MD • DIRECTOR - TOWER UROLOGY INSTITUTE FOR CONTINENCE
TOWER UROLOGY - LOS ANGELES, CA
Loss of bladder control (urinary incontinence) after prostate
surgery is a devastating complication, which has 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 for more than 3-6 months after radical prostatectomy,
appropriate bladder testing (called urodynamics) is critical
to evaluate the function of the bladder and sphincter
(valve) muscle to determine the exact cause of the postprostatectomy incontinence (ppi). This urodynamic testing
is performed in the office and takes about 20 minutes. The
test involves filling the bladder through a special catheter
inserted in the penis, 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 research has defined three main causes of ppi based upon
urodynamic findings:
1. High pressure (with �spasms’ of the bladder) developing in the
bladder as the bladder fills (50% of men with ppi). It is possible
that these bladder spasms are related to nerve damage that may
have occurred as a result of the prostatectomy. 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. This high pressure bladder dysfunction can also occur
following pelvic radiation therapy. Normally, when the bladder
fills, the bladder pressure remains low without any spasms.
2. 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.
www.paactusa.org • Spring 2014 / Prostate Cancer Communication 7
3. A combination of bladder spams 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/Pelvic Floor Training may be a treatment choice
in men who are incontinent and desire treatment early after
radical prostatectomy (especially 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 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 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.
When the main cause of the incontinence 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 and improvement in bladder spasms. Medicines
to relax the bladder (generally known as anticholinergics)
include: Enablex, Vesicare, Ditropan XL, Detrol LA, the
oxytrol patch, oxybutynin 3% gel 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. There is also a new type of oral
medication, called Myrbetriq, which helps relax the bladder
by stimulating different receptors in the bladder wall. Thus,
Myrbetriq does not cause the typical dry mouth and constipation
side effects so common with all the other medications that have
been used for years. However, 10% of those who take Mybetriq
may experience some increase in blood pressure. Many men
that have not been able to tolerate the traditional medications
used in the past, benefit from this new medication.
When the oral medications fail to control the high bladder
pressures, the Interstim “bladder pacemaker” device can be
an excellent treatment option. This bladder pacemaker device
can be tested in the office with promptly 70% of the patient’s
responding during the seven-day test. If there is a beneficial
response to the seven-day test, implantation of the permanent
bladder pacemaker can be considered. This procedure is
performed as an outpatient under local anesthesia.
Another option for controlling high bladder pressures, when the
8
Prostate Cancer Communication / Spring 2014 • www.paactusa.org
oral medications are not successful, is Botox injection into the
bladder. The Botox is injected in the office setting through the
cystoscope with approximately a 50% success rate. The Botox
usually has a maximum duration of benefit in the range of six
months requiring repeat injection on a regular basis. There is also
a 5% risk of urinary retention associated with Botox injection. If
urinary retention should occur, the patient may be required to
perform self-catheterization 3 to 4 times per day until the effect
of the Botox diminishes. Both the Interstim bladder pacemaker
device and Botox injection are now covered by Medicare.
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 anticholinergic drugs, Interstim
or Botox) 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 an office
test with placement of wires next to the nerves that control the
bladder under local anesthesia. For seven days, the patient wears
a battery in the belt which sends an electrical signal to the nerves
that control the bladder. The goal of this stimulation is to relax
the bladder during filling. This office test of the Interstim device
is approximately 70% successful. If the patient responds well to
the office test, the permanent Interstim device is implanted as an
outpatient in the hospital under local anesthesia. This procedure
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.
Next, the implantation of an internal �pacemaker’ generator
that is attached to the stimulation electrode is performed and
then programmed through the skin (Figure 1b). The generator
is very similar to a heart pacemaker with a battery that usually
lasts 8-10 years. Overall approximately 70% of patients respond
to the office trial of test stimulation. When we proceed with
the permanent 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 for 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 30 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 10 years after implantation of the device. 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 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 over-night 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 (see figure 3). In the author’s experience, the most
effective material used for the sling is a specially prepared
synthetic patch which compresses the urethra. 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. Approximately 30% of men
are completely dry, 40% are significantly improved, and 30% are
considered failures. If the male sling is not 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 Tower website:
towerincontinence.com or towerurology.com
Also, Dr.
Leach can be reached by e-mail: [email protected].
References:
1. G Leach, B Trockman, and A Wong, et al.: Post-prostatectomy incontinence:
urodynamic findings and treatment outcomes. J. Urology 155:1256,1996.
2. 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.
www.paactusa.org • Spring 2014 / Prostate Cancer Communication 9
WHAT THE HECK HAS BEEN
GOING ON IN MY WORLD-
PART 64!
B Y M A R K A . M O YA D , M D , M P H , U N I V E R S I T Y O F M I C H I G A N
Note: A total of 64 times in a row (and for 15+ years!) I have written and
volunteered for this newsletter, and I have yet to receive any personal
financial compensation or personalized classic timeless gifts such as: a device
that immediately turns OFF the show “Duck Dynasty” when it comes on the
television set (I don’t get it…crazy Grandpa says something crazy and people
lose their mind like they expected him to be able to split the atom one day
or cure cancer or solve the world peace issue just because he can produce a
great duck calling device), an official PAACT snow shovel, an official PAACT
space heater and blanket, official PAACT salt pellets for the icy driveway, a
first class ticket to Kona, Hawaii BECAUSE I CAN’T TAKE THIS SNOW
AND COLD ANYMORE, and in fact ”I am mad as hell and I am not going
to take this anymore!” (From the Movie “Network” Circa 1976 - it won 4
academy awards).
PS. If Bing Crosby would have recorded a follow-up song to White Christmas
called “I am dreaming of a Green Dry Spring” he would have made billions
of dollars this year (well - actually his estate would have made billions, but
you get my point)!
PPS. Oh and to my parents who are living in Florida right now…I get it! No
more! You don’t need to call me 24 hours a day, 7 days a week and instead of
saying “hello” on my message machine you start every message with “it was
80 degrees today!” and then you get to the “we love you” part. If you loved
me you would cease and desist telling me about the weather in your part of
the world or acting like you are working for the weather channel in Sarasota,
Florida. I am your fragile son and without any ultraviolet light the next best
thing is to NOT remind me of the importance of regular ultraviolet light…oh
and I love you too mom and dad #needsnowgoneasap.
PSEUDO BREAKING NEWS (note: this is not really breaking
news but I thought it would get your attention - hey network
news stations do this all the time and announce “breaking
news” and in reality it is just Miley Cyrus stubbing her toe
or something like that)… I am asked about fruit juice all the
time, so let me put it to rest (but the next story on vitamin E
is really breaking news!).
270) Fruit juice and many exotic and pricey juices are the
new Coca-Cola or Pepsi in the Moyad World?
(Reference: Coca-Cola Web Site and Fruit Juice Web Sites)
BOTTOM LINE
I received many questions on this and let me try and give
my quick and simple opinion - I believe most fruit juices
are simply the same as drinking a sugary cola or worse. For
example, 1 can of Coca Cola contains 140 calories and 39
grams of sugar, and 12 ounces (1 can) of apple juice has 180
calories and 42 grams of sugar!!!! WOW!!!! In other words,
in many situations I think fruit juice is the same or worse
than sugary soda!
10
Prostate Cancer Communication / Spring 2014 • www.paactusa.org
WHAT ELSE DO I NEED TO KNOW?
Nothing else! Just in case you missed it lets review:
COCA-COLA 8 OUNCES = 26 GRAMS OF SUGAR AND 95 CALORIES
APPLE JUICE 8 OUNCES = 28 GRAMS OF SUGAR AND 120 CALORIES!
GRAPE JUICE 8 OUNCES = 36 GRAMS OF SUGAR AND 140 CALORIES
ORANGE JUICE 8 OUNCES = 22 GRAMS OF SUGAR AND 110 CALORIES
POMEGRANATE JUICE = 31 GRAMS OF SUGAR AND 150 CALORIES
ANY QUESTIONS? Yikes!!! Oh, but Dr. Moyad those fruit
juices have some vitamins and minerals in them so that is
good, right? Look, I had a large pepperoni pizza with a lot of
cheese last night and beer and that had vitamins and minerals
in it too! The calorie and sugar counts on these juices simply
outweigh any benefits, so personally I stay about as far away
from them as an Ohio State Football Class Reunion party (I
am talking about the Coach Cooper years when we used to
beat Ohio State all the time)!
REAL BREAKING NEWS
271) Vitamin E supplements at 2000 IU per day might
slow functional decline in patients with Alzheimer
disease and reduce caregiver time by up to 2 hours per
day! And, it was about as safe as a placebo. So, why the
heck are you mentioning this in the PAACT newsletter for
prostate cancer when we already know this supplement
can increase the risk of prostate cancer?! Moyad is losing
it folks!
(Reference: Dysken MW et al. JAMA 2014;311:33-44)
BOTTOM LINE
Vitamin E dietary supplements can slow functional decline
in patients with mild to moderate Alzheimer disease. Dietary
supplement recommendations should be individualized
based on the disease and situation (like Rx drugs) and should
not be generalized in terms of recommendations.
WHAT ELSE DO I NEED TO KNOW?
Vitamin E and memantine (NamendaВ®) have demonstrated
some benefit in moderately severe Alzheimer disease (AD),
but there is a lack of evidence in mild to moderate AD.
Researchers initiated a major clinical trial to determine if
vitamin E at 2000 IU/day, memantine, both, or placebo
slows progression of mild to moderate AD in patients
already utilizing an acetylcholinesterase inhibitor (AChEI or
conventional treatment). This was a double-blind, placebocontrolled, parallel-group, randomized clinical trial with 613
patients with mild to moderate AD at 14 Veterans Affairs
medical centers.
there are exceptions such as Alzheimer disease. Yet, what
if someone was diagnosed with prostate cancer and has
Alzheimer disease. This would be a decision that you and
the doctor you trust the most must make, but it should be an
option for any Alzheimer patient, so ask your doctor ASAP.
After an average follow-up of 2.27 years, participants
ingesting vitamin E had a delay in clinical progression of
approximately 6.2 months. Caregiver time was reduced by
2 hours per day in the vitamin E group. Safety and all-cause
mortality were not different among groups overall. Thus,
patients with mild to moderate AD utilizing 2000 IU of
vitamin E per day compared to placebo resulted in reduced
functional decline and caregiver burden and it was overall
very safe. It did not delay cognitive or memory deterioration
but it did temporarily protect their ability to perform daily
activities like feeding themselves and putting on clothes. This
is a big deal folks, especially since it costs pennies a day.
This clinical trial represents remarkably good news not only
for Alzheimer patients, but the dietary supplement industry
and I find it ironic that just 1 week before the publication of
this groundbreaking article there were “experts” in multiple
reputable journals arguing, without any rebuttal, that
supplements, in general, are a waste of money. Well, let me
give you some advice, similar to dealing with people, religion,
race, ethnicity, political parties, medications etc., please do
not generalize because it only makes one look naГЇve, and
ill informed. Vitamin E has a critical role in a few areas of
medicine, and just because it is not prostate friendly does not
mean it should never be used! This is a classic point I try
to teach students, consumers, and health care professionals
every week and some get it and some do not, but hopefully
after reading this part of the newsletter it will shed high
beam lights on how to deal with any future pill that someone
recommends or not. So, when you read an article that stating
that fish oil might increase the risk of prostate cancer, this
does not mean it is true, nor does it mean that that fish oil
would have no place in medicine. Every supplement at a
certain dosage is dangerous, and not needed by many, but at
the same time it might be needed by other individuals. Look
at aspirin, depending on your situation you might need a high
daily dosage, moderate daily dosage or even a baby aspirin or
you might need to stay away from it entirely because the risk
of ulcers or internal bleeding exceeds the benefit. Geez, this
was a really serious opening to my column! However, this
was a serious topic that required little to no levity.
Hmmmm…. “Supplements don’t work!?” “Don’t waste your
money!” “Vitamin E increases the risk of prostate cancer so do
not use it for any other medical condition.” These are just some
of the ridiculous, silly, or inane generalizations or comments
I hear from “experts” on a regular basis. I have tried for
decades to convince the public and health care professionals
that like prescription drugs dietary supplements can be
immensely helpful, could have no impact, or be downright
dangerous depending on the specific medical condition. We
need to eliminate the perceived and realistic bias by some
in the medical profession that appear to just want to answer
the supplements question with a generalized and sweeping
“yes” they work or “no” they don’t work. Supplements are
really no different than over the counter or prescription
drugs that need to be individualized. Generalization in the
supplement world, like in life, is a mistake you should never
make especially after this clinical trial (the equivalent of a
phase 3 by the way, an incredibly well done trial - actually
outstanding). If this supplement were a drug it would have a
shot at FDA approval after these results.
Vitamin E supplements significantly slowed functional
decline by 6 months (similar to FDA approved drugs) and
reduced caregiver time by approximately 2 hours per day,
which could be the difference between patient independence
and dependence! These are, I believe, striking results for a
dietary supplement that only costs pennies a day! In other
words, vitamin E now arguably becomes a potential major
player for the treatment of individuals with Alzheimer
disease if this is true, because let’s face the facts here, there
are no great treatments for Alzheimer disease! Yet, it does
not change the fact that it should not be used, for the most
part, in those concerned about prostate cancer. In other
words, the risk exceeds the benefit for most individuals, but
272) Mercury dental fillings and fish with some mercury
are bad for you and can encourage many diseases?!
Hmm and did I tell you that Big Foot and I were best
friends in high school and UFOs land in my backyard
every Saturday afternoon in Fall so the Aliens can walk
to the Michigan Football games from my house without
paying the high price for parking?!
(Reference: Nicolae A, et al. BMC Oral Health 2013;13:44)
BOTTOM LINE
The benefits of eating fish outweigh the negatives and the
benefits of mercury fillings outweigh negatives.
WHAT ELSE DO I NEED TO KNOW?
I am concerned, in rare cases, about over exposure to
mercury but the problem is the lack of objective reporting
by some “experts.” For example, in one of the largest studies
ever conducted on mercury exposure from fish (Mozaffarian
www.paactusa.org • Spring 2014 / Prostate Cancer Communication 11
D, et al. N Engl J Med 2011;364:1116-1125) that included
over 170,000 men and women, researchers found a LOWER
risk of cardiovascular disease in those with higher mercury
exposure. In other words, overall, the benefits of eating
fish outweighed the negatives (the higher exposure to
mercury). However, I believe there are some cardiovascular
concerns with higher mercury exposure but overall fish with
higher concentrations of omega-3 fatty acids (anchovies,
herring, mackerel, salmon, sardines, trout, GREAT LAKES
WHITEFISH…) tend to be less concerning.
One of the better studies ever conducted on mercury in teeth
was completed recently in Canada and found that dental
amalgams were NOT a hazardous source of mercury in
humans. These researchers looked at the average mercury
concentration in the population and the number of amalgam
surfaces. Overall, mercury levels were well below those
associated with health risks. Still, this study just adds to the
majority of studies conducted in the U.S. and Europe that have
NOT FOUND any issues with dental amalgam. Mercury levels
considered to be safe in the urine (if you are really curious) are
5 ug Hg/g Cr (expressed as ug Hg per gram creatinine) or 7
ug Hg/L (expressed ug Hg per liter of urine). Keep in mindjust because a blood test or urine test shows you have higher
mercury levels should not discourage you and should not make
you want to take out mercury fillings. I have several mercury
fillings and I have never had a mercury urine test because I have
never been concerned about it and I would rather spend my
time wondering why people stick up their middle finger at me
and yell when I drive the speed limit.
DMSA (dimercaptosuccinic acid) has been used to reduce
lead intoxication when specific criteria are met (check with
your doctor) and it has been used in some rare cases for other
metal exposures such as mercury. I have received many
letters about getting DMSA from an alternative medical
practitioner, if you have cancer, to reduce toxins and slow
the growth of the cancer. I don’t think this is a good idea.
DMSA works by binding to these metals and forming a metal
complex, which is then excreted in the urine. However,
DMSA is also controversial because it may be over hyped and
used to promote large benefits in a variety of situations like
those with Autism Spectrum Disorders and cancer. It has a
purpose for those over exposed to lead but otherwise should
not be given carelessly. Part of what DMSA is touted to do is
potentially raise glutathione levels (an antioxidant produced
by the human body), but this can also be done through heart
healthy lifestyle changes.
273) Almost everyone is actually deficient or does not get
enough of a specific nutrient! No, it’s not just potassium
as I mentioned in the last issue (FY I- recommended daily
allowance, RDA, for potassium is 4700 mg per day, but
12
Prostate Cancer Communication / Spring 2014 • www.paactusa.org
this mystery nutrient has an RDA of 420 mg per day or
less!). So, what is this other nutrient?
(Reference: Del Gobbo LC, et al. Am J Clin Nutr 2013;98:160-173.)
BOTTOM LINE
Magnesium, especially from food sources should be your new
best friend! Remember in the last issue that potassium has
simply become the forgotten nutrient in most individuals and
in those taking Zytiga! The recommended daily allowance
(RDA) is very high or 4700 mg per day. I have never met
a single person that knows this! However, low magnesium
levels are also a problem in many individuals including those
taking acid reflux medications, metformin and probably
many other drugs.
WHAT ELSE DO I NEED TO KNOW?
Low magnesium is a big, big problem for many men and
women reading this column right now. Why? Few people
realize that the recommended daily allowance (RDA) is less
than 420 mg a day for almost everyone except it is hard to get
this amount. How about taking a simple magnesium dietary
supplement? Not a bad idea but if you take too much it can
cause really soft stools (not the bean bag chair kind you have
in your living room) and diarrhea. Still, most Americans
are not getting enough potassium in their diets (mentioned
in a previous Moyad column) nor are they getting enough
magnesium. Dietary magnesium has been associated with a
lower risk of cardiovascular disease (CVD) and may prevent
a lot of health issues. Very low magnesium might increase
the risk of cardiac problems including arrhythmias.
Numerous popular drugs used by some prostate cancer patients
can reduce blood magnesium levels including metformin and
acid reflux drugs. Increasing levels of blood glucose and insulin
can reduce magnesium as well as alcohol intake. There is now
evidence that lower intakes of dietary magnesium are associated
with a greater risk of CVD and dying from CVD. Magnesium also
helps reduce the risk of constipation and kidney stones, which is
why many calcium supplements now contain some magnesium.
What is the impact of magnesium on prostate cancer? We have
no idea, but the overall health benefits are so outstanding that
everyone should know about this nutrient. The recommended
dietary allowance (RDA) of magnesium is approximately 400420 mg per day for adult men and 310-320 mg per day for adult
women. Green leafy veggies such as spinach and higher fiber
foods tend to contain more magnesium. For example, nuts such
as almonds, seeds, and beans (soybeans…) are good sources.
One of my favorite sources is avocado because it is also high
in potassium and healthy fat. Fish, brown rice, plain yogurt,
and even bananas are also high in magnesium. You can take a
magnesium supplement, but keep in mind that primarily heart
healthy foods are a good source of magnesium, so it is best to
stick with food sources.
Magnesium is a forgotten nutrient today (kind of like
the Rubik’s cube or pet rock of nutrients) because it is not
expensive and does not grab major headlines, but it has
quietly become a major player in improving health and
wellness. Similar to the Michigan football team that deserved
to beat Ohio State in football in 2013 (No, I will never live
that game down), magnesium deserves more attention and
respect! Regardless, I hope you get more magnesium in your
diet in 2014 and if you are really curious ask your doctor to
pull your magnesium blood level next time you give blood
because it will give you a good idea of how you are doing
(it is an accurate test folks)! There is preliminary research
that magnesium in drinking water and other sources might
reduce the risk of prostate cancer, but this is so preliminary
that I would assume for now that magnesium has no impact
on prostate cancer but does impact overall health. Again,
review my favorite list of magnesium foods and see how
heart healthy they are for you!
Dr. Moyad’s 5 Favorite Magnesium Sources (apart from a
banana):
1. Avocado = 50 mg per 1 cup (healthy fat, packed with
potassium and magnesium and good with pretzels and beer)
2. Spinach = 80 mg per ВЅ cup boiled (Okay throw some
butter in with it and who doesn’t love this stuff with beer and
chips)
3. Plain Yogurt = 40 mg per 8 ounces (love this stuff with
chips and beer)
4. Almonds = 80 mg per ounce (love Almonds with beer and
chicken wings)
5. Oatmeal = 1 instant packet = 35 mg. Okay, I really can’t
stand oatmeal because to me, it has no taste unless I dump
a lot of brown sugar in it or drink beer afterward and have a
pepperoni pizza.
274) Exercise may be working as well as some prescription
drugs! And testosterone replacement therapy (TRT)
might increase the risk of heart disease? What do
these stories have in common Dr. Moyad, because you
obviously put them together in the same article for a
specific reason? Right?
(Reference: Finkle WD, et al. PLoS One 2014;9:e85805. &Naci H, Ioannidis J.
BMJ 2013;347:f5577).
BOTTOM LINE
“First do no harm” is my motto….oops that actually came
from someone known as Hippocrates (bet he never was on
the Dr. Oz show)! Right now, we have to assume testosterone
replacement therapy (TRT) might increase the risk of
cardiovascular disease (CVD) even though it has not been
proven, because CVD is the number 1 cause of death in men.
It’s possible that exercise is as good as taking a prescription
drug in many cases and in the worst case scenario makes
most prescription drugs work better, even testosterone
replacement therapy (TRT), which is not a bad case scenario
folks!
WHAT ELSE DO I NEED TO KNOW?
Testosterone replacement therapy (TRT) is an option some
men choose after being treated for prostate cancer and have
no detectable signs of disease for years and have very low
testosterone (or if they simply watch enough TV and are
convinced to use it from all those commercials)! It seems
like from all those television advertisements, TRT makes
your life so wonderful. I mean you are able to get the good
looking girl, put her in your new expensive sports car and
she laughs at all your jokes while the wind whips through her
hair! What could be more wonderful than being a magnet to
the ladies and taking TRT (okay - I realize this is silly but so
are many of those commercials).
What is the real problem here? Another new piece of research
suggests that taking testosterone replacement therapy (TRT)
might increase the risk of cardiovascular disease (CVD)/
heart attacks in men with heart disease. Many health care
professionals and patients having been asking my opinion of
this situation. I respond by saying “it doesn’t matter” or “it
shouldn’t matter.” Folks look at me like I am 5 eggs short of a
dozen, 2 beers short of a six pack, 1 quarter short of a dollar,
the lights are on in my house but no one’s home or I am 2
gallons short of a full tank…MAN I COULD GIVE THESE
DUMB ANALOGIES ALL DAY! What I mean is that since
CVD is the number 1 killer of men, and over 800,000 men
and women died from this disease in the past year, including
150,000 age 65 and younger, therefore, ALL MEN with or
without diagnosed heart disease should be treated as if they
are already at high risk of CVD. If you want to go on TRT,
then all heart healthy numbers and lifestyle factors should be
heart healthy. In other words, you should be losing weight/
waist, have a normal to low cholesterol, normal blood glucose,
normal blood pressure and should be exercising daily and
eating primarily a heart healthy diet (If you aren’t doing these
heart healthy things, you SHOULD NOT be allowed to go
on TRT). I watched for decades “experts” tell women that
hormone replacement therapy (HRT) might reduce the risk
of CVD and this turned out to be as wrong as the controllers
of the Titanic thinking it could swerve around an iceberg!
In a separate, but related article, one of the most extensive
analysis ever conducted on the subject concluded that
“exercise and many drug interventions are often potentially
www.paactusa.org • Spring 2014 / Prostate Cancer Communication 13
similar in terms of their mortality benefits in the secondary
prevention of coronary heart disease, rehabilitation after
stroke, treatment of heart failure, and prevention of diabetes.”
WOW! WOW spelled backwards! In a previous column
in 2013 I mentioned that from Viagra to statin cholesterol
lowering drugs to anti-depressants, it appears that if someone
exercises regularly it makes their prescription drugs work
remarkably better! TRT would also work better with exercise,
and in some cases men would never need TRT if they lost
weight/waist and their testosterone increased naturally and
their risk of CVD also decreased. The take home Moyad
message of the day is too many men (and women) have
begun to rely on prescription drugs and supplements to solve
many of the issues exercise and other lifestyle factors could
solve. We already know exercise reduces the side effects of
prostate cancer treatment, reduces fatigue (especially weight
bearing exercise) and might even reduce the risk of prostate
cancer recurrence. All of this new and old exercise research
is nothing short of miraculous…kind of like when Michigan
Basketball made it to the final four last year! However, they
still should have beat Louisville but the referees cheated
and called a foul at the end of the game on our best player
who actually didn’t foul the Louisville player (Man - I need
therapy).
275) What is the latest update with all this multivitamin
research and cancer, heart disease, cataracts, Alzheimer
disease, etc.???
(Reference: Grodstein F, et al. Ann Intern Med 2013;159:806-814, Gaziano
JM, et al. JAMA 2012;308:1871-1880., Christen WG, et al. Ophthalmology
2014;121:525-534)
BOTTOM LINE
Should I still take a daily multivitamin? What do you take?
Do you still take Centrum Silver or a Centrum Kids? What
do you eat? Why did you wear that jacket? When are you
going to cure prostate cancer? I get this question about a
1000 times a week and the answer is “yes” when it comes to
the very first question about multivitamins, because it may
reduce the risk of cancer and cataracts (the 2 big Cs)and it
also might correct some minor nutrient deficiencies. Keep
in mind that Centrum Silver® (or a children’s multivitamin)
is one of the cheapest multivitamins in America and has the
most evidence. Also, taking more than 1 pill a day is not
needed. The research suggests that even if you eat really well
including 7 servings or more of fruits and veggies, you might
still benefit from taking a multivitamin daily! How groovy
is that!
WHAT ELSE DO I NEED TO KNOW?
Why is the multivitamin the real piГ±ata of the pill world right
now? Bone headed “experts” are taking a whack at it daily!
Come on and step right up-take your best shot! Wack! Wack!
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Prostate Cancer Communication / Spring 2014 • www.paactusa.org
One medical journal that I refuse to call out and identify
(Annals of Internal Medicine) not only published the recent
research that showed Centrum Silver does not impact
cognition, but also in the same issue on Dec 23, 2013 allowed
an editorial to be published without ANY rebuttal that was
scathing and unusually candid about how multivitamins are
simply worthless (“stop wasting money…”)! Wow! That really
wasn’t nice (what a bunch of journalistic bullies)! However,
let me put this into perspective for you without trying to
be too dramatic; if you really thought taking a Centrum
daily would impact cognitive function better than placebo
within 10 years in incredibly healthy older doctors whose
average BMI is 25, less than 4% are smokers, less than 9%
are diabetics and most of whom are doing vigorous exercise
weekly and eating 5 servings of fruits and veggies daily, then
I have swamp land I want to sell you in Ann Arbor, Michigan
where there is certain to be unlimited gold and oil embedded
in it!
It is absurd to think this pill could prevent Alzheimer’s and
most other diseases in perfectly healthy individuals after just
11 years. However, what was truly surprising is that this is the
same clinical trial that found a significant modest reduction
in the risk of cancer in those with and without a personal
history of cancer when taking this multivitamin compared
to placebo, and this was one of the primary endpoints of
the study. This is also the same study that found a modest
reduction in the risk of the most common type of cataracts
and cataract surgery when taking a multivitamin, and there
is adequate research to suggest it could correct some minor
nutritional deficiencies (vitamin D, B12, B6, etc…). This was
also the study that showed it had no impact on heart disease
but there were a small number of men that died from fatal
heart attacks taking Centrum compared to placebo which
was probably due to chance or luck or maybe not. Maybe
Centrum has some heart healthy features!
There has not been any other phase-3 like trials of
multivitamins in the U.S. or really around the world! The folks
jumping on the “let’s beat up the multivitamin bandwagon”
are really acting silly. Patients and other health care
professionals do not need physicians/researchers to act like
Democrats and Republicans fighting on 2 different television
channels but rather they need objectivity and education
on what to do with all this mess! The multivitamin chaos
was not just created by some members of the supplement
industry, but also by some members of my own profession.
Ask yourself these questions: Are you willing to pay pennies
a day to slightly and potentially reduce your risk of cancer
(even if you have been treated already) and cataracts (the
number 1 cause of blindness in the world and one of the
most costly annual Medicare procedures) with a pill that
has the same side effects as a placebo that does not show any
evidence to prevent other diseases right now? If the answer
is “yes” then great and if the answer is “no” then that is okay
too! My answer is “yes” and will stay “yes” until someone
shows me that the risk exceeds the benefit. The other reason
a multivitamin is interesting is because it is common now
to find out that many medications and even alcohol reduces
the amount of nutrients in the body. I was also expecting
to see, in this large multivitamin study, that men eating a
TON OF FRUITS AND VEGGIES per day did not appear
to benefit from taking a cheap old Centrum Silver, but it
appears they did just as much if not more than other men!
Hmmmmmmm! Got to go now and take my Centrum Silver
with my dinner!
276) Artificial sweeteners are bad for me and my cancer?
Really, and if you believe that I have the next tour leaving
in an hour to show you the Loch Ness Monster because
he is in my basement sink swimming around and reading
the newspaper.
(Reference: www.efsa.europe.eu/en/topics/topic/aspartame.htm)
BOTTOM LINE
Please do not worry about artificial sweeteners! Just be
happy! If the research changes I will let you know but for
now the EFSA did a really good review.
WHAT ELSE DO I NEED TO KNOW?
On December 10, 2013 my prediction came true (No, not the
one about Justin Bieber getting in trouble or the Roughriders
winning the Grey Cup or the Seahawks de-Broncoing the
Broncos because that had not happened yet)! Except no
one cared because there was weak media coverage and
this was not a controversial finding. The EFSA (European
Food Safety Authority based in Parma, Italy) announced
their investigation of aspartame (the artificial sweetener)
and found that it was SAFE for human consumption. “This
opinion represents one of the most comprehensive risk
assessments of aspartame ever undertaken” said the Chair
of the EFSA’s Panel Dr. Alicia Mortensen. A can of diet
soda contains 180 mg of aspartame, which means an adult
weighing 75 kilograms would need to drink more than 16
cans per day to exceed the EU acceptable daily intake level
(EU level is 40 mg per kg of body weight and the U.S. level is
50 mg/kg). Sorry, I realize artificial sweeteners are really an
easy target but in reality they are not absorbed by the body
and really do not change blood sugar or insulin levels and in
the case of aspartame it just consists of 2 little amino acids!
So, enjoy your artificial sweeteners because I am getting my
daily intake of them right now! Yummy! I am not worried
about any artificial sweeteners but my favorite one in terms
of taste and research is Stevia! Yummy! There are also a few
new ones out there that I will keep you up-to-date on! Of
course those with the rare medical condition like PKU have
to avoid certain amino acids (phenylalanine) and sweeteners
like aspartame. Otherwise it’s all pretty groovy folks!
On the other hand, if you think you can drink 7 diet sodas a
day and feel fine, you won’t and this is not due to the artificial
sweeteners but is due to the lifestyle that encourages this
kind of soda consumption. Someone that drinks too much
soda also tends to have other unhealthy behaviors going on
and a lack of good nutrition. So, basically you will feel about
as good as the Mayor of Toronto after the police discovered
the secret videotape but I digress (Man, those jokes never get
old)!
277) Whey Protein Isolate (WPI) or another protein
powder and when and why take it? What about chocolate
milk?
(Reference: Beasley JM, et al. Nutr Clin Pract 2013;28:684-690)
BOTTOM LINE
Sarcopenia is reaching epidemic proportions even in men
with prostate cancer in my not so humble opinion. Whey
protein isolate (WPI) and other powders are the most
concentrated protein sources available commercially with
little to NO SUGAR and can help with weight loss, and
muscle development. Look for a protein powder with
no sugar and over 20 grams of protein for about 100-125
calories. Chocolate milk is awesome, but if you are watching
your waist then all that sugar and calories is a problem.
WHAT ELSE DO I NEED TO KNOW?
Exercising before protein powder intake allows for greater
use of amino acids for muscle protein synthesis in both
young and elderly men. Aging is associated with an ongoing
reduction in skeletal muscle mass that is also known as
“sarcopenia” (literally means “lack of flesh”). One theory as
to why this occurs is that aging is associated with a greater
protein breakdown compared with production, which is not
observed in young adults. Men on hormone therapy for
prostate cancer have a huge problem with sarcopenia because
testosterone is needed to help combat muscle loss.
Remember (let’s review a past study I focused on a while
ago), in a wonderful recent study, a total of 24 elderly
individuals (average age of 74 years) were body-matched to
24 young controls (average age of 21 years). Subjects were
randomly assigned to the rest or exercise experiment, which
included consuming 20 grams (normal meal protein intake)
of a labeled protein at rest or after a single exercise task.
The exercise consisted of 30 minutes of moderate intensity
activity that included a combination of low-intensity cycling
and weight lifting. Muscle protein fractional synthetic rates
(FSRs) were also calculated, which can tell researchers if
protein is being used to potentially make some muscle.
www.paactusa.org • Spring 2014 / Prostate Cancer Communication 15
No differences occurred between protein utilization rates
between young and old regardless of rest or exercise. The
digestion and absorption kinetics are not different from a
young and older male AFTER consuming dietary protein,
especially right after exercise. Individuals should exercise
and then ideally consume some protein AFTER exercising to
permit a greater utilization of amino acids for muscle protein
synthesis. Additionally, getting some concentrated protein
after a workout can also suppress your appetite and help
further with weight loss.
Sarcopenia is a four-letter word in my vocabulary! And, the
only thing ever discovered by research to prevent sarcopenia
is weight lifting or some type of regular resistance exercise,
which can stimulate muscle tissue (we live in a use it or lose
it world). However, research has been accumulating over the
past several years that dietary or supplemental diverse amino
acid or protein ingestion may assist in preventing sarcopenia
when used with resistance activity or weight lifting. Although,
the ability to utilize amino acids in the muscle tissue appears
to become less efficient with aging in women and men (why
does everything get reduced or smaller with age except the
prostate?). Perhaps there is a way to trick the aging process
and ingest a moderate amount of protein right after exercise,
when tissue rebuilding and repair takes place. This is what
is suggested from this well-done study. And, I have to admit
that I am not waiting on a 10-year randomized trial, but have
already begun to incorporate this simple piece of advice for
myself, and all of the individuals that seek my advice. I just
finished a long work out and really wanted to have a Kit Kat
bar but instead had a strawberry whey protein isolate drink
that consisted of 125 calories and 25 grams of pure protein
with no sugar or fat and little sodium and I have to admit it
was really good. Using a high protein meal such as meat,
fish, beans, or just using whey or another low-calorie protein
powder (your choice) seems to give equivalent results to what
was found in the previous study I mentioned, if consumed
within about 30 minutes after your workout.
There is some recent hype from a small study of bicyclists in
the laboratory that suggests that chocolate milk is the best
thing to drink after a workout. This is interesting and it is a
choice but I do not think it is better than getting a whey, or
soy protein 8 ounce drink in water. For example, chocolate
milk can contain 200 calories or more while whey or soy is
about 100 calories. And, chocolate milk has less than 10
grams of protein while whey/soy contains around 20-25
grams of protein! Chocolate milk has about 30 grams of
carbohydrate and a lot of SUGAR (27 grams in one serving in
many cases - as much as Coca Cola or even more) and whey
and soy have little to no carbohydrates and fat and a little bit
of sodium and again works as an appetite suppressant. What
about protein bars? The only thing you should get from a
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Prostate Cancer Communication / Spring 2014 • www.paactusa.org
bar is a beer or fiber because most commercial bars have a
lot of protein but also a lot of SUGAR and calories (200-350
calories). So, I do not recommend most protein bars. Many
of us are working out to lose weight so picking a low calorie
and high protein powdered drink after exercise makes more
sense for many reasons. Next time you see me, I hope my
enhanced sized biceps and triceps do not scare you! Bring on
Mike Tyson (because I can run faster than him)!
278) LATEST NEWS FROM ASCO GU MEETING?
(Reference: American Society of Clinical Oncology Web Site)
BOTTOM LINE
There were some groovy research presentations at the
Annual ASCO GenitoUrinary Meeting in San Francisco, CA
this year. Here are some of the conclusions:
-Swedish research (abstract number 4) concluded the
following:
“Addition of local radiotherapy to hormonal treatment in
patients with non-metastatic advanced or high-risk prostate
cancer more than halved the 10 and 15 year prostate cancer
specific mortality and substantially decreased overall
mortality.” In other words, getting radiation treatment in
addition to hormone therapy provided a substantial benefit
in not only reducing the risk of dying of prostate cancer but
from dying earlier of all causes.
-There were several papers suggesting testosterone
replacement therapy (TRT) given to hypogonadal men or
men with abnormally low testosterone did not appear to
increase the risk of prostate cancer or of prostate cancer
returning after treatment. This is good news especially for
men with very low testosterone but this needs more studies
and it does not resolve the heart disease issues mentioned
earlier in this column.
-Dr. Scholz and others from Marina del Rey, CA (abstract
247) had an excellent paper showing that many men, almost
one in three, still respond well to Xtandi (enzalutamide)
and 21% had stable disease after failing other drugs like
abiraterone and chemotherapy. So, after failing other drugs
if it is true that about half the men can expect something
positive to happen with the drug Xtandi then this is great!
However, it would also be interesting to know how many
men no longer responding to Xtandi would then respond to
abiraterone or chemotherapy (vice versa).
-Research from Japan (abstract 87) showed that after 1 year
on hormone therapy many men have large increases in deep/
visceral AND superficial/subcutaneous belly fat (32-35%
increases) and increases in bad cholesterol, triglycerides, and
blood sugar. This is not surprising or shocking in terms of
cholesterol but what is surprising is that men gain a lot of fat
quickly if they do NOT AGGRESSIVELY EXERCISE WHEN
ON HORMONE THERAPY! In the Dr. Moyad world no
one receives hormone therapy unless they agree to exercise
daily and lift weights twice a week (as long as they get doctor
clearance and do not have bone metastasis).
-Abstract 43 was a great review of the cheap blood test
C-reactive protein (CRP), which appears to have some ability
to predict overall survival in men with metastatic prostate
cancer from preliminary research (higher values are more
concerning), but a large prospective study is needed and it is
interesting work.
WHAT ELSE DO I NEED TO KNOW?
I have written too much for this issue and my fingers hurt. I
need to take a 3-month break before writing again. However,
I love you all like family and I will see you soon!
THAT IS ALL FOLKS!
See you this SUMMER, when I will write about many other
serious issues and give timeless advice in the next newsletter,
such as: why it is never smart to drink 2 gallons of water
wearing really tight jeans on a 4-hour airplane flight with the
airplane bathroom out of service or why it is not smart to live
in Michigan in the winter (especially during 2014) and forget
to buy 20 pairs of 10-inch thick thermal underwear! HAPPY
SUMMER - SOON I HOPE!
CHALLENGING PC TREATMENT
BIASES – IS NOTHING SACRED?
BOB LEIBOWITZ, MD (DR. BOB) • COMPASSIONATE ONCOLOGY MEDICAL GROUP
LOS ANGELES, CA • WWW.COMPASSIONATEONCOLOGY.ORG
Please note the following corrections to Dr. Bob’s Dec 2013
article (Volume 29, Number 4) “Dr. Bob’s Treatments and
Insights Regarding Prostate Cancer”:
Begins the middle of 3rd Paragraph of article (Left most
column page 3) should be replaced with:
Far too often, I consulted on prostate cancer patients who had
a radical prostatectomy initially, but a few years later when
their PSA’s rose, they were then often treated with radiation
therapy; and when their PSA’s again rose, they were finally
treated with hormone blockade.В They were not cured with
surgery and/or radiation therapy, but still had the side effects
from “curative intent” local radical therapies. These side effects
often included impotence, incontinence of urine, fecal soilage,
urinary discomfort and many other problems.
Rightmost Column page 5 – Item Number 6), should be
replaced with:
6. В When prostate cancer patients are treated with intermittent
androgen blockade (IAB), the time spent “on” hormone blockade is prolonged, while the time spent “off” hormone blockade
shortens.В This clearly demonstrates progression to CRPC.
M
ost prostate cancer (PC) patients have acquired quite a
bit of knowledge regarding the “best” way to administer
hormone blockade. The answer to this question is obvious…
whether you choose continuous androgen blockade (CAB)
or intermittent androgen blockade (IAB) is determined by
whichever way you and/or your doctor decide is best. Other
less opinionated patients might chain themselves to their
internet portal device and try to quickly read a few million
abstracts describing the
benefits and risks in the Dr. Bob’s Acronyms:
battle between CAB vs. PC..........Prostate Cancer
IAB, as they struggle CAB........Continuous Androgen Blockade
Androgen Blockade
to educate themselves IAB.........Intermittent
HB..........Hormone Blockade
on this contentious but CRPC ......Castrate Resistant Prostate Cancer
critically important issue. PSA........Prostate Specific Antigen
T............Testosterone
In the last issue of PAACT NCCN......National Comprehensive Cancer Network
from Dec 2013 (vol 29 ASCO.......American Society of Clinical Oncology
#4), I expressed my very IRB.........Institutional Review Board
COMG......Compassionate Oncology Medical Group
strong opinions regarding TRT.........Testosterone Replacement Therapy
hormone blockade (HB). BAT.........Bipolar Androgen Therapy
Deprivation Therapy
The reader may recall that ADT........Androgen
AAC.........Anti-Androgen Cocktail
I feel certain that CAB is PAP........Prostatic Acid Phosphatase
the least effective form of AUA........American Urological Association
AS..........Active Surveillance
HB; IAB is better, but every NCI ........National Cancer Institute
study testing IAB clearly Tax.........TaxotereВ®
2
demonstrates that your mg/m ...Milligrams Per Meter Squared
BSA........Body Surface Area
time on HB lengthens, UCSF.......University of San Francisco
while your time off HB CT...........Chemotherapy
shortens. Each subsequent
cycle, consisting of 2 phases - on-HB followed by off-HB, results
in shorter durations off treatment, longer durations on HB,
PSA nadir levels that get higher with each cycle of HB – by
definition, this is the classic progression that results in castrate
resistant prostate cancer (CRPC). As I noted, I feel strongly
that the most effective form of HB is a third choice – to use a
single cycle of Triple Hormone BlockadeВ®/Leibowitz Protocol,
then do everything possible to prevent or postpone having
www.paactusa.org • Spring 2014 / Prostate Cancer Communication 17
to go back on HB. And if you are ever urged to start another
cycle of HB, you should instead insist on being treated with
my 3-Pronged treatment protocol. It is my opinion that
this is clearly the most effective and best way to use HB and
always remember my first rule: “Everyone is entitled to their
own opinion. Their own WRONG opinion.” Corollary:
“Especially me.”
As I explained in the last issue of PAACT, in my very strong
opinion, the longer you are on HB, the more your illness is
evolving into CRPC. Each month on HB brings you 1 month
closer to CRPC and a shortened survival. The definition of
CRPC is a rising PSA while you are on HB. If your doctor can
find effective treatments that can delay or better yet, prevent
the need to go back on HB, then by definition, you will not
evolve into CRPC, since a rising PSA with normal or elevated
testosterone levels is not CRPC. Every month a prostate cancer
patient survives with a normal or even better supraphysiologic
level of testosterone (T), is one additional month of survival…
as opposed to when he has a rising PSA on HB, which, in my
opinion, will shorten his survival one month.
Until the past several years, the near universal opinion of
academic prostate cancer experts, along with almost the same
percentage of clinicians (or at least that is what they wrote and
said) was that IAB should be considered experimental and
should not be used outside of an experimental (Institutional
Review Board {IRB} approved) study.
In the late 1990’s, I was honored to be an invited speaker and
panel participant at the annual Massachusetts Prostate Cancer
Symposium. Some of the other panelists included Dr. Marc
Garnick, A professor at Harvard Medical School whose
predominant interest is urologic oncology, with a specialization
in clinical investigation related to prostate cancer. We both had
spent time (he still does) at the Harvard Medical School affiliated
Beth Israel Medical Center. Other panel members included a
family practitioner; a patient care advocate who was a prostate
cancer survivor; a well-known, highly regarded academic
urologist; a few other members that I sincerely apologize to
because I have forgotten their names. Most impressive to me,
our panel was privileged to have Dr. Anthony V. D’Amico, MD
PhD, participate. He is, without doubt, one of the absolutely
most brilliant and nicest people I have ever been blessed to
know. He very likely is among a handful of the “all-time best”
radiation therapists in the world; he is affiliated with Dana
Farber/Harvard Cancer Center as well as Brigham and Women’s
Hospital (both Harvard affiliated and I had the privilege to spend
6 months of my fellowship at these institutions). Dr. D’Amico
has been a major contributor in countless ways helping to better
treatment and control cancer along the entire spectrum of
malignant disorders. His research in PC therapy is one of his
major areas of expertise, resulting in major advances in patient
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Prostate Cancer Communication / Spring 2014 • www.paactusa.org
care, as well as in the basic science of PC. One of his major PC
contributions is known as the D’Amico classification scheme
dividing new patients with prostate cancer into 3 separate, welldefined prognostic categories: Low Risk, Intermediate Risk, and
High Risk. Yes!!! That D’Amico – impressive, huh?
The final panelist, equally as impressive to me, was also our
moderator, Dr. Philip W. Kantoff. Like many of the other
panelists, he is a professor in the Department of Medicine of
Harvard Medical School. He was also the Director of the Lank
Center for Genitourinary Oncology at Dana-Farber Cancer
Center, and is one of the most respected and knowledgeable
prostate cancer experts in the world.
The Symposium started with each panelist delivering their
prepared talks and slide presentations. Following this, Dr.
Kantoff, as moderator, lead us to discuss a number of controversial
issues based on an imaginary (or actual) prostate cancer patient
from his clinic who required a treatment recommendation at
various stages of his illness. My most vivid memory involved
Dr. Kantoff asking us about the type and manner of HB that we
recommend for our patients.
1)“Who would treat this patient with IAB? Who would advise
CAB??”
Never being shy, my hand did not even wait for the entire question
to be asked or even for my brain to select an answer before it shot
upward, almost pulling me off my chair.
“IAB” my hand seemed to force my mouth to yell out. The rest of
the panel absolutely and unanimously disagreed with my hand and
my mouth.
Next question:
1)“What type of patient on hormone blockade, in your practice,
do you believe is a candidate to be treated with IAB?”
That same hand acted without hesitation, and Dr. Kantoff allowed
me (reluctantly?) to answer:
“All of them!” Surprisingly, none of the panelists shared this belief
and once again they unanimously chose the exact opposite answer.
2) “Does anyone have any patient in their practice on IAB?”
Hand – yes
Everyone else – no!!!
And finally,
3)“Does anyone believe that at any future time they will ever use
IAB in their practice?”
Only my hand rose. The unanimous opposition party that
comprised all of the panelists, except Dr. Bob, only raised their
hands when the offered choice was “No”; they cannot conceive of
a time when they would ever treat any patient in their practices
with IAB, instead they confirmed that they would always advise
their patients to use CAB, and never to use IAB.
About 4-5 years ago, I was reading a medical journal that
published the authoritative National Comprehensive Cancer
Network (NCCN) treatment guidelines for various cancers
and that issue addressed the use of hormone blockade (HB) for
prostate cancer patients. One of the authors was Dr. Kantoff.
In spite of any differences of opinion we have had, he and
I both know that he is far more intelligent than I am; that he
has devoted his life to determining and proving scientifically,
exactly which treatments are most effective and/or least toxic
for every stage of prostate cancer, as well as a large number of
other types and stages of cancer. His efforts benefit prostate
cancer (and other types of cancer) patients everywhere; he
advances scientific knowledge benefitting society by following
the scientific method; leaving nothing to chance; proving each
and every step by creating treatment protocols, participating
in them, supervising them, analyzing their results, and then
presenting the results at conferences and/or publishing these
results in peer reviewed journals, textbooks, symposiums, while
always ensuring that the rights and privacy of every patient
remain his primary concern. I am sure that I omitted countless
other major contributions that were, are and will be made by Dr.
Kantoff, but not intentionally (it is 2am).
Back to the NCCN guidelines for using HB to treat prostate
cancer that I believe appeared in an April edition; they gave
the exact same recommendation that had been articulated by a
panel at the ASCO Prostate Cancer meeting in February of that
same year (and Dr. Kantoff had expressed that same opinion).
“CAB should be considered the standard of practice for prostate
cancer patients requiring HB. IAB should be considered
experimental and should not be given outside the context of an
IRB approved clinical trial.”
Nothing (yet) had changed for more than 15 years. But about 3
months later, I was reading (I think) a newspaper-type journal,
probably “Oncology Times,” and I noticed a picture of Dr.
Kantoff along with an article about HB. The author quoted Dr.
Kantoff and I paraphrase:
“Intermittent Androgen Blockade is at least as effective as CAB;
and probably better.”
Shocked but ecstatic and so pleased, I immediately wrote a letter
to Dr. Kantoff asking him to please let me know if the article was
accurately quoting him regarding the type of HB he advises. He
promptly wrote back to me saying that in general the article was
accurate, although in a few uncommon HB settings, he might
have some reservations about using IAB.
Around 1995, I had written that I believed IAB would eventually
be shown to be superior to CAB, and in either 2008 or 2009, I
was advised by Dr. Kantoff and others that soon to be reported
studies were able to conclude that IAB should no longer be
considered investigational. Over the next few years, IAB was
generally considered the “standard of practice” method to
prescribe HB. In January 2014, at the ASCO prostate cancer
conference in San Francisco, more than 90% of the audience
of physicians agreed that IAB should be the preferred way to
use HB, rather than CAB. Please remember that it takes an
extraordinarily long time for doctors to change their treatment
preferences/prejudices.
Later in this paper, I will present case reports from our own
practice that will provide some insight into my choice for
the title of this article. I used this same title in 2003 at
the annual Massachusetts Prostate Cancer Symposium.
The Symposium was sponsored by Massachusetts General
Hospital Cancer Center, Dana-Farber Cancer Institute, Beth
Israel Deaconess Medical Center, Dana-Farber/Harvard
Cancer Center, American Cancer Society, Tufts-New England
Medical Center, Massachusetts Prostate Cancer Coalition,
Massachusetts Department of Public Health, New England
Coalition for Cancer Survivorship, American Foundation of
Urologic Disease, and several more. There were two invited
keynote speakers for this meeting: Dr. Philip Kantoff and myself
(“Dr. Bob” Leibowitz.) This was the first national conference
where I had the privilege to be a keynote speaker and I felt
that this was the ideal format to present my interpretation and
analysis of the medical literature regarding testosterone and its
interactions in PC patients at different times in their evolution,
from hormone sensitive disease to hormone refractory and
maybe back towards hormone sensitive again. This evolution
results in HB betraying you and becoming a Benedict Arnold
as it switches from killing PC cells to helping PC cells, and
to seemingly becoming invincible – fortunately enormous
advances in understanding these changes continue to result
in more FDA approved effective treatments to help men
to defeat their own evil Benedict Arnolds. We cannot cure
metastatic PC, but our increasingly realistic goal is to change
it to a chronic disease (like high blood pressure or adult onset
diabetes mellitus) that you can live with and die with, but not die
from. At Compassionate Oncology Medical Group (COMG),
we continue to make extraordinary, compelling and impressive
progress, as we endeavor daily to make even more effective
advances for each of our patients along this path. We design
individualized treatments; we never use institutionalized, rigid,
recipe-book-type (“cookie-cutter”) fixed protocol approaches
that force the participating study doctors to become robotic, and
not allowing carefully crafted and studied creative innovations.
www.paactusa.org • Spring 2014 / Prostate Cancer Communication 19
The standard of practice protocols that are FDA approved only
improve the median survival of PC patients by 2.5 months
compared to placebo. The standards of practice that were
used before the approval of TaxotereВ® in May, 2004 to treat PC
patients had never been found to prolong survival in PC. Prior
to May 2004, no treatment for PC ever prolonged survival. I
began to exclusively use TaxotereВ® to treat all my PC patients
who needed chemotherapy beginning in 1997, seven years
before the FDA approved it for PC. Our use of TaxotereВ® as part
of my 3-Pronged protocol and our own modifications to reduce
side effects, while markedly improving its effectiveness, is a
major reason that patients continue to travel literally thousands
of miles to see us. Please see our map on our Compassionate
Oncology website that identifies the various countries and states
that are home to our patients. More than 75% of our patients
are not living in Los Angeles.
At the January 2014 ASCO prostate cancer conference in San
Francisco, CA, there was a poster presentation by Dr. Samuel
Denmeade, Professor of Urology and Pharmacology at Johns
Hopkins. His paper reported on their ongoing study that
investigates the effect of rapid cycles of very high levels of T
followed by a cycle of HB with castrate levels of T. Their study
tries to determine if PC growth might respond to their unique
and previously untested theories. The poster describes their
approach and results:
Authors of numerous medical articles that were published in
the 1940’s, 1950’s, 1960’s and literally through today, reported
that testosterone in some patients and at some stages of PC
stimulated cells to grow, while in other situations, testosterone
inhibited the growth of PC cells; and in the lab, the effect of T on
PC cells follows a bell shaped curve…low levels of T stimulate
PC cells to grow while high levels of T inhibit the growth of PC
cells and the higher the level of T, the greater inhibitory effects
on PC cell growth. This effect follows the classic example of a
bell shaped curve. The same effect is seen when breast cancer
cells are exposed to varying concentrations of estrogen. Low
levels of estrogen stimulate breast cancer cells to grow, but high
levels inhibit the growth of breast cancer cells; the higher the
level of estrogen, the greater the amount of inhibition.
oMust be on continuous androgen deprivation therapy
(ADT) for greater than or equal to 1 year.
o Rising PSA
o Less than or equal to 5 total bone metastases and less than or
equal to 10 total lymph node or soft tissue metastases.
oNo worrisome lesions (high risk), e.g., spinal cord
compression, urinary tract obstruction
oPrior second line hormone therapy and/or prior
chemotherapy allowed
o No pain
To find the specific medical references that confirm these
“claims of mine” and will convince my loudest and most
skeptical critics, please read the articles that I have posted on
our Compassionate Oncology website, including “High Dose
Testosterone & Prostate Cancer: Wait until you read this
update,” “High-dose Testosterone Replacement Therapy and
Prostate Cancer,” “TRT Case Reports: High-Dose Testosterone
Replacement Therapy (TRT) and Prostate Cancer (CaP),” and
“Testosterone Replacement in Prostate Cancer Survivors with
Hypogonadal Symptoms” (BJU article May 2010; coauthored
with Dr. Tanya Dorff, et al.). Also, see “Hormone Blockade:
Continuous, Intermittent or?” and for 3-Pronged Approach case
studies, read “Compassionate Oncology’s Latest Three-Pronged
Approach Patient Case Studies.” You can also find them in the
various DVD lectures that I have given (available FREE (only
pay S&H) by calling our office or ordering on our website):
DVD #4 (high-dose TRT), DVD #5 (IAB and high dose TRT),
DVD #6 (high dose TRT and 3-Pronged), DVD #7 (high-dose
TRT) and AAC, DVD #8 (3-Pronged), and DVD #9 (high-dose
TRT and 3-Pronged). Our latest DVD will be coming out very
soon – you can call our office to preorder your copy today.
20
Prostate Cancer Communication / Spring 2014 • www.paactusa.org
• Men with CRPC could respond to rapid cycling between polar
extremes of supraphysiologic and castrate T levels [Bipolar
Androgen Therapy (BAT)].
• Rapid cycling disrupts adaptive auto-regulation of AR.
• They call this “The Love Study”
• Eligibility criteria:
Men were started on T injections to achieve supraphysiologic
levels of T above 1500 ng/ml (“normal” is usually about
300-800 in many labs).
A TRT Case Report from COMG:
S. B.
12/95:
7/03:
52 years old; GS 3+3/6 at John Hopkins Hospital;
PSA = 7.3
5 mos. 2-drug hormone blockade Then saw Dr. Bob and was treated with 9 mos. Triple Hormone BlockadeВ®, followed by ProscarВ®
alone (Finasteride MaintenanceВ® Therapy)
Started high dose TRT; later added in some AntiAngiogenic Cocktail (AAC)
Date (month/year)
9/03
11/03
1/04
3/04
5/04
7/04 (thalidomide 50mg added)
9/04
11/04
1/05
T
1498
1545
1539
2062
1043
3678
1540
2674
1214
PSA
8.11
5.7
7.1
5.6
8.35
7.32
8.66
8.59
7
Date (month/year)
3/05
4/05
6/05
8/05
11/05
12/05 (LeukineВ® added)
1/06
2/06 (thalidomide stopped; RevlimidВ®
5mg/day started)
3/06
4/06
5/06
6/06
T
1286
2237
1232
2068
1427
1474
2212
PSA
7.12
6.4
7.57
9.19
9.01
11.1
11.5
3181
9.25
2791
2059
1599
1863
6.92
7.8
7.62
6.99
Eleven years after his diagnosis of PC, he never received local
treatment. His treatment was one 14-month cycle of HB and
3 years of high-dose TRT, along with some AAC. He expired
unexpectedly, apparently in his sleep, and was found by his
sister when he failed to show up at a restaurant where they
planned to meet.
Excerpts from his autopsy report:
“Mr. B--- was diagnosed with moderately differentiated
adenocarcinoma of the prostate gland circa 1996 and he has
been under treatment since that time. At autopsy, there is no
evidence of recurrent or residual tumor. The prostate gland
demonstrates only benign stromal and glandular hyperplasia
with no evidence of malignant tumor.”
“In this case, Mr. B--- had 90% and 85% luminal compromise
of the right and left coronary artery systems, resulting in
greatly reduced oxygenated blood flow to the heart muscle
(myocardium), and this in concert with hypertension placed
him at great risk for a sudden, irreversible, fatal cardiac
arrhythmia or clinical heart attack.”
“Forensic Elements and Consultations: … Medical records:
Limited records, primarily medication lists and records from
Dr. Leibowitz office are received, reviewed, and retained in the
autopsy file.”
I spoke to the pathologist before he started to do this patient’s
autopsy. He understood that the reason we asked for an autopsy
was to determine if there was any evidence of PC:
1) In this man’s prostate gland – he said that normally
they would cut the prostate into 2 equal parts – like an
opened oyster with a top and a bottom. Instead he cut
the entire prostate gland into 1 mm slices. This is the
same technique that is done with a radical prostatectomy
specimen. The finding: no PC anywhere in the prostate.
2) All of the lymph nodes that drain the prostate were sliced
like salami. The finding: no PC cells.
3) Knowing that PC spreads to bone preferentially and
especially to the vertebra of the spine, he carefully
sectioned each vertebral body longitudinally trying
to identify anything that could be metastatic PC. The
finding: absolutely no evidence of any PC cells anywhere
in this patient’s body.
The cause of death was severe advanced bilateral coronary
artery disease with 90% obstruction of the right coronary
artery and 85% obstruction of the left coronary artery. These
narrowed coronary arteries caused either a sudden fatal rhythm
disturbance of the heart (like ventricular fibrillation) or a clinical
heart attack (myocardial infarction).
This is a case of low-risk PC treated without any local therapy.
The patient only received 14 months of HB and later the AntiAngiogenic Cocktail (AAC). The autopsy confirmed that he
had a pathologic complete response to these medicines alone.
Please note that I (Dr. Bob) have been using high-dose
Testosterone Replacement Therapy (TRT) on select PC
patients in our practice since the late 1990’s. I vividly recall
my first PC patient starting on TRT; my target T range was
only 100-200. Over the next 6 years or so, I slowly raised
the target T level, while always requiring oral and written,
informed consent detailing all risks/benefits and treatment
options. We also ordered extremely frequent labs, as well as
scans and office visits. When a patient was started on TRT,
we initially required weekly labs, including PSA and T levels.
If there were not any problems, we gradually lengthened the
intervals between their blood tests, but even today, the least
often that labs are checked is monthly. We were surprised
to find that for most patients, PSA levels did not increase in
spite of rising T levels. However, in patients who still had
an intact prostate gland, their T levels began to rise after HB
was stopped or if they were being treated with TRT, the T
would always stimulate their normal prostate gland cells to
make PSA. HB does not kill normal prostate cells. Everyone
with a normal prostate gland will have their PSA’s increase,
usually starting about 2-5 months after HB is stopped. The
levels of PSA rise in what I describe as a “step and plateau”
pattern. Can HB cure PC? It certainly did for this patient.
Part three of this article will be printed in the Summer 2014
issue of the PAACT Newsletter.
В®Triple Hormone Blockade, Triple Androgen Blockade and
Finasteride Maintenance are the registered trademarks of
Robert L. Leibowitz, M.D.
www.paactusa.org • Spring 2014 / Prostate Cancer Communication 21
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