P A A C T,
I N C.
PROSTATE CANCER
COMMUNICATION
PROSTATE CANCER COMMUNICATION NEWSLETTER
•
VOLUME 20, NUMBER 2
•
June 2004
FOUNDER: LLOYD J. NEY, SR. – FOUNDED 1984
President and Chairperson:
Janet E. Ney
A STRATEGY OF SUCCESS - IN THE TREATMENT OF
PROSTATE CANCER
By Stephen B. Strum, MD, FACP
PART II
Board of Directors:
Edwin Kuberski
Treasurer
Newton Dilley
Helen Mellema
Peter Noor Jr.
Richard H. Profit Jr.
Anthony Staicer
After counseling thousands of men and their families from all over the United
States and abroad for over the last twenty years, a strategy associated with a successful campaign against cancer became apparent. What are the necessary ingredients of this successful strategy? There are six essential steps in this “roadmap”
to a successful outcome for the man with prostate cancer (PC):
1. LISTENING TO THE BIOLOGY OF CANCER.
2. VALIDATING CRITICAL DATA INPUTS.
Honorary Board Members:
3. ESTABLISHING A BASELINE.
Donald F. Mellema
Russell Osbun
Frank Perry
4. INTEGRATING
ANALYSIS.
Medical Advisory Board:
5. SYNTHESIZING ALL OF THE ABOVE DATA TO REPRESENT A
“REFINED” ANALYSIS.
Richard J. Ablin, Ph.D.
V. Elayne Arterbery, M.D.
Robert A. Badalament, M.D.
Duke K. Bahn, M.D.
Israel Barken, M.D.
E. Roy Berger, M.D.
Michael J. Dattoli, M.D.
Fernand Labrie, M.D.
Fred Lee Sr. M.D.
Robert Leibowitz, M.D.
Mark Moyad, M.P.H.
Charles E. Myers Jr. M.D.
Gary M. Onik, M.D.
Haakon Ragde, M.D.
Oliver Sartor, M.D.
Stephen B. Strum, M.D., FACP
Donald Trump, M.D.
Steven J. Tucker, M.D.
Ronald E. Wheeler, M.D.
INFORMATION
WITH COMBINED VARIABLE
6. PRESENTING STRATEGIES TO THE PATIENT WITHIN THE
CONTEXT OF HIS SITUATION.
In Part I of this three-part series published in the December 2003 issue of the
PAACT Prostate Cancer Communication, I introduced the reader to many foundational concepts involved in PC and covered Step 1 of the 6 steps listed above. A
concise review and embellishment of the contents of Part I will add to your understanding of Part II.
Out of the crisis of having a life-threatening illness such as PC comes the opportunity to focus on the integrity of your biological systems. The term Integrity is an
important one. This relates to knowing the truth about the status of a biological
system as well as heightening our attention to the fact that every system integrates
with other systems to allow for coordinated biologic actions. This is the ultimate
goal of medicine: to realize the holistic nature of health and the unity of all biological systems at every level of life. This is the heart and soul of integrative
medicine.
Let’s Conquer Cancer in OUR Lifetime
In our approach to the treatment of PC, the determination
of the extent of the cancer (staging) is our greatest weakness. In the year 2004, the staging of PC equates with doing a bone scan and a CT scan of the pelvis and abdomen.
These tests are too crude to appreciate small volumes of
PC outside the prostate gland and therefore they grossly
underestimate the extent of disease. Thus, many patients
are led down the proverbial garden path to selections for
local therapy that are not appropriate to their biological
status. Too often, after the failure of one local therapy, the
patient is again led to another local therapy. The realization is missing, or is being denied, that a local therapy
cannot eradicate disease whose extent is greater than the
scope of the surgeon’s scalpel, beyond the field of the radiation oncologist’s portals of treatment, or beyond the
borders of an iceball created by the cryosurgeon. Therefore, we must use our healthcare dollars wisely to make
advances in technology that lead to the development of
more accurate staging tools. We have effective methods to
eradicate PC, but the selection of a particular treatment is
often not appropriate to the stage or extent of the disease.
Step #2. Validating Critical Data Inputs
The Gleason Score (GS)
The process of validating key biological “inputs” involved in the prognostic equation is important. The GS
is one of the most important biologic clues relating to the
aggressiveness of prostate cancer. An accurate reading of
the GS is not to be taken for granted. Medicine has become more complicated, and the levels of skill of community pathologists and even academic pathologists vary significantly. Some pathologists are highly competent in
evaluating a specific disease(s), while others are not. Observer disagreement occurs even among experts, although
not usually to a major extent.37 Disagreement on GS between community pathologists and recognized experts in
the field, however, is significant.37 Therefore, validating
the Gleason score with an acknowledged expert in the
field of PC is a critical portion of successful strategy.37-40
Certainly, we should optimize our evaluation of the biologic process by understanding the variable talents that
exist everywhere and in every field. Obtaining a second
opinion from an acknowledged expert in the field of PC
pathology is a worthwhile investment. A listing of some of
the USA- and European-based recognized experts in prostate cancer pathology is shown in the tables.
Name of Pathologist
or
Lab
Europe
Helmut Bonkhoff
Burkhard
Helpap
Nicolas Wernert
Location
or Telephone
Center Name
bers
Num-
Frankfurt, Ger- 069/951 447-90
many
Singen,
Ger- 07731/892100
many
Bonn, Germany 0228/2875030
C A N C E R C O M M U N IC A T IO N
P a tie n t A d v o c a t e s f o r A d v a n c e d C a n c e r T r e a t m e n ts
1 1 4 3 P a r m e le e N W
G r a n d R a p id s , M I 4 9 5 0 4
D ir e c t o r … . R ic h a r d P r o f it
E d it o r … R ic h a r d P r o f it & S t a f f
W e b m a s t e r … A r t S c h le f s t e in
P o stm a s te r: S e n d a d d re ss c h a n g es to :
P r o s t a t e C a n c e r C o m m u n ic a t io n
P .O . B o x 1 4 1 6 9 5
G r a n d R a p id s , M I 4 9 5 1 4
P h o n e : 6 1 6 /4 5 3 - 1 4 7 7
F a x : 6 1 6 /4 5 3 - 1 8 4 6
E - M a il: p a a c t @ p a a c t u s a . o r g
P A A C T W e b P a g e : h t tp : //w w w .p a a c t u s a . o r g
N e w s le t t e r : h t t p : //w w w . p a a c t u s a . o r g
E d it o r :
A r t ic le s a u t h o r e d b y o t h e r t h a n t h e e d it o r m a y n o t f u lly r e f le c t
t h e v ie w s o f t h e c o r p o r a t io n b u t a r e p r in t e d w it h t h e u n d e r s t a n d in g
t h a t t h e p a t ie n t h a s t h e r ig h t t o m a k e h is o w n in t e r p r e t a t io n o f t h e
e f f ic a c y o f t h e in f o r m a t io n p r o v id e d .
I n a n e f f o r t t o c o n s e r v e s p a c e a n d b e a b le t o in s e r t a s m u c h
m a t e r ia l a s p o s s ib le in t h e n e w s le t t e r , r e f e r e n c e s f r o m v a r io u s
a r t ic l e s a r e in t e n t io n a lly o m it t e d . I f y o u w o u ld lik e t o o b t a in t h o s e
r e f e r e n c e s , p le a s e c o n t a c t P A A C T , w e k e e p a ll o f t h e o r ig in a l
a r t ic l e s a n d th e r e f e r e n c e s u s e d o n f ile .
INDEX
Page
1. A Strategy of Success in the Treatment of Prostate Cancer
(Stephen B. Strum, M.D., F.A.C.P.)
8. Early Hormonal Therapy Works Ridiculously Well (Robert
Leibowitz, M.D. and Steven Tucker M.D.)
12. What The Heck Has Been Going On In My World – Part
IV? (Mark A. Moyad, M.P.H.)
17. Media Release
18. LAC-PAACT UPDATE (Gregory H. Teufel, Esq.)
20. Board Certification What Does It Mean? (Stephen Barret,
M.D.)
21. Acknowledgements
23. Financial Summary Report
24. PAACT Dues Notification for 2004
Name of Pathologist or Lab
USA
David Bostwick
Francisco
J.
Civantos
Dianon Laboratories
Jon Epstein
David Grignon
John McNeal
Jon
Oppenheimer
UroCor Laboratories
Location or Cen- Telephone
ter Name
Numbers
Virginia
U of Miami
800-214-6628
305-325-5587
Connecticut
John Hopkins U
U of Michigan
Stanford U
Tennessee
800-328-2666
(select 5)
410-955-2162
313-745-2520
650-725-5534
888-868-7522
Oklahoma
800-411-1839
A second opinion on the pathology is usually covered by
insurance but if not, runs about $300-$500 depending on
what is done. A copy of the original pathology report with
the actual slides or recuts from the tissue block are sent to
the outside reviewer. A copy of the insurance information
is usually sent along with this. Your primary care doctor
or specialist can initiate a 2nd opinion but you need to request this and ask for a specific physician or lab to be
used. Additionally, other prognostic tests such as p53,
p27, BCL2, Ki 67, and DNA (ploidy) analysis can also be
done by some of the above pathologists and labs using the
tissue blocks. There are extra charges for these services.
Call the phone numbers shown in the tables for more information.
Step #3: Establishing a Baseline
A truer picture of the patient’s status evolves when we (1)
listen to the biology of PC and employ the valuable tools
of PSA and its dynamics, (2) understand the use of the
clinical stage and its limitations, (3) obtain the prostate
gland volume and use the appropriate calculations to determine cancer-related PSA, and (4) keep in mind that the
Gleason score, one of the most important biologic expressions of prostate cancer, must be validated by an expert in
PC pathology.
The patient’s medical “story” becomes clearer as more
and more clues are revealed to help us solve his problem.
This is M.D. (medical detective) work and it is the crux of
outstanding medical care. This information is our baseline, or starting point. Years ago, the baseline would have
been limited to the findings of DRE and a pathology report. Now it has evolved to incorporate biological manifestations that allow us to tell so much more, or as Paul
Harvey used to say, “and now for the rest of the story.”
These baseline studies are valuable because they depict
the biologic reality of the individual patient, and because
they act as critical observation or comparison points to
evaluate the patient’s course of illness. This applies to periods of observation as well as when active therapy is underway. We have to be able to objectify the results of
our therapy. How can we know how much we have
helped the patient if we have no basis for comparison?
Core Percentage
The number of biopsy cores that exhibit PC at the time of
the diagnosis of this disease is an additional baseline input
of significant importance. Dividing the number of cores
that show prostate cancer by the total number of cores
sampled gives us the core percentage. The core percentage
relates to tumor density. It also provides a sense of tumor
volume. A core percentage involvement of 50% or higher
is an adverse prognostic finding that is reported in many
publications.41-51
DNA or Ploidy
Ploidy, in the context of PC, relates to the amount of DNA
present in the PC cell population being studied. A normal
ploidy status, or “diploid” state, occurs when the amount
of DNA within the tumor cell is normal. This is equated
with the tumor cell having the full complement of chromosomes e.g. 46, since the DNA or genetic material is
found within genes that are arranged on each chromosome. Cells are either “diploid” or normal in their DNA
amounts or abnormal i.e. “aneuploid.” Diploid status is
more commonly associated with tumors of a low to moderate Gleason score, whereas abnormal ploidy (aneuploid)
status is more commonly associated with tumors of a
higher Gleason score. The actual data involving the
evaluation of 35,931 biopsies is shown in the accompanying table. As can be seen from this data, ploidy analysis
would be especially helpful in patients with Gleason
scores ranging between 6 and 8.
Gleason Score vs Probability of Diploid vs Aneuploid ***
Gleason
Diploid
Aneuploid
Number of BiScore
opsies Evaluated
2-5
85%
15%
564
6
62%
38%
15,999
7
33%
67%
12,768
8
22%
78%
4,433
9-10
13%
87%
2,167
Total
35,931
*** Table from PCRI Insights, Vol 4, No.1 Jan 2001, page
4, table 2. Data from UroCor, Inc.
Although DNA analysis or ploidy is often criticized as not
being a useful prognostic factor in prostate cancer, there
are far more compelling studies that would suggest that
the DNA status of the tumor cell population tells us much
about the aggressiveness of the individual patient’s PC. 5280
Ploidy analysis can be done on the diagnostic biopsy or
from PC tissue obtained at the time of RP. Normal DNA
or diploidy is associated with a better prognosis and a
better response to therapies involving androgen deprivation therapy. Abnormal DNA or aneuploidy is associated with PSA recurrence after RP in a large series from
the Mayo Clinic. 66,67 These landmark papers substantiate
the value of the ploidy analysis, although others dispute its
significance. In this paper, Lerner et al clearly demonstrated the importance of ploidy as an independent prognostic factor. The 5-year relapse rates in patients undergoing RP and having "apparent" OCD were analyzed with
respect to PSA, GS and ploidy status. A significantly
higher rate of disease relapse was seen in patients with
non-diploid (aneuploid) tumors. This is shown in the accompanying table.
Risk Factors for Progression in Patients with Prostate Cancer Treated with Radical Prostatectomy
with Apparent Pathologically Organ-Confined Disease (after Lerner, et al.)
PSA Level Prior to RP
Percent Progression Within 5 Years of RP
Ploidy Status at RP
PSA
< 10 ng/ml
> 10 ng/ml
Gleason
Score Diploid
at RP
Aneuploid
5
8%
15%
6
15%
30%
7
30%
42%
8-10
42%
61%
5
15%
30%
6
30%
61%
7
42%
61%
8-10
61%
61%
Using the PSA prior to RP, the Gleason score at the time
of RP and the ploidy status of the RP specimen, the risk of
any kind of disease progression (biochemical or clinical)
was significantly correlated with ploidy status. Recent
DNA analyses have shown an excellent correlation between ploidy analysis obtained from biopsy specimens and
the subsequent RP specimens. Therefore, in the setting of
what appears to be organ confined PC, the use of DNA
analysis is a valuable tool for the PC patient and physician. Modified after Lerner, et al.66
Pyrilinks-D (Dpd or deoxypyridinoline)
This is an important baseline assessment. Pyrilinks-D
quantitates the amount of bone breakdown or resorption. It
measures a fragment of the bone matrix that is excreted
into the urine. Therefore, in situations of excessive bone
resorption or breakdown, the Pyrilinks-D or Dpd is elevated. In men, this is greater than 5.4 nmoL Dpd per
nmoL urine creatinine. Increased Dpd is also commonly
seen as a result of the use of androgen deprivation therapy
since a lack of testosterone favors osteoclast activity,
which promotes the breakdown of bone.
Excessive bone resorption is associated with a greater risk
of osteoporosis. However, at the time of diagnosis, prior
to any therapy, elevations in Dpd have been associated
with metastatic disease to bone. This is not an absolute,
but it is a risk factor that is put into the equation of how
we assess patients and how we counsel them to treat the
entire disease process.81-83
Nationwide laboratories for two patient service centers
doing the Pyrilinks-D urine test include Quest Diagnostics
and LabCorp. The URLs for these labs are:
http://www.questdiagnostics.com/patient/index.html) and
(http://www.labcorp.com/locator/). Information for additional laboratories may be obtained by emailing
info@dpcweb.com. Please note that the Pyrilinks-D urine
test requires a sample obtained from the second-voided
urine specimen upon arising out of bed; it does not require
a 24-hour urine specimen. The cost of the Pyrilinks-D or
Dpd test is approximately $30 and is covered by Medicare. Remember to remind the laboratory NOT to confuse
the Dpd (deoxy-pyridinoline) test with the older pyridinoline test.
We now have tools to improve the bone environment.
These are the class of compounds called the bisphosphonates of which Fosamax, Actonel, Aredia and Zometa are
examples. Used in combination with bone supplements
such as Bone AssureВ® (Life Extension Foundation) and
Bone UpВ® (Jarrow Inc), and with exercise, we can stop
bone resorption and hopefully decrease the spread of PC
to bone. If we do not use tests such as Pyrilinks-D (Dpd)
prior to, and during treatment with bisphosphonates plus
bone supplementation, we have no objective means to ascertain that treatment has accomplished its goal. Therefore, obtaining a baseline Pyrilinks-D is an important
starting point to correct what needs to be fixed within the
health of the patient.
These are the five major available bisphosphonate compounds in the world today. Clodronate, Alendronate
(Fosamax) and Risedronate (Actonel) are oral agents.
Their bioavailability may be affected by gastrointestinal
absorption. However, using the Pyrilinks-D test the effi-
cacy of any bisphosphonate compound can be assessed.
Pamidronate (Aredia) and Zoledronate (Zometa) are administered intravenously. Detailed discussion of the
bisphosphonate compounds and information regarding
administrations can be found in “A Primer on Prostate
Cancer, The Empowered Patient’s Guide” by Stephen B.
Strum and Donna Pogliano. This is available via
www.amazon.com or through Life Extension Foundation
at 1-866-820-7457.
QCT Bone Densitometry
Not only does the status of the bone environment appear
to be important in the potential spread of PC, but also it
appears that bone loss is an epidemic disease in men with
PC prior to the initiation of any type of PC treatment. Using the superior technology of quantitative CT bone mineral density to assess bone loss, Smith et al showed that
95% of men diagnosed with PC had either osteopenia
(32%) or osteoporosis (63%). In the same patients, the
current “standard” of DEXA bone densitometry, indicated
that 29% of men had osteopenia but only 5% had osteoporosis.84 Establishing a baseline using the superior technology of QCT bone density scanning prior to any kind of
therapy may not only enhance the outcome of the PC patient if abnormality is detected and corrected, but also it
may prevent the complications associated with osteoporosis. Information on QCT bone density testing sites can be
obtained from Mindways Software, Inc. (1-877-646-3929
or www.qct.com) and at Image Analysis, Inc. (1-800-5484849 or www.image-analysis.com)
Testosterone Levels
An additional area that is critical to an understanding of
PC as it relates to treatment with androgen deprivation
therapy (ADT) is obtaining a baseline testosterone level.
95% of the time we see men receiving ADT––therapy
targeted to deprive androgens such as testosterone,
DHEA-S and androstenedione––and note that the patient never had a baseline testosterone level or one obtained after initiating ADT. PC patients presenting with
low baseline testosterone levels at diagnosis have been
found to have higher Gleason scores. Schatzl determined
that the mean Gleason score averaged 7.4 in such circumstances versus 6.2 when the baseline testosterone levels
were normal.85 Other investigators have found a correlation between low free serum testosterone at diagnosis and
more extensive PC as well as a higher percentage of PC
that shows a GS of 8 or greater.86
Prostatic Acid Phosphatase (PAP)
Prior to the advent of PSA testing, the major blood marker
reflecting prostatic cancer activity was the prostatic acid
phosphatase, or PAP. This is an enzyme level that is obtained from the patient’s serum. Many physicians have
discounted the PAP, while many others still use it as a
differential tool in their strategic analysis of the patient. In
their experience, the PAP is an important baseline test
since it has predictive value regarding the success or failure of RP or RT.87-89 In the study by Moul, et al., values
of PAP at baseline of 3.0 or higher were associated
with more than a two-fold risk of PSA recurrence after
RP, even if the baseline PSA was 10 or less.88 In the
study by Han, et al., a striking relationship between
baseline PAP using the enzymatic method of Roy and
PSA recurrence post RP was seen. Clearly, the importance of this baseline biomarker must be emphasized and
utilized in an intelligent strategy to maximize a successful
outcome for the PC patient.
Baseline
Freedom from
PAP
(Roy
Biochemical Recurrence After RP
assay)
At
10
U/liter
At 5 Years
(p value)
Years
87% (84- 77% (73- p
=
<0.4
89)
81)
0.0001
79% (75- 65% (59- p
=
0.4-0.5
83)
70)
0.0001
63% (52- 44% (30- p
=
>0.5
72)
57)
0.0001
PAP and Freedom from Biochemical Recurrence after
RP
In a study from the Johns Hopkins Medical Institutions
involving 1,681 men, PAP levels obtained prior to RP
were predictive of patient outcome.89 In this study spanning the years 1982-1998, the PAP methodology employed
was based on an enzymatic assay described by Roy, et
al.90 in contrast to present-day methods which use immunoassays.88 In the original paper by Roy, the mean PAP
for normal healthy men was 0.28 В± 0.09 U/liter with a
range from 0.11 to 0.60. In the Hopkins study, freedom
from biochemical recurrence at five and 10 years after RP
was 87% and 77% for those men with normal pre-RP PAP
levels defined as <0.4. However, this dropped to 79% and
65%, respectively, in men with preoperative PAPs of 0.4
to 0.5 U/liter and even further to 63% and 44% in those
with baseline PAP levels of > 0.5 U/liter. This is the 3rd
study to show the significance of baseline PAP testing in
the outcome of men with PC. In current times when
translational medicine is emphasized so often, such findings should be routinely incorporated into the clinical
care of men diagnosed with PC. After Han, et al. 89
Step #4. Integration of Information Using a Combined
Variable Analysis
Integrating and analyzing clinical and/or pathologic data
to enhance the generation of information that is more statistically significant has been termed “combined modality analysis” by Anthony D’Amico, M.D. Such an approach incorporates various biological evaluations of the
patient in order to project outcomes to be used as guides
for further evaluation and treatment purposes. In essence,
this is a deductive process of “Given these biological facts
of known significance that are unique to the patient’s
situation, what we can deduce is the reality for this patient
insofar as the extent of his disease and the probability of
success of various treatments that may be suggested.”
to look for patterns associated with a specific outcome are
very important advances. Some of the algorithms and neural nets that we have found helpful in integrating information (baseline and validated information) were discussed
in the PCRI Insights issue of May 2001. These are available from the PCRI website.
To recap, we have listened to the biology of this illness
called PC to obtain basic inputs of information such as the
PSA, DRE, GS, gland volume and core percentage. We
have invoked important principles of medical detective
work such as baseline studies, and validation of key bits of
information. We have integrated such data using tools
based on the vast experience of others. Such tools are now
conveniently used as software programs. These take the
form of nomograms, algorithms, and neural nets (see
www.pcri.org under the menu heading of “PC Tools” and
then “Software”). The outputs of such analyses become
“Status Level I.” These basically relate our assessment of
the extent of disease in the patient being studied. This
first level Risk Assessment is the first stage of our rocket
that we must achieve to optimize a successful outcome in
the care of the man with PC.
The output of these mathematical analyses provides a refined risk assessment. This logically leads your doctor to
obtain additional studies to exclude PC spread to areas
reflecting a significant risk of involvement, or on the contrary, to forgo such studies where the yield of finding abnormalities will be negligible (< 3%).
The results of this objectified risk assessment enables the
patient’s physician to fine-tune further evaluation and
management of the patient. This formalizes the analytic
process. It forces those involved in the patient’s care to
look at “the facts Ma’am, just the facts.” This methodological process is of paramount importance since the nomograms, neural nets and similar tools that have been
available utilize the inputs and outcomes of over 20,000
human lives in their generation of new data. This is not
mouse, rat or hamster data, but the experiences of men
with prostate cancer that can guide other men who come
after them. Thus, Level 1 embodies the philosophy of Santayana: “Those who cannot remember the past are condemned to repeat it.”
Physicians have actually been using a lower intensity form
of this kind of approach when they observe individual
variables such as the PSA, Gleason score, etc. What scientists like Partin and D’Amico and others have done is to
combine these variables and define risk-groups that relate
to particular outcomes for various therapies. In other
words, what treatment will be most successful for your
given biological profile. The outcomes may relate to the
findings at RP such as the probability of organ-confined
disease versus the presence of extra-capsular extension,
seminal vesicle or lymph node involvement. The outcomes may be expressed as the risk for PSA recurrence
after RP, RT or seed implantation. Many scientists are
also using additional statistical methods that go beyond
analysis of multiple variables. Their analytic approaches
are now being published in large numbers of papers.91-94
Approaches such as artificial neural nets that can be taught
This refined risk assessment profile, now developed specifically and individually for a particular patient, becomes
a custom profile. Rather than pigeonhole patients into
broad categories, it has presented the individual patient as
the unique biologic entity that he is. In addition, as mentioned previously, the patient is now taking advantage of
the past history and performances of other men in similar
prognostic risk categories. This historical data is the essence of what Partin, et al. first presented in 199395, updated in 199796 and again recently updated; this is what
we call the Partin Tables.97 The Partin Tables are the prototype of combined modality analysis.
This ends Part II in A Strategy of Success in the Treatment of Prostate Cancer. In the next issue of Prostate
Cancer Communication, steps 5-7 will be discussed.
Readers should reread Parts I and II and use The Primer
on Prostate Cancer as a basic guidebook as well as the
PCRI website to facilitate a full understanding of these
steps to optimize success in the treatment of this illness.
References
37. Wurzer JC, Al-Saleem TI, Hanlon AL, et al: Histopathologic review of
prostate biopsies from patients referred to a comprehensive cancer center: correlation of pathologic findings, analysis of cost, and impact on treatment. Cancer
83:753-9, 1998.
38. Steinberg DM, Sauvageot J, Piantadosi S, et al: Correlation of prostate
needle biopsy and radical prostatectomy Gleason grade in academic and community settings. Am J Surg Pathol 21:566-76, 1997.
39. Carlson GD, Calvanese CB, Kahane H, et al: Accuracy of biopsy Gleason
scores from a large uropathology laboratory: use of a diagnostic protocol to
minimize observer variability. Urology 51:525-9, 1998.
40. Kronz JD, Silberman MA, Allsbrook WC, et al: A web-based tutorial improves practicing pathologists' Gleason grading of images of prostate carcinoma
specimens obtained by needle biopsy: validation of a new medical education
paradigm. Cancer 89:1818-23, 2000.
41. Badalament RA, Miller MC, Peller PA, et al: An algorithm for predicting
nonorgan confined prostate cancer using the results obtained from sextant core
biopsies with prostate specific antigen level. J Urol 156:1375-80, 1996.
42. Borirakchanyavat S, Bhargava V, Shinohara K, et al: Systematic sextant
biopsies in the prediction of extracapsular extension at radical prostatectomy.
Urology 50:373-8, 1997.
43. Conrad S, Graefen M, Pichlmeier U, et al: Systematic sextant biopsies
improve preoperative prediction of pelvic lymph node metastases in patients
with clinically localized prostatic carcinoma. J Urol 159:2023-9, 1998.
44. D'Amico AV, Whittington R, Malkowicz SB, et al: Combination of the
preoperative PSA level, biopsy gleason score, percentage of positive biopsies,
and MRI T-stage to predict early PSA failure in men with clinically localized
prostate cancer. Urology 55:572-7, 2000.
45. D'Amico AV, Schultz D, Silver B, et al: The clinical utility of the percent
of positive prostate biopsies in predicting biochemical outcome following external-beam radiation therapy for patients with clinically localized prostate cancer.
Int J Radiat Oncol Biol Phys 49:679-84, 2001.
46. Grossfeld GD, Chang JJ, Broering JM, et al: Under staging and under grading in a contemporary series of patients undergoing radical prostatectomy: results from the Cancer of the Prostate Strategic Urologic Research Endeavor
database. J Urol 165:851-6, 2001.
47. Huland H, Hammerer P, Henke RP, et al: Preoperative prediction of tumor
heterogeneity and recurrence after radical prostatectomy for localized prostatic
carcinoma with digital rectal, examination prostate specific antigen and the
results of 6 systematic biopsies. J Urol 155:1344-7, 1996.
48. Peller PA, Young DC, Marmaduke DP, et al: Sextant prostate biopsies. A
histopathologic correlation with radical prostatectomy specimens. Cancer
75:530-8, 1995.
49. Ravery V, Boccon-Gibod LA, Dauge-Geffroy MC, et al: Systematic biopsies accurately predict extracapsular extension of prostate cancer and persistent/recurrent detectable PSA after radical prostatectomy. Urology 44:371-6,
1994.
50. Ravery V, Boccon-Gibod LA, Dauge-Geffroy MC, et al: [Role of biological and anatomo-pathologic criteria in the prognosis evaluation of patients before and after radical prostatectomy]. Prog Urol 4:673-82, 1994.
51. Wills ML, Sauvageot J, Partin AW, et al: Ability of sextant biopsies to
predict radical prostatectomy stage. Urology 51:759-64, 1998.
52. Ahlgren G, Lindholm K, Falkmer U, et al: A DNA cytometric proliferation
index improves the value of the DNA ploidy pattern as a prognosticating tool in
patients with carcinoma of the prostate. Urology 50:379-84, 1997.
53. Badalament RA, O'Toole RV, Young DC, et al: DNA ploidy and prostatespecific antigen as prognostic factors in clinically resectable prostate cancer.
Cancer 67:3014-23, 1991.
54. Carmichael MJ, Veltri RW, Partin AW, et al: Deoxyribonucleic acid ploidy
analysis as a predictor of recurrence following radical prostatectomy for stage
T2 disease. J Urol 153:1015-9, 1995.
55. Currin SM, Lee SE, Walther PJ: Flow cytometric analysis of comedocarcinoma of the prostate: an uncommon histopathological variant of prostatic adenocarcinoma. J Urol 140:96-100, 1988.
56. Erbersdobler A, Hammerer P, Huland H, et al: Numerical chromosomal
aberrations in transition-zone carcinomas of the prostate. J Urol 158:1594-8,
1997.
57. Forsslund G, Esposti PL, Nilsson B, et al: The prognostic significance of
nuclear DNA content in prostatic carcinoma. Cancer 69:1432-9, 1992.
58. Gauwitz MD, Pollack A, el-Naggar AK, et al: The prognostic significance
of DNA ploidy in clinically localized prostate cancer treated with radiation
therapy. Int J Radiat Oncol Biol Phys 28:821-8, 1994.
59. Greene DR, Rogers E, Wessels EC, et al: Some small prostate cancers are
nondiploid by nuclear image analysis: correlation of deoxyribonucleic acid
ploidy status and pathological features. J Urol 151:1301-7, 1994.
60. Greene DR, Wheeler TM: Clinical relevance of the individual prostate
cancer focus. Cancer Invest 12:425-37, 1994.
61. Hawkins CA, Bergstralh EJ, Lieber MM, et al: Influence of DNA ploidy
and adjuvant treatment on progression and survival in patients with pathologic
stage T3 (PT3) prostate cancer after radical retropubic prostatectomy. Urology
46:356-64, 1995.
62. Henke RP, Hammerer P, Graefen M, et al: Interphase cytogenetic study of
preoperative core biopsies for the prediction of early serum prostate specific
antigen recurrence after radical prostatectomy of clinically localized prostate
carcinoma. Cancer 83:977-88, 1998.
63. Hussain MH, Powell I, Zaki N, et al: Flow cytometric DNA analysis of
fresh prostatic resections. Correlation with conventional prognostic parameters
in patients with prostate cancer. Cancer 72:3012-9, 1993.
64. Khoo VS, Pollack A, Cowen D, et al: Relationship of Ki-67 labeling index
to DNA-ploidy, S-phase fraction, and outcome in prostate cancer treated with
radiotherapy. Prostate 41:166-72, 1999.
65. Lee SE, Currin SM, Paulson DF, et al: Flow cytometric determination of
ploidy in prostatic adenocarcinoma: a comparison with seminal vesicle involvement and histopathological grading as a predictor of clinical recurrence. J
Urol 140:769-74, 1988.
66. Lerner SE, Blute ML, Bergstralh EJ, et al: Analysis of risk factors for progression in patients with pathologically confined prostate cancers after radical
retropubic prostatectomy. J Urol 156:137-43, 1996.
67. Lerner SE, Blute ML, Zincke H: Risk factors for progression in patients
with prostate cancer treated with radical prostatectomy. Semin Urol Oncol
14:12-20; discussion 21, 1996.
68. Miller J, Horsfall DJ, Marshall VR, et al: The prognostic value of deoxyribonucleic acid flow cytometric analysis in stage D2 prostatic carcinoma. J Urol
145:1192-6, 1991.
69. Phillips JL, Hayward SW, Wang Y, et al: The consequences of chromosomal aneuploidy on gene expression profiles in a cell line model for prostate
carcinogenesis. Cancer Res 61:8143-9, 2001.
70. Pollack A, Zagars GK, el-Naggar AK, et al: Near-diploidy: a new prognostic factor for clinically localized prostate cancer treated with external beam
radiation therapy. Cancer 73:1895-903, 1994.
71. Pollack A, Zagars GK, el-Naggar AK, et al: Relationship of tumor DNAploidy to serum prostate-specific antigen doubling time after radiotherapy for
prostate cancer. Urology 44:711-8, 1994.
72. Ross JS, Figge H, Bui HX, et al: Prediction of pathologic stage and postprostatectomy disease recurrence by DNA ploidy analysis of initial needle biopsy specimens of prostate cancer. Cancer 74:2811-8, 1994.
73. Ross JS, Figge HL, Bui HX, et al: E-cadherin expression in prostatic carcinoma biopsies: correlation with tumor grade, DNA content, pathologic stage,
and clinical outcome. Mod Pathol 7:835-41, 1994.
74. Scrivner DL, Meyer JS, Rujanavech N, et al: Cell kinetics by bromodeoxyuridine labeling and deoxyribonucleic acid ploidy in prostatic carcinoma needle
biopsies. J Urol 146:1034-9, 1991.
75. Shankey TV, Jin JK, Dougherty S, et al: DNA ploidy and proliferation
heterogeneity in human prostate cancers. Cytometry 21:30-9, 1995.
76. Song J, Cheng WS, Cupps RE, et al: Nuclear deoxyribonucleic acid content
measured by static cytometry: important prognostic association for patients with
clinically localized prostate carcinoma treated by external beam radiotherapy. J
Urol 147:794-7, 1992.
77. Stege R, Tribukait B, Lundh B, et al: Quantitative estimation of tissue
prostate specific antigen, deoxyribonucleic acid ploidy and cytological grade in
fine needle aspiration biopsies for prognosis of hormonally treated prostatic
carcinoma. J Urol 148:833-7, 1992.
78. Tinari N, Natoli C, Angelucci D, et al: DNA and S-phase fraction analysis
by flow cytometry in prostate cancer. Clinicopathologic implications. Cancer
71:1289-96, 1993.
79. van den Ouden D, Tribukait B, Blom JH, et al: Deoxyribonucleic acid
ploidy of core biopsies and metastatic lymph nodes of prostate cancer patients:
impact on time to progression. The European Organization for Research and
Treatment of Cancer Genitourinary Group. J Urol 150:400-6, 1993.
80. van der Poel HG, Oosterhof GO, Schaafsma HE, et al: Intratumoral nuclear
morphologic heterogeneity in prostate cancer. Urology 49:652-7, 1997.
81. Berruti A, Dogliotti L, Bitossi R, et al: Incidence of skeletal complications
in patients with bone metastatic prostate cancer and hormone refractory disease:
predictive role of bone resorption and formation markers evaluated at baseline. J
Urol 164:1248-53, 2000.
82. Koga H, Naito S, Koto S, et al: Use of bone turnover marker, pyridinoline
cross-linked carboxyterminal telopeptide of type I collagen (ICTP), in the assessment and monitoring of bone metastasis in prostate cancer. Prostate 39:1-7,
1999.
83. Takeuchi S, Arai K, Saitoh H, et al: Urinary pyridinoline and deoxypyridinoline as potential markers of bone metastasis in patients with prostate cancer. J
Urol 156:1691-5, 1996.
84. Smith MR, McGovern FJ, Fallon MA, et al: Low bone mineral density in
hormone-naive men with prostate carcinoma. Cancer 91:2238-45, 2001.
85. Schatzl G, Madersbacher S, Thurridl T, et al: High-grade prostate cancer is
associated with low serum testosterone levels. Prostate 47:52-8, 2001.
86. Hoffman MA, De Wolf WC, A M: Is low serum free testosterone a marker
for high-grade prostate cancer? J Urol 163:824-7, 2000.
87. Dattoli M, Wallner K, True L, et al: Prognostic role of serum prostatic acid
phosphatase for 103Pd-based radiation for prostatic carcinoma. Int J Radiat
Oncol Biol Phys 45:853-6, 1999.
88. Moul JW, Connelly RR, Perahia B, et al: The contemporary value of pretreatment prostatic acid phosphatase to predict pathological stage and recurrence
in radical prostatectomy cases. J Urol 159:935-40, 1998.
89. Han M, Piantadosi S, Zahurak ML, et al: Serum acid phosphatase level and
biochemical recurrence following radical prostatectomy for men with clinically
localized prostate cancer. Urology 57:707-11, 2001.
90. Roy AV, Brower ME, Hayden JE: Sodium thymolphthalein monophosphate: A new acid phosphatase substrate with greater specificity for the prostatic
enzyme in serum. Clin Chem 17:1093-1102, 1971.
91. Batuello JT, Gamito EJ, Crawford ED, et al: Artificial neural network
model for the assessment of lymph node spread in patients with clinically localized prostate cancer. Urology 57:481-5, 2001.
92. Han M, Snow PB, Epstein JI, et al: A neural network predicts progression
for men with Gleason score 3+4 versus 4+3 tumors after radical prostatectomy.
Urology 56:994-9, 2000.
93. Bostwick DG, Burke HB: Prediction of individual patient outcome in cancer: comparison of artificial neural networks and Kaplan--Meier methods. Cancer 91:1643-6, 2001.
94. Babaian RJ, Fritsche H, Ayala A, et al: Performance of a neural network in
detecting prostate cancer in the prostate-specific antigen reflex range of 2.5 to
4.0 ng/mL. Urology 56:1000-6, 2000.
95. Partin AW, Yoo J, Carter HB, et al: The use of prostate specific antigen,
clinical stage and Gleason score to predict pathological stage in men with localized prostate cancer. J Urol 150:110-4, 1993.
96. Partin AW, Kattan MW, Subong EN, et al: Combination of prostatespecific antigen, clinical stage, and Gleason score to predict pathological stage
of localized prostate cancer. A multi-institutional update. JAMA 277:1445-51,
1997.
97. Partin AW, Mangold LA, Lamm DM, et al: Contemporary update of prostate cancer staging nomograms (Partin Tables) for the new millennium. Urology
58:843-8, 2001.
EARLY HORMONAL THERAPY WORKS
RIDICULOUSLY WELL
By Robert Leibowitz, M.D. and Steven Tucker, M.D.
Compassionate Oncology Medical Group
Los Angeles, CA
310/229-3555
Traditionally, patients with prostate cancer were offered only three treatment options: observation (no
treatment), radical prostatectomy (the alleged gold
standard), and standard radiation therapy. A fourth
treatment option, brachytherapy or seeds, has been
increasingly offered. Since 1991, the only treatment
we have recommended is primary androgen deprivation therapy without any radical local treatment. We
call triple hormone blockade® the “Platinum and
Diamond Standard,” because we believe it is far superior to any “gold standard.”
At the European Oncology Conference, September
22, 2003, Abstract 328 was presented and discussed.
In a press conference held afterwards, Sir Richard
Peto, Ph.D., Professor of Medicine Statistics at the
University of Oxford, United Kingdom, was interviewed. Dr. Peto has gained international recognition
and fame with his analysis of the adjuvant therapy for
breast cancer (this refers to treatment given after surgery or radiation therapy to reduce the risk of cancer
recurrence). We believe the following statement best
describes Dr. Peto’s analysis. “Hormonal therapy as a
whole works ridiculously well.” Significant reductions in ten-year mortality rates have been identified
in the United States and United Kingdom, as well as
elsewhere in Europe. A meta analysis is a type of
analysis that pools the results from all pertinent
medical publications, hoping that by adding together
all of the patients in each trial, it is more likely that
you will identify statistically significant conclusions
because of the larger sample size. Dr. Peto looked at
early versus late initiation of hormonal therapy. His
meta analysis concluded that early hormone blockade
for prostate cancer is about as effective as it is for
early breast cancer....” When asked why so many
physicians are reluctant to prescribe early hormonal
therapy when the survival benefits are so great, Dr.
Peto primarily attributed this to tradition. I would
interpret that as reluctance on the part of physicians
to open their (sometimes closed) minds to change and
allow themselves to learn about new and effective
treatment options. “Meta analysis provides strong
evidence of benefit, and when you add them (the
studies) all together, they are very clear, showing improved prostate mortality....” Early use of hormone
blockade reduced the probability that you would die
from prostate cancer in the next ten years by about
one-third, and all other deaths were not increased.
A very well known and internationally respected
urologist, Dr. E. David Crawford, Professor of
Urologic Oncology at the University of Colorado
Health Sciences Center in Denver, in a telephone interview, stated “Early hormonal therapy saves lives,
and can even be considered to be a cure of prostate
cancer.” Although not involved in this study, he
states, “We have been on this bandwagon for years.
When I give a talk on this, I like to start by asking for
a show of hands on how many people think early hormonal therapy can be a cure for prostate cancer. I
do.” (Dr. Bob has never claimed early hormone
blockade could cure prostate cancer, but he loved
discovering that Dr. Crawford believes it can.) Dr.
Crawford went on to state that “early signs of a drop
in prostate cancer mortality in the 1990's could not
have been accounted for by improved screening and
detection with PSA testing because the test was too
new to have an impact on death rates. At least some
of the decline was likely attributable to the inhibition
of cancer growth by hormone blockade.” Dr. Bob
comments, “It is known that 80% of men in their 80's
have prostate cancer, but only 2 - 3% of men die
from prostate cancer. Most of us will die with prostate cancer; not from it. Therefore, for most men, it
is not necessary to be cured of prostate cancer in order to enjoy a normal life span.” Treatment with 13
months of triple hormone blockade/Leibowitz protocolВ® is the least invasive treatment option for socalled localized prostate cancer, but still is a most
potent and effective form of therapy. It is also the
only non-chemotherapy treatment option that can kill
prostate cancer cells that have escaped from the prostate and spread to places like your bones.
Dr. Crawford had been one of my most vociferous
critics in the past, stating that hormone blockade
could never cure prostate cancer, and that patients
should never consider primary hormone blockade as
a viable treatment option. During a question and answer session following one of his L.A. area lectures,
he literally took one of our patients to task when this
patient asked, “What about using hormone blockade
as sole treatment for so-called, localized prostate
cancer?” Dr. Crawford was extremely indignant and
quite rude, stating categorically that hormone blockade is not an acceptable treatment option; period; end
of discussion. Perhaps Dr. Crawford would be impressed (astonished) if he was told that this patient
continues to remain in a clinical complete remission
for more than six years in spite of the fact that he had
aggressive, negative baseline prognostic factors. His
only treatment was 13 months of triple hormone
blockade/Leibowitz protocolВ®, followed by finasteride maintenance therapyВ®. It is amusing to hear
Dr. Crawford say that “...we’ve been on this bandwagon for years.” He sure wasn’t on this bandwagon
when he lectured in L.A. just a few years ago. However, we welcome company on the primary hormone
blockade as sole therapy for prostate cancer bandwagon. We were the first to advocate this option
more than 12 years ago, and remain a most vociferous spokesperson for this approach.
CAPSURE data was presented at the American
Urologic Association in May 2003, and reported that
from 1989 through 2001, the use of primary androgen
deprivation therapy as a treatment option had risen
sharply. For low-risk patients, the use almost tripled
to 14.2%. For intermediate risk, it more than doubled
to approximately 20%, and for high-risk, it increased
from 33% to 48%. Almost one-half of men with
high-risk disease selected hormone blockade as their
treatment option. They investigated and discovered
how poor the results were from any form of radical
local therapy. Obviously, more and more doctors are
either prescribing or agreeing to prescribe hormone
blockade as the first and only treatment for prostate
cancer patients. High risk is defined as a PSA equal
to or greater than 20, or a Gleason score of 8-10, or
locally advanced disease. Low risk is a PSA less
than 10, a Gleason score of 6 or less, and nonpalpable
or only a small abnormal area identified on digital
rectal exam. Intermediate risk includes everyone
else.
It seems ironic that when surgery or radiation therapy
fails to control your prostate cancer, then your urologist or radiation therapist will inevitably prescribe the
same type of hormone blockade that we prescribe
initially. Why subject yourself to radical local therapies with the well-known, often permanent complications of erectile dysfunction (impotence) and urinary
incontinence? One-third of men report they use a
pad, diaper, or penile clamp after radical prostatectomy. More than 60% report that they drip urine.
Eighty-five percent report the inability to achieve and
maintain an erection firm enough to allow for intercourse. Seven percent suffer from fecal incontinence.
Imagine how you would feel if you developed one or
more of these complications, but in spite of this you
later required treatment with hormone blockade because of a rising PSA? Skip the radical local therapies and start with triple hormone blockade/Leibowitz protocolВ®.
We firmly believe that you never save your best prostate cancer treatment for later. The time to kill prostate cancer cells is now. Do not allow prostate cancer
cells the opportunity to mutate and become more aggressive. If any therapy works well in more advanced disease, it essentially always works much
better in earlier stage disease. Hence, give your
hormone blockade early rather than late. When radical prostatectomy or radiation therapy fails to cure a
man, the PSA doubling time shortens from three to
four years pre-surgery or pre-radiation, to about four
months after those treatments. Frightening, but true.
Remember, no study has ever shown any form of
radical local therapy to be both necessary and effective.
Dr. Fernand Labrie reported in the early 1990's that
for men who presented with one to five separate metastases identified on bone scan, their median survival was greater than eight years. These men didn’t
have bone cancer; they had prostate cancer cells in
their bones. Hormone blockade can kill prostate cancer cells in your prostate, lymph nodes, and bones as
well.
Patients with obvious metastatic disease to bones
have much shorter survival than patients with normal
bone scans, even though a normal bone scan does not
exclude the possibility that occult metastatic disease
exists. More than 10 - 15% of a bone must be dissolved before a bone scan is abnormal. It takes destruction of 40% or more of a bone before an x-ray
becomes abnormal. There can be billions of cancer
cells, with a normal bone scan. Men with abnormal
bone scans have much more aggressive disease.
Their prostate cancer cells have figured out a way to
escape from the prostate, survive in the circulation,
leave the circulation, “nest” in bones, attract blood
supply to them, and develop successful colonies or
islands of metastatic cells. Only the most aggressive
cells are able to accomplish all of these steps. It is
reassuring that even in men with up to five identified
metastatic deposits on bone scan, eight years after
starting hormone blockade, more than half were still
alive in the Labrie study. Dr. Labrie used continuous
double hormone blockade.
We are confident that intermittent androgen blockade
is far superior to continuous blockade. We are also
convinced that triple hormone blockade/Leibowitz
protocolВ® is the most effective form of hormone
blockade, and is much better than double blockade.
We feel the best results are obtained using a single
13-month cycle of triple hormone blockadeВ® up
front, rather than intermittent hormone blockade.
Following that first cycle of hormone blockade, use
all of your supportive treatments to avoid the need for
a second cycle of hormone blockade. The longer you
are off hormone blockade, the much longer you will
survive. You cannot get hormone refractory unless
someone puts you back on hormone blockade. Examples of these supportive therapies include finasteride maintenance therapy (a small percent of our
patients take dutasteride [Avodart]). All of our patients are on either one or the other. Virtually all take
a COX-2 inhibitor, preferably Celebrex. The other
COX-2 inhibitors we sometimes use are Vioxx or
Bextra. Calcitriol and/or PEENUTS may have some
limited beneficial effects. We have found that thalidomide is the most successful treatment option that
helps to postpone or avoid the need for another cycle
of hormone blockade. In our experience, more than
85% of men will respond to thalidomide by showing
a decline in PSA, usually within weeks of starting
therapy. You can request a videotaped lecture that
discusses and explains how to avoid getting hormone
resistant or refractory. Request Video #2 which is a
lecture given in August 2001.
Dr. Labrie’s survival figures are from a 1992 report.
These survival statistics occurred in the era before we
identified modern, effective therapies that we use for
those men who fail initial hormone blockade. This
information should reassure any patient with low-risk
prognostic factors that almost without exception we
expect them to do well for an indefinite period of
time, well beyond eight years, if they are treated appropriately.
For those men who present with intermediate-risk
factors, the protocol described below also confirms
their excellent prognosis. The men who present with
one or more high-risk factors almost always require
treatment with 12 doses of mild, easily tolerated,
low-dose chemotherapy in addition to 13 months triple hormone blockade/Leibowitz protocolВ®. None of
these patients develop nausea or vomiting; hair loss is
rare; most working men continue to work full time
during therapy.
Men are amazed at how nontoxic this treatment is,
and how well it is tolerated. We have a list of volunteers who have been treated with this protocol and are
happy to discuss this treatment with you. Video #4
from October 2002 has additional helpful information.
Triple hormone blockade/Leibowitz protocolВ® refers
to men who have never had any form of local therapy
and have never had any form of prior hormone
blockade. These men are treated with 13 months of
triple hormone blockadeВ® utilizing Lupron or
Zoladex, three Casodex per day, and one finasteride
(Proscar) per day. After 13 months, they are treated
with finasteride maintenanceВ® (Proscar maintenance
therapy). For men who cannot afford three Casodex
per day, we recommend Eulexin, 250 mg three times
per day. We do not recommend using one or two
Casodex per day. You need three for optimal results.
You can request a copy of a videotaped lecture given
by me [Dr. Leibowitz (some of my lectures are also
available in DVD)] to further explain in detail this
information regarding triple hormone blockadeВ®. A
July 2001 lecture also describes all of the choices for
local therapy as well as the side effects from each
form of treatment. A lecture from May 2003 updates
our triple hormone blockade/Leibowitz protocolВ®
results, and may convince you to consider treatment
with high-dose testosterone replacement therapy after
your triple hormone blockadeВ® has been completed.
The February 2002 lecture addresses subjects including our antiangiogenic cocktail; high-dose testosterone replacement therapy; as well as different approaches for achieving optimal management of all
stages of prostate cancer. Call our office for a description of these lectures. Dr. Tucker has taped a
lecture given in San Diego in October 2003. A copy
of that lecture is also available.
In September 2003, I (Dr. Leibowitz) presented our
updated data at the Prostate Cancer Research Institute
Symposium. I reported on 177 men, all with biopsyconfirmed prostate cancer. All men refused local
therapy; all men were treated in a single practice, by
myself or Dr. Steven Tucker. Their average age is
66. Their average baseline PSA is 11.5. Their median Gleason grade is 7. We had 71 patients with a
Gleason 7; 24 with a 4+3, and 47 with a 3+4.
Twenty-one of our men had Gleason scores of 8 to
10, and 85 had a Gleason score of 4 to 6, with a rare
4 or 5. The largest percentage of our patients were
stage T1c or T2a; however, at least 20% were locally
advanced. The first 134 men treated have a mean
follow-up of 60 months. Their current mean PSA is
2.49. Ninety patients have been followed for a mean
of six years, and their mean PSA is 2.8. Almost 50
men have been followed for a mean of seven years;
their mean PSA is 2.678. Baseline testosterone was
388; on finasteride maintenanceВ® 530. Finasteride
(or Proscar) raises your testosterone level.
Through September 2003, we have only had to retreat 12 men. All 12 of these patients presented with
at least one high-risk prognostic factor.
As of September 2003, our disease specific survival
is 99.4%. This means that only one patient in 177
died from prostate cancer. These results are superior
to any reported surgical or radiation therapy series.
Our results were published in the journal, The Oncologist, an international, peer-reviewed journal; see
“Treatment of Localized Prostate Cancer with Triple
Androgen Blockade: Preliminary Results in 110
Consecutive Patients;” 2001; 6:177-182. Our article
was referenced at the 2003 AUA convention in a
course on androgen deprivation therapy. The syllabus, written by Dr. Eric Small, reads “Triple androgen blockade employing simultaneous LH-RH agonist, antiandrogen, and 5-alpha-reductase inhibitor
(finasteride) may offer additional benefit over stan-
dard double hormone blockade, particularly in the
context of intermittent treatment protocols.” Our
work was also referenced in the Journal Cancer, published by the American Cancer Society.
It is immensely satisfying to me (Dr. Leibowitz) personally that my work utilizing triple hormone blockadeВ® with finasteride maintenance therapyВ® has
been so successful, is finally being recognized, and is
increasingly accepted as an appropriate primary
treatment option. Being the first to name and pioneer
this approach that offers men a treatment option
without incontinence and is the only treatment option
whose side effects are almost always reversible,
makes me proud and happy. Mayoclinic.com agrees
that one of the treatment options commonly used by
men with (so-called) localized prostate cancer is
hormone blockade. This is your Fifth Treatment Option. We believe that our results confirm our opinion
that triple hormone blockade/Leibowitz protocolВ® is
the best treatment option (hence the name, The Platinum and Diamond Standard). It avoids any form of
radical local therapy. Why take the risk you might
need a diaper, pad, or (God forbid) penile clamp?
Avoid the possibility of fecal incontinence or soiling.
About one-quarter to one-third of men, after being
treated with radiation therapy, report moderate to severe gastrointestinal complications including bleeding or fecal soilage after radiation therapy. Following radiation therapy, approximately 85% of men develop erectile dysfunction within four years of treatment. Erectile dysfunction was defined as inability to
get and maintain an erection firm enough for intercourse.
Start your treatment with triple hormone blockade/Leibowitz protocolВ®. This buys you the time
needed to investigate all other options. Later, if you
decide, you can add local therapy. You are not burning any bridges by starting with triple hormone
blockade®. We don’t recommend local therapy, but
you have the option to add it at any time. Currently,
about two-thirds of men treated with radiation therapy for locally advanced prostate cancer are told that
they also need to take hormone blockade. No study
has ever shown that radiation therapy adds to the
benefit of hormone blockade. Prospective randomized trials have proven that radiation therapy plus
hormone blockade statistically prolongs survival
compared to radiation therapy alone. After all of
these years, no study has shown an advantage from
adding radiation therapy to hormone blockade. The
value of using hormone blockade is proven. This is
not just our opinion; this is proven medical fact.
Simply stated, we do not believe in any form of radical local therapy. Seventy-three percent of men,
prior to the start of their radical prostatectomy surgery, already have PSA-secreting cells in their bones
(bone marrow). Most experts agree that these are
malignant prostate cancer cells. Not all will grow
into mature metastases, but it is sobering to realize
that three out of four men have these cells in their
bones at diagnosis. This is one of the major reasons
we believe prostate cancer is a systemic disease.
This means that prostate cancer cells have already
spread to lymph nodes and/or bones by the time you
are first diagnosed. Since triple hormone blockade/Leibowitz protocolВ® is systemic therapy, it can
attack prostate cancer cells anywhere and everywhere
in the body. No form of local therapy kills the prostate cancer cells that have already spread to your
bones or other distant sites. Dr. Peto, after analyzing
the world’s literature, concludes how ridiculously
well hormone blockade works. Dr. Crawford has
admitted (? confessed) that hormone blockade kills
prostate cancer cells. Let triple hormone blockade/Leibowitz protocolВ® help you, too.
We have a very long list of patients who were treated
with our triple hormone blockade/Leibowitz protocolВ® and now volunteer to answer any questions or
concerns that you or your significant other may have.
Please call our office for a copy of that list. Call
them and hear what they have to say.
Note:
Triple hormone blockade® is Dr. Bob’s registered trademark.
Triple androgen blockade® is Dr. Bob’s registered trademark.
Finasteride maintenance therapy® is Dr. Bob’s registered trademark.
WHAT THE HECK HAS BEEN GOING ON IN
MY WORLD - Part IV!!!
By Mark A. Moyad, M.P.H.
By Mark Anthony (yes I do know that there was a
famous Roman emperor that was very intelligent and
good looking and good-hearted and he was from
Rome, but I share no similarities to that guy except
for the good looking, good hearted and kind part but I
am not from Rome) Moyad, M.P.H. (also keep in
mind that this is the last PAACT issue that will show
my M.P.H. alone credentials cause in the next issue it
will say M.D., M.P.H. - yes I am graduating in June
after 9 years which means I hope that you keep your
graduation gifts to me under 1000 dollars for the
most part - oh by the way I really like that George
Foreman grill and I need a new washer and dryer and
car if you get my drift….).
FIRST THE REALLY GOOD NEWS BUT THIS
IS A WARNING THAT THIS IS A SHAMELESS
PROMOTION THAT I HAVE BEEN WAITING
5 YEARS TO DO! (PRETTY DRAMATIC
SOUNDING DON’T YOU THINK BUT TRUE!!!)
Here we go again. Buckle up because we have a lot
to cover in this issue. First let’s start with my
SHAMELESSS PROMOTION NUMBER 3063. I
have been asked by some people what happened to
my newsletter or journal and why we still do not publish it and my answer was that it was too much work
for a staff of 1 or 2 people - we simply underestimated the response, but if a legitimate company
wanted to help us I would continue to do the newsletter/journal. Well, the good news is that it is now official. One of the largest medical publishers in the
world has decided to publish a version of this journal
4 times a year along with providing internet access to
other articles, medical meetings, new drugs and supplements. We will also spend a heck of a lot of time
telling you what not only seems to work, but what
also seems to be worthless! I am happy to report that
after 5 years we finally have a company that will
handle the journal and the first issue will be published in the late fall of 2004. This journal will review articles in conventional and alternative medicine for chronic diseases from A-Z. In other words,
from arthritis to breast cancer, cardiovascular disease
to colon cancer, diabetes to osteoporosis to prostate
cancer to erectile dysfunction to menopause to hot
flashes to skin cancer to any of the chronic diseases… it will simply keep you up-to-date every 3
months of what has occurred in the previous 3
months in these and other areas of medicine. Also,
although I will be doing most of the writing in each
issue - about 33% or more of each issue will be written by numerous objective researchers from around
the world. For example, in the first issue we have a
respected researcher from Harvard writing about cardiovascular disease, and a respected researcher from
San Diego writing about prostate cancer… Also, I
wanted to make sure that it was cheap and at the
same time if you are interested in subscribing that
your name and address are protected. In other words,
I did not want you to receive 40 pieces of mail from
this and other companies after you expressed interest
in this journal. Therefore, the other guarantee that
was made by the medical publisher is that by contacting or e-mailing the publisher and letting them know
that you are interested in the journal Seminars in
Preventive and Alternative Medicine (keep in mind
that we will be talking about a lot more than just prevention of a disease but also preventing recurrence of
a disease or preventing side effects…) that you would
be protected. Therefore, if you are interested in subscribing - contact Catherine Bewick at Elsevier publishing in Philadelphia and leave a message with your
name, phone number, address and express your interest in the Moyad journal called “Seminars in Preventive and Alternative Medicine” Or you can send an email message. This is only to express interest and in
the next month or two they will contact you and discuss further if you are still interested in subscribing
after hearing more about the prices and the journal
itself. Catherine Bewick’s number is 215-238-7877
Her e-mail is c.bewick@elsevier.com. I REALLY
HOPE YOU WILL INQUIRE ABOUT THIS
JOURNAL BECAUSE I THINK IT WILL BE
WORTH IT FOR ANY MAN OR WOMAN.
THANKS FOR LETTING ME STAND ON MY
COMMERCIAL SOAP-BOX FOR A MINUTE.
20) LET ME GET THIS STRAIGHT (PUN
INTENDED) - EJACULATIONS ARE GOOD
FOR ME AND MAY ACTUALLY REDUCE
THE RISK OF PROSTATE CANCER??
There is an old philosophy in medicine known as the
“use it or lose it theory.” In other words, exercising
certain parts of the body can reduce your risk of certain conditions. For example, it seems that reading a
lot or exercising the brain may reduce the risk of dementia or memory problems. Exercising the heart
may reduce your risk of heart disease. Lifting
weights can increase the size of your muscles and
reduce the risk of osteoporosis. Therefore, researchers decided to look at the risk of prostate cancer in
those men that exercise the prostate or men that have
frequent ejaculations. Researchers from the Health
Professionals Follow-up Study decided to analyze
data on 29,342 U.S. men aged 46 to 81 years that
provided information on the history of ejaculation
frequency in 1992 and every 2 years until the year
2000. Interestingly, a high ejaculation frequency was
associated with a reduced risk of total prostate cancer! There was an 11% decreased risk of prostate
cancer in men reporting 21 or more ejaculations per
month versus men reporting 4-7 ejaculations per
month at the ages of 20 to 29 years, a 32% reduction
in men ages 40 to 49 years, a 51% reduction in men
reporting the highest number of ejaculations in the
year before the final analysis, and a 33% reduction
over an entire lifetime. In other words, more ejaculations were associated with a reduced risk of prostate
cancer. Again, the reduction in risk was for the men
that reported 21 or more ejaculations per MONTH
compared to men reporting 4-7 ejaculations per
month. My gosh - 21 or more ejaculations per
month!!! I get tired and sleepy just reporting this
data!
Researchers are not sure that having a lot of ejaculations after a prostate cancer diagnosis actually can
help or hurt, but I have to think that it is not necessarily a bad thing. However, be careful in how you report this data to your spouse, because some men may
be insensitive and report to their wives that unless
they have more ejaculations it is their spouses who
are putting them at an increased risk of prostate cancer. Regardless, I am just the researcher here reporting the data and it seems that ejaculations are a good
thing after all. Oh and that urban legend is not true
that more self-ejaculations can lead to blindness!
That is ridiculous but that was what my parents told
me when my hormones were kicking in as a teenagar
(whoops I spelled that wrong because I have trouble
reading the keyboard on my computer. What I meant
to type in there was the word “teenager” - anyone
seen my glasses?). Finally, there is a rumor that a
researcher in the future is going to find in a study that
being more romantic and loving to your wife and
providing her with expensive new jewelry every 4-6
months may reduce the risk of breast cancer or just
asking for directions (if you are a man) while driving
in the car with your wife when you get lost can reduce the risk of breast cancer or letting your wife use
the TV. remote control once in a while can reduce
the risk of breast cancer or…. (Reference: Leitzmann MF, et al. JAMA 2004;291:1578-1586).
21) CAN EATING FISH REDUCE MY RISK OF
PROSTATE CANCER RECURRENCE???
This data comes from the same study as the one referenced above (the Health Professionals Follow-up
Study). However, 51,529 men were involved in this
part of the study. There were 675 prostate cancer
cases that had completed post-diagnosis follow-up
data. A total of 171 cases of prostate cancer recurrence cases were reported. Interestingly, a greater
post-diagnostic intake of fish was associated with a
significant 27% reduction in the risk of prostate cancer recurrence. Therefore, eating more fish in your
diet may not only reduce the risk of prostate cancer,
but the risk of prostate cancer returning in men already treated for prostate cancer. The bottom line is
that eating fish is a heart-healthy lifestyle addition,
and in the worst case scenario may reduce the risk of
sudden cardiac death or heart disease. So, why not
eat more fish??? Well, some individuals are concerned about the mercury levels in fish. In addition,
the FDA has warned that large predatory fish, especially shark, tilefish, king mackerel, and swordfish
may contain high levels of mercury. Now, I do not
remember the last time I asked my waiter or waitress
for shark or tilefish, but I am not worried about our
fish supply overall. It is important to remember that
baking, broiling, or even raw fish (yes - sushi) can be
healthy but fried fish is not healthy (sorry you Filet O
FishВ® lovers out there). Also, we are not sure if fish
oil capsules can also impact the risk of prostate cancer or the recurrence of this disease, but fish oil supplements have been shown to reduce the risk of sudden cardiac death in individuals at high risk for such
an event. Several large heart disease organizations
now recommend fish oil capsules for patients with a
high-risk of a cardiovascular event. Fish oil supplements are also low in mercury because they mostly
come from the small fish that contain less mercury.
If you are interested in taking fish oil supplements
please talk to your doctor. Fish oil supplements contain 2 compounds known as “EPA” and “DHA.”
These 2 compounds are omega-3 fatty acids or heart
healthy compounds. They can reduce triglyceride (a
potential blood marker for heart disease that is a part
of the fasting cholesterol blood test) levels in individuals with abnormally high levels of triglycerides.
Past studies of fish oil have shown that about 1 gram
a day of EPA + DHA may have the biggest benefit
with the lowest rate of side effects. Again, talk with
your doctor first because fish oil pills can thin your
blood too much, especially when combined with
other blood thinners like aspirin, coumadin … (obviously, it is best to first increase your consumption of
dietary fish). Also, numerous companies now have
enteric-coated fish oil supplements which significantly reduce the risk of having a bad fishy after-
taste, so ask your doctor about these supplements.
However, one big problem with supplements as you
may or may not know is that there is no guarantee of
quality-control. In other words, how can you be sure
that what you are buying is actually in the supplement bottle? One way to do this is to log on to
www.consumerlabs.com and they have a list of potential supplements that have quality-control because
they were tested. Approximately once a week, I log
on to consumerlabs.com to check the quality control
of a variety of supplements and I think it would be
wise for you to check it once in a while.
Anyhow, I got off track here, but this finding from
this recent study is very interesting and it could be
that eating fish several times a week including tuna
fish in a can in water or salmon… could reduce the
risk of prostate cancer recurrence after treatment of
prostate cancer. Regardless, let’s look at this in a
different way. Let’s just say or pretend that researchers 10 years from now clearly find that fish does not
reduce the risk of prostate cancer recurrence. Who
gives a “______________” (insert bad word in that
previous spot). What I love about fish is that it can or
may:
1) Reduce your risk of sudden cardiac death
2) Reduce your risk of arthritis and other chronic
conditions
3) Provide a large source of vitamin D
4) Provide a large source of selenium
5) Reduce the risk of depression…
The point is that fish consumption has already demonstrated numerous potential health benefits and that
is why it just makes sense to consume more of this
stuff. We are not sure if shellfish have the same potential impact, but we will keep you up-to-date and
who gives a _________ anyway! Shellfish just taste
good and have omega-3 fatty acids, so VIVA LA
SHELLFISH!!! (Reference: American Urological
Association Annual Meeting 2004; page 117, abstract
#442).
22) CAN DUTASTERIDE (AVODARTВ®)
REDUCE THE RISK OF PROSTATE CANCER
IN
MEN
WITH
BPH
(PROSTATE
ENLARGEMENT OR BENIGN PROSTATIC
HYPERPLASIA)?
We already know that taking dutasteride at 0.5
mg/day may reduce the symptoms of BPH. This
dose reduces the blood levels of DHT (the more po-
tent form of testosterone) by more than 93%. It
seems that from previous BPH studies the use of 0.5
mg/day may reduce the risk of prostate cancer. This
is now being tested more accurately in a large randomized trial. In the meantime, please continue to
ask your doctor about the potential benefits and detriments of taking finasteride (ProscarВ®) or dutasteride (AvodartВ®) for BPH or after a prostate cancer diagnosis. It could be that these drugs have an
effect, but we still are not sure. Regardless, they initially appear promising but we need more data. Now,
the company that sells dutasteride and the company
that sells finasteride are obviously competitors and
you need to be careful not to get caught up in the
competition. In other words, ask your doctor about
the similarities and the differences between the two
and ask your doctor if he/she gets paid by either
company to do some speaking or to be an advisor…
In other words, is there a conflict of interest? For
example, one big difference between finasteride and
dutasteride is their half-life or how long the drug is
still active in the body. Dutasteride has a half-life of
several weeks which means it is probably active for
longer periods of time and if you miss a few dosages
every week it is probably no big deal, but finasteride
has a shorter effect that does not last as long. Now, if
I worked for the dutasteride company I would probably sell you on the point that our drug works for a
long period of time, which means you can miss a few
dosages or days of taking it here and there and it may
be no big deal and it reduces DHT to a greater degree
so obviously we might be better... However, if I
worked for finasteride and I wanted to sell this drug
to you I would tell you it has been tested much more
in humans and in a cancer prevention study and it has
good safety data and although it does not stay in your
body for a long period of time this is an advantage
because any drug that stays in your body for a long
time can be a problem if you start experiencing side
effects because it will take a long time for it to go
away. Anyhow, you get the point. Try not to get
caught up in the competition between the 2 and if you
are interested, just ask your doctor for an objective
assessment of the 2 drugs.
I just got back from our Annual Urology Meeting in
San Francisco and there were so many studies and so
much attention paid to weight gain and prostate cancer (made the front cover of the USA Today newspaper on May 11, 2004) that I thought it would be appropriate to repeat a section from the last issue of
PAACT plus add a little more to it from the meeting.
So here goes…
23) CAN LOSING WEIGHT OR MAINTAINING
A HEALTHY WEIGHT BEFORE OR AFTER
RADICAL PROSTATECTOMY OR OTHER
TREATMENT BE A BENEFIT FOR ME?
Here we go again and again. I am often asked what
kinds of lifestyle changes or supplements are best
after being diagnosed with prostate cancer. One of
the best answers continues to be that maintaining a
healthy weight is one of the best things that you can
do for yourself. However, this is not an easy thing to
do. Ask your doctor to continually monitor your
body mass index (BMI), which is your weight in
pounds divided by your height in inches squared mul2
tiplied by 704 (pounds/inches x 704). For example,
I am 195 pounds on a good day and I am 6 foot 1
inches tall or 73 inches tall (which was an initially
impressive height when I was asking my future wife
out on a date). Thus, my BMI = 25.8 (my goal is to
get to 25.0 or less - we all need to work on this). The
higher the value the more we become concerned. In
other words, a BMI of 25 to 29 is considered “overweight” and a BMI of 30 or more is considered
“obese.” This is a fast test but it is not a perfect test.
For example, if you have a lot of muscle mass or lift
weights there is a higher chance that your BMI is
falsely elevated (as in my case because I have an incredible Hulk like body, in my dreams mostly). Regardless, BMI is still one of the fastest ways to determine how you are doing, because as the BMI approaches 30 or more it is a good indicator of a potential problem. Another good method I use to monitor
a patient’s weight is by using the WHR or Waist-toHip ratio. This is as simple as it sounds. We measure your waist and hip (waist divided by hip = W/H)
and the larger the number the more we become concerned. There are no magic numbers or cut off values for WHR. I just like to measure a patient’s WHR
and compare his/her recent measurement to his/her
past measurement. Simply put, if your number increases in time this means that your belly or abdominal fat tissue is probably increasing in size and this is
not a good thing.
So, let’s get to the scary recent research, which may
change the way we treat patients being treated for
prostate cancer. Two new studies in the February
issue of the Journal of Clinical Oncology were actually released early by the journal itself. Researchers
(Freedland SJ, et al. & Amling CL, et al. = 2 cool
guys and good researchers) essentially found that out
of 1000s of men being treated for radical prostatectomy there was a significantly increased risk of more
aggressive prostate cancers and biochemical failure
in the more obese men. In other words, it seems that
obesity increases the risk of a man experiencing recurrence after being treated with surgery. The other
scary finding was that the number of obese men having surgery for prostate cancer seems to have doubled
in the last 10 years!!! What should be learned from
these studies??? Men need to continue to discuss
ways of losing weight or maintaining a healthy
weight with their doctor after being diagnosed with
prostate cancer. It is amazing to me that some men
focus on some conflicting data that may suggest that
obesity is slightly protective against getting prostate
cancer. However, this is not the point because
whether or not obesity increases or decreases your
risk of getting prostate cancer is not the issue, because the research strongly suggests that obesity increases the risk of dying earlier from most diseases
and this is the point that needs to be stressed. It is
kind of like arguing whether or not seat belts increase
the risk of bruising your chest in a car accident. The
point is that wearing seat belts saves lives and not
wearing seat belts increases your risk of dying in a
car accident. Do not get overly obsessed at looking
at the tree and forgetting about the forest all around
you. Obesity is not a good thing for you if you have
been diagnosed with prostate cancer. Discussing
ways to reduce weight with your doctor is of primary
importance after a diagnosis of prostate cancer.
Again, I do not want to sit here and preach that it is
easy to lose weight because it is not. In fact, 3500
calories is equal to 1 pound, which means that if you
just cut your overall caloric intake by 500 calories a
day (that is a lot) and do nothing else it takes about a
full week to lose 1 pound!!! Man, that is slow and
not very dramatic so it takes patience and commitment. However, being fit is also of primary importance because we see patients do better if they are fit
first. In other words, do I think a man with a BMI of
30 that exercises 3 times a week and does not lose
weight has a better chance of doing well versus another man with a BMI of 30 that doesn’t exercise at
all??? You bet! Also, keep in mind that the most
recent research from our Annual Meeting suggests
that men with even higher BMIs of 35 or more actually may do even worse than the men with BMIs of
30-34. In other words, the higher the number the
worse things can get for you. Talk to your doctor
about the latest methods to lose weight from diets,
weight watchers®, drugs, surgery…
24) ARE OVER THE COUNTER ERECTILE
DYSFUNCTION DIETARY SUPPLEMENTS
SAFE???
A recent study from our annual urology meeting
comes from a group of Canadian researchers that
really had some scary results. These researchers
found out of several dietary supplements for erectile
dysfunction tested - it turns out that a few contained
high dosages of ViagraВ® and CialisВ® - yes 2 prescription drugs that are used for erectile dysfunction.
In fact, these companies sold dietary supplements
that actually had a lot of prescription drug in the bottle. This is scary because some of these drugs are
already a concern in men who are taking nitrate drugs
or will be given nitrate drugs for heart disease because of the dangerous interaction (remember the recent Jack Nicholson and Diane Keaton movie where
Jack was taking ViagraВ® and the doctor played by
Keeanu Reeves asks Jack if he is taking ViagraВ® because he wanted to give him a nitrate drug for his
heart attack…), and it is a concern in men that are
taking some of the alpha-blocker drugs for BPH because of the potential dangerous interaction or potential large drop in blood pressure. The point is that
you may think you are buying a dietary supplement
without prescription drugs in them, but some companies may secretly place prescription drugs in the bottle or may have herbal compounds that look similar
to a prescription drug (Remember the PC-SPES mess
from last year). Never take a dietary supplement for
erectile dysfunction without first talking to your doctor! It is really that simple. (Reference: Fleshner
NE, et al. American Urological Association Annual
Meeting 2004, page 314, abstract #1190).
25) WHEN IS THE BEST TIME OF YEAR TO
BUG MY DOCTOR ABOUT THE LATEST
CLINICAL
RESEARCH
IN
PROSTATE
CANCER???
This sounds like a strange question but I have an answer to it. Patients need to realize that every year in
May and June two of the largest prostate cancer
meetings for researchers take place and we get a
glimpse of the potential exciting and not so exciting
research that will be published in medical journals in
the next year or two. One meeting is called “The
American Urological Association Annual Meeting or
AUA” and it just took place for a week in San Francisco. The other meeting is called “the American Society of Clinical Oncology Annual Meeting or
ASCO” and it will be held in June in New Orleans,
LA. There are literally hundreds of studies presented
at these meetings in less than a week. Again, the latest research on prostate cancer is presented, so the
best time to either do your own research on these
meetings or to talk to your doctor (because many
doctors attend these meetings) is after the month of
June. Now, of course I do not mean that you should
call the office or your doctor at home or follow
him/her around town. I just mean that if you have an
appointment with your urologist or oncologist in June
or after that make sure you ask about the latest research from the AUA and ASCO. In addition, later
in the year one of the biggest radiation oncology
meetings in the world generally takes place and it is
called “ASTRO” (yes, like the dog from the Jetsons
cartoon), and you can ask your doctor about this
meeting. In addition, after these meetings are concluded, most medical libraries contain a copy of the
actual booklet from these meetings, which summarizes all of the latest research or the official web-sites
of these organizations will post several research articles. Therefore, I cannot stress enough in taking
some time to ask or research yourself the latest studies from these meetings.
Anyhow, have a safe and healthy start to your summer and I look forward to the next issue where we
will talk about more stuff. Also, I do not want to
leave this issue without congratulating the University
of Michigan Basketball team and the coach (Tommy
A.) for winning the NIT basketball tournament this
year - once again demonstrating that the University
of Michigan is the most powerful academic and athletic program in the universe (and I never ever exaggerate). By the way, my next prediction is that in
2005 the University of Michigan will win the NCAA
tournament in Basketball, Football, Hockey, Chess,
and prostate cancer debate…
26) DO COX-2 INHIBITOR ARTHRITIS
DRUGS SUCH AS CELEBREXВ®, VIOXXВ®, OR
BEXTRAВ® HAVE ANY RECENT RESEARCH
IN PROSTATE CANCER?
The answer is yes and no. Yes, there is some preliminary exciting small studies that have suggested
that men taking celebrexВ® for example for 1-year
(200 mg twice a day) after experiencing a rise in their
PSA after surgery or radiation treatment may have
actually experienced a slowing of their cancer growth
on these drugs as determined by their PSA change.
The problem with this and other studies is that they
are very small (in this case 12 patients and the article
was published in the British Journal of Urology) so it
is interesting but there are too few patients to draw
any serious conclusions about adding one of these
drugs to your program after experiencing a rising
PSA. Some guys are already on these drugs for pain
or for arthritis, and others are thinking about taking it.
Regardless, work this thing out with your doctor or at
least ask him/her about the latest data because we
will see more very soon.
Instead, they took simple steps proven to prevent infection
– they kept Adams warm during surgery, clipped his leg
hair instead of shaving it, and administered antibiotics at
the right time.
MEDIA RELEASE
Simple Steps Prevent Hospital Infections
The Grand Rapids Press
April 2004
By Rebecca Cook
Not all hospitals practice them, and a surgical infection
doubles a patient’s chance of dying.
BELLEVUE, Wash. – To prevent Scott Adams’ knee surgery from getting infected, doctors at Overlake Hospital
Medical Center didn’t need fancy new medicine or expensive equipment.
It’s easy, cheap and effective, but many hospitals fail to
take these steps.
Although fewer than 3 percent of the 30 million U.S. surgeries each year result in infection, the cost of treating it
raises the cost of hospital care and insurance. And getting
a surgical infection doubles a patient’s chance of dying.
A national survey of 39,000 operations in 2002 found
nearly half the patients did not get antibiotics at the correct
time, which is one of the best ways to prevent infection.
Health-care leaders are trying to reduce infection risk. By
concentrating on simple preventive measures, 56 hospitals
that took part in a government-sponsored project last year
succeeded in cutting their overall surgical infection rate by
27 percent.
The results were even more dramatic at Overlake Hospi-
tal, a 337-bed community hospital in suburban Seattle.
Overlake recently took part in a 13-month surgical infection prevention program run by Qualis Health, a Seattlebased health care quality improvement organization. The
hospital cut its number of surgical infections by more than
half, from 12 in 2002 to five in 2003. The hospital performs more than 14,000 operations annually.
Adams, a jovial 31-year-old engineer who blew out his
knee playing flag football, noticed the emphasis on preventing infection.
“Pretty much anybody who put a needle in me talked
about the risk of infection,” he said.
His leg hair was clipped instead of shaved because shaving causes tiny skin abrasions that can let in infection. He
got antibiotics exactly 20 minutes before his surgeon made
the first cut, the optimum time for getting the most infection-fighting power from the drugs. And doctors and
nurses kept him warm, which helped his body fight infection.
Adams particularly enjoyed the “bear hugger,” a comfortable puffy blanket filled with warm air, that he wore during surgery.
“I’ve got to get one of those for me at home,” Adams said.
He was recovering comfortably and infection-free a few
days after his anterior cruciate ligament (ACL) reconstruction surgery.
“I’ll be back playing football again next year,” he predicted.
About 780,000 surgeries lead to infections in the United
States each year, about 2.6 percent of the total.
A 1992 analysis published in the medical journal “Hospital Infections” found a surgical infection adds an average
of $3,152 to the patient’s hospital bill.
Other studies estimate that 40 percent to 60 percent of
surgical infections are preventable. The most powerful
preventive medicine is antibiotics, given within an hour of
incision. Give the drugs too early or too late, and they
will wear off or won’t get into the bloodstream fast
enough to work.
This isn’t new information. Studies dating to 1957 have
told doctors about the need for well-timed antibiotics.
So what’s the holdup?
“There are problems translating good research into actual
practice,” said Dr. Dale Bratzler, principle clinical coordi-
nator for the Oklahoma Foundation on Medical Quality
and a leader of the national Surgical Infection Prevention
Project. He is working with the authors of major antibiotic studies to set consistent national guidelines.
With 10,000 studies published every year, “there is no
physician that can keep up with all the publications,”
Bratzler said. “We need to make it more systematic.”
He said the best thing patients can do to protect themselves is to ask their surgeons about antibiotic treatment
and make sure to explain any drug allergies. Also, general
good nutrition and health will help, he said.
The healthier a patient is going into surgery, the smaller
the chance of infection.
LAC-PAACT 1UPDATE
By Gregory H. Teufel, Esq., Chairman2
We have been in contact lately with an inmate in a
Montana prison facing the unique challenge of seeking reasonable medical care for his prostate cancer
over the resistance of an uncooperative warden and
prison medical staff. We are providing him with
some informal thoughts and guidance and will keep
you updated on the status and hopefully the successful outcome of his struggle to obtain reasonable
healthcare.
We have also become aware of a patient of Dr.
Bahn’s in California who was recently denied coverage by Blue Shield for cryosurgery performed in November 2003. This is the first cryo denial we have
heard of in quite a while. We wish him the best and
will keep you updated on the status of that case as
well.
We have recently received a draft copy of a House
Concurrent Resolution sponsored by Rep. Nathan
Deal (R-GA), which states as follows: “Expressing
the sense of Congress with respect to the need to pro1
LAC-PAACT is PAACT’s legal advisory committee. Despite
the name of the committee, for various reasons, we generally
cannot give you legal advice or act as your personal attorney.
Please do not consider anything in this article as legal advice. If
you want legal advice, I encourage you to consult a lawyer in
your state, so that your specific situation and local laws can be
considered.
2
Gregory H. Teufel, Esq. is a partner in the Litigation Department of Schnader Harrison Segal & Lewis LLP's Pittsburgh
office. The views expressed are those of Mr. Teufel personally
and not of the firm.
vide prostate cancer patients with meaningful access
to information on treatment options, and for other
purposes. Whereas in 2004, it is estimated that approximately 230,000 new cases of prostate cancer
will be diagnosed in the United States, and nearly
30,000 men in the United States will die from prostate cancer; Whereas prostate cancer is the second
leading cause of cancer death in men in the United
States; Whereas over $4,700,000,000 is spent annually in the United States in direct treatment costs for
prostate cancer; Whereas African American men are
diagnosed with and die from prostate cancer more
frequently than men of other ethnic backgrounds;
Whereas increased education among health care providers and patients regarding the need for prostate
cancer screening tests has resulted in the diagnosis of
approximately 86 percent of prostate cancer patients
before the cancerous cells have spread appreciably
beyond the prostate gland, thereby enhancing the
odds of successful treatment; Whereas the potential
complication rates for significant side effects vary
among the most common forms of treatment for prostate cancer; Whereas prostate cancer often strikes
elderly people in the United States, highlighting the
importance of balancing the potential benefits and
risks of various treatments on an individual basis; and
Whereas Congress as a whole, and Members of Congress as individuals, are in unique positions to support the fight against prostate cancer, to help raise
public awareness about the need to make screening
tests available to all people at risk for prostate cancer,
and to provide prostate cancer patients with adequate
information to assess the relative benefits and risks of
treatment options: Now, therefore, be it Resolved by
the House of Representatives (the Senate concurring),
That it is the sense of the Congress that (1) national
and community organizations and health care providers have played a commendable role in supplying information concerning the importance of screening for
prostate cancer and the treatment options for patients
with prostate cancer; and (2) the Federal Government
and the States have a moral responsibility to ensure
that health care providers supply prostate cancer patients with appropriate information and any other
tools necessary for prostate cancer patients to receive
readily understandable descriptions of the advantages, disadvantages, benefits, and risks of all medically efficacious treatments for prostate cancer, including brachytherapy, hormonal treatments, external
beam radiation, chemotherapy, surgery, and watchful
waiting.”
We have written to Rep. Deal applauding his efforts
to ensure patients are aware and understand the
treatment options available to them for prostate cancer and, further to that purpose, we have asked that
he consider including cryosurgical ablation of the
prostate among the listed efficacious treatment options. We will let you know whether the final version
of this resolution, which is non-binding and has no
actual legal force, is amended to include mention of
cryosurgical ablation of the prostate as well. Failure
to mention that procedure would possibly hinder efforts of those who chose that treatment option and
who have been denied coverage, while mentioning it
might help them.
We want to keep you aware that the LAC-PAACT is
here to help you. We are particularly helpful in addressing insurance and Medicare coverage issues related to advanced cancer treatments. Please do not
hesitate to contact us regarding any coverage or other
legal issues related to advanced cancer treatments.
We are creating another supplement to the LACPAACT kit. Expect the new supplement to be available soon. Sorry that we are long overdue on updating the kit. If you have been denied coverage for an
advanced cancer treatment, be sure to let us know
and we will see if there is anything we can do to help.
Contact LAC-PAACT
If you have any questions or comments, or any suggestions about how LAC-PAACT can best serve your
needs, please do not hesitate to contact me. The preferred method to contact me is via email at
gteufel@schnader.com. You can also call me at
work at (412) 577-5289, home (412) 421-7123, or on
my cell phone (412) 596-6316, or send me a letter at
Schnader Harrison Segal & Lewis LLP, Suite 2700,
Fifth Avenue Place, 120 Fifth Ave., Pittsburgh, PA
15222 or a fax at (412) 765-3858. Please note that
requests for the LAC-PAACT kit should be addressed to PAACT. Contact information for PAACT
is on page 2 of this Newsletter. Please remember that
this article is not legal advice and I cannot generally
give you legal advice or become your personal attorney.
Board Certification
What Does It Mean?
By Stephen Barrett, M.D.
December 5, 2000
Question
I live in a Florida city that has a high percentage of
retired people and as a consequence, a large medical
services population. In their advertising it seems almost all the MD's are "Board Certified," but the
board is never mentioned. Somewhere, I heard that
there are a few boards considered to be "legitimate"
that require a high level of experience and recommendation, and who have passed stringent exams in
their specialty. Somewhere I learned there are boards
whose main purpose is to allow the use of "Board
Certified" after the name. Could you comment on
this? Is there a way to tell the difference?
Answer
Because the scope of modern medical knowledge is
vast, most medical school graduates take additional
training before entering clinical practice. Those
choosing to become specialists take at least three
years of residency training during which they are designated as PGY 1 (postgraduate-year-one resident),
PGY 2 (postgraduate-year-two resident), and so on.
The recognized standard-setting organization is the
American Board of Medical Specialties (ABMS),
which is composed of 24 primary medical specialty
boards and six associate members: the American
Hospital Association, American Medical Association,
Association of American Medical Colleges, Council
of Medical Specialty Societies, Federation of State
Medical Boards of the United States, and National
Board of Medical Examiners. The American Osteopathic Association (AOA) sets standards for osteopathic physicians (DOs) who undergo residency
training at osteopathic institutions. (ABMS also certifies DOs who train at MD-run programs.)
Medical specialty boards require high standards of
training and performance and ensure them by rigid
examinations. Successful applicants receive diplomas
and are considered "board-certified." They are also
referred to as "diplomates" in their particular specialties. The number of ABMS-approved credentials has
risen sharply during the past ten years. Certificates
are now available for 37 specialties and about 75 subspecialties [1]. Most certificates expire within seven
or ten years and require reexamination for renewal.
Physicians who complete all requirements for certification except the examination may be identified as
"board-eligible." Although the American Board of
Medical Specialties has officially abandoned the
term, it is still in common use.
In 1995, Medical Economics magazine reported that
more than 75 boards not ABMS- or AOA-affiliated
had issued certificates to thousands of physicians.
Although a few of these self-designated boards are
run legitimately and may eventually achieve ABMS
or AOA recognition, most do not require residency
training in their specialty. The author stated that
"some physicians use fringe board certification to attract patients, who usually don't know the difference.
. . . And only a handful of states restrict the advertising of board certifications or specialties." [2] Certification by any of the following suggests that a practitioner is involved with dubious methods:
•
•
•
•
American Board of Chelation Therapy
American Board of Holistic Medicine
American Board of Environmental Medicine
International Board of Environmental Medicine
Most physicians identified as specialists in the Yellow Pages have completed accredited specialty training. However, telephone directory publishers rarely
attempt to verify credentials, so self-proclaimed specialists may be listed also. The ABMS Verification
Service provides a simple way to check whether a
doctor has ABMS-recognized certification. The
Board also has been placing lists of board-certified
physicians in many telephone directories, but many
board-certified physicians are not included because
they do not wish to pay the required fee (over $200
per year).
Reference
1. ABMS Web site, July 1998. The list spans seven
pages. To navigate, use the "Next Page Down" link at
the bottom of each page.
2. Terry T. Visit Vegas! Get your boards while you're
there. Medical Economics 72(3):26-36, 1995.

AHA! - March/April 2015 - Manchester Artists Association

Welcome Contact Us

To see how Sapiens did all that, you can read our

to read more - Remembering Lee Kuan Yew

4v4 Variations

Data supplement 1

A Rational Approach to Design of Tee Shear Connections

- Paladin Longview

Silver Serpents – Light filaments within the Plasma

First Aid - The District of Oak Bay

plastic dog - PDF eBooks Free | Page 1

ESECA Master of Science and Technology

WyHigh Update Bulletin Issue 11

- Refugee Council

JLA Mindfulness course 2015 MEDICARE REBATES

to view the early sale bill.

Mayfield High School Night with the Cavaliers!

Tap for Burn-Out Flier - Sweet Home Sweet Ride

Workforce Planning – Nurses and Midwives

Future Stars Camp - Mayville State University Athletics

Humane Lobby Day 2015 Agenda/FAQ

ECOS 34-1-66 Book Reviews - British Association of Nature