nsights PCRI A Repor t f rom the E xecut ive D...

PCRI
Patient & Physician in Co-Partnership
nsights
New Developments in Prostate Cancer Treatment
MAY 2005 VOL 8: NO 2
The PCRI Today: A Repor t f rom the Execut ive D irector
As PCRI approaches its tenth anniversary, it is useful to look back briefly at
the early days of the organization in
contrast with the PCRI today. PCRI
was founded by two prostate cancer
oncologists, Drs. Stephen Strum and
Mark Scholz. Drs. Strum and Scholz
were hopeful that an organization
combining insightful clinical research
with high-level educational activities,
PCRI Executive Director,
directed to both the patient and the
Glenn D. Weaver
physician, would greatly enhance outcomes for prostate cancer patients everywhere.
Over the years, the PCRI has changed from a founder-driven
clinical research-based organization to a mission-based organization, and as such the mission of the PCRI has evolved into the
vital role of disseminating information and prostate cancer education and patient awareness:
The Prostate Cancer Research Institute’s mission is to
improve the quality of men’s lives by supporting research
and disseminating information that educates and empowers patients, families and the medical community.
The evolution of the PCRI has reflected the changes that have
taken place in the prostate cancer community as a whole. There
are a number of leading
organizations that are The goal of education is the
committed to the fight advancement of knowledge
against prostate cancer. and the dissemination of truth.
Among them are
–John F. Kennedy
(alphabetically listed)
the American Cancer Society, the American Society of Clinical
Oncology, the American Urological Association, the Foundation
for Cancer Research & Education, Patient Advocates for Advanced
Cancer Treatment, the Prostate Cancer Foundation, and Us TOO
International – as well as the PCRI.
continued on page 11
A B O U T T H E M E D I C A L A RT I C L E S I N T H I S I S S U E
What Every Doctor Who Treats Male
Newer Concepts in the Treatment of
HRPC with Bone Metastases
Patients Should Know
By Oliver Sartor,MD
By Stephen B.Strum,MD,FACP and Donna Pogliano
Bone metastases with pain represent a
common and significant problem for
patients with advanced prostate cancer.
Data from prospective randomized clinical trails now support the use of Samarium-153-EDTMP in patients with Hormone-Refractory PC and painful bone
metastases. Pain relief and decreases in
analgesic consumption can be expected in
the majority of patients treated. Side
effects are limited to transient and relatively mild platelet and white blood cell
suppression. Combination therapies that
incorporate cytotoxic agents such as Taxotere in combination with Strontium-89
or Samarium-153-EDTMP regimens are
now being actively explored in clinical trials. This approach has the potential of
promoting synergy between active agents.
Preliminary data suggest that this might
be of considerable interest.
This article is directed at General Practitioners and other medical professionals
who are not familiar with modern prostate
cancer clinical practice. The article covers
screening tools such as PSA and uPM3,
describes how to differentiate benign
prostate conditions from prostate cancer,
and explains the role of such PSA derivatives as free-PSA percentage, PSA velocity,
and PSA doubling time.The article goes on
to discuss slow-growing versus aggressive
prostate cancer as diagnosed by PSA level,
PSA doubling time, Gleason score and other biomarkers, and how this information
affects the decision between active objectified observation and immediate local therapy. Dr. Strum concludes that with this
information we can detect prostate cancer
at a time when currently available therapies
are most likely to cure the disease.
Who’s Really at Risk for What?
By Mark C.Scholz,MD and Ralph Blum
Dr. Scholz is struck by the prodigious
efforts men make to understand and get
appropriate treatment for prostate cancer
while ignoring the fact that they are at
greater risk of dying from other causes
unrelated to prostate cancer. Therefore, he
has written this article to provide advice
to prostate cancer patients about health
issues unrelated to prostate cancer. The
goal of the article is to bring the risks
associated with prostate cancer into perspective with the risks of other potentially serious illness, including heart attacks,
osteoporosis, colon cancer, sarcopenia,
lung cancer, and melanoma. For each of
these diseases, he suggests preventive
and/or early detection steps men can and
should take. The article is accompanied
by a useful description of laboratory
blood tests and what they may reveal.
Newer Concepts in the Treatment of
Hormone-Refractory Prostate Cancer with Bone Metastases:
Combinations of Bone-Seeking Radiopharmaceuticals and Chemotherapy
Oliver Sartor, MD Chief, Hematology-Oncology Section; Director, Stanley S. Scott Cancer Center, LSU Health Sciences Center, New Orleans, LA
PAIN FROM BONE METASTASIS IS ONE OF THE
MOST DIFFICULT CLINICAL PROBLEMS IN
PATIENTS WITH HORMONE-REFRACTORY
PROSTATE CANCER (HRPC). Radiographic
evidence of distant metastatic spread to bone
occurs in the vast majority of cases of latestage disease, and in most patients these
lesions are osteoblastic (bone-forming) in
nature.
The most reliable method of detecting
bone metastases in a prostate cancer patient
is a conventional bone scan.However,even in
a patient with prostate cancer, not all areas of
enhanced uptake on bone scan are associated
with metastatic disease, particularly in the
case of solitary lesions or uptake in joints.
Confirmation of metastases by additional
imaging modalities such as plain radiographs
or MRI scans may be needed prior to making
a clear diagnosis. Bone metastases may or
may not be associated with painful symptoms when initially detected.1
In patients initially diagnosed with bone
metastases and then subsequently treated
with hormonal therapy, Newling and colleagues have determined that increases in
serum PSA occur approximately six months
99m
Tc-MDP
Anterior
153
prior to changes in bone scan which in turn
occur approximately four months prior to
patient reports of pain.2 The timing of this
sequence of events in patients treated with
hormonal therapy before the onset of bone
metastases (most patients today) has not
been well studied, but the interval between
PSA rise and the onset of a positive bone scan
is suspected to be much longer (more than
two years on average).
Even in patients with a positive bone scan
who report painful symptoms, a comprehensive examination may be needed to establish
the cause of the pain and evaluate any possible complicating factors such as spinal cord
compression, neuropathic conditions, and
pathologic fractures. Patients with bone
metastases may also have non-malignant
sources of bone pain, and the causes of such
pain need to be evaluated on a case by case
basis.It is not uncommon for arthritis or other benign problems to cause pain in a patient
with cancer.
A number of therapies for advanced
prostate cancer are available, including secondary hormonal manipulations, external
beam radiation, bone-seeking radiopharma-
Sm-EDTMP
99m
Tc-MDP
Posterior
Conventional bone scan (99mTc-MDP) versus 153Sm-EDTMP demonstrating identical uptake.
153
Sm-EDTMP emits an imageable 103 keV gamma photon that can be viewed up to 3-5 days after the
initial injection by either planar or single photon emission computed tomography (SPECT). Uptake and
distribution of 153Sm-EDTMP are similar to those of 99mTc-MDP used in bone scans. Comparison of the
two images produced by gamma radiation emitted by gamma radiation emitted from 153Sm-EDTMP
and 99mTc-MDP in the same patient illustrates how similar the radiographs produced by 153Sm-EDTMP
are. Thus, 153Sm-EDTMP may also be used for diagnostic imaging. Images courtesy of Todd Hoover.
2
PCRI INSIGHTS
ceuticals, and systemic chemotherapy (see
Table 1). External beam radiation provides
excellent palliation for focal painful lesions,
but in patients with systemic disease, repeated courses are typically required for effective
treatment.
The approach to decreasing the intensity
of pain from bone metastases varies depending on a number of factors including degree of
symptoms, extent of disease and prior treatments. Analgesics, anti-tumor agents, hormones, chemotherapy, steroids, local surgery,
bisphosphonates, anesthesia, and radiation
therapy (local and systemic) are all appropriate treatments under selected circumstances.
In general, a combination of systemic and
local modalities is required, and no single
treatment regimen is effective for an extended
period of time. Of the many options available
for HRPC, one treatment option that I will
focus upon in this brief discussion involves
the newer concept of combining intravenous
radiopharmaceuticals with chemotherapy for
possible synergy.
Three radionuclides are currently
approved for the treatment of metastatic bone
pain: phosphorous-32 (32P), strontium-89
(89Sr or Metastron), and samarium-153
(153Sm-EDTMP or Quadamet). These
radionuclides all localize to regions of
enhanced bone turnover and deliver high
local doses of radiation through the emission
of beta particles.The mechanism of bone targeting varies for each of them. Phosphorous32 is targeted to bone through inorganic
phosphate pathways while strontium-89 is
taken up as a calcium analog. Samarium-153
is targeted to bone via its chemical conjugation to EDTMP (ethylenediaminetetramethylenephosphonic acid). The relevant
nuclear decay properties of these radionuclides are shown in Table 2.
Decay properties such as half-life and particle energy play significant roles in such
important clinical characteristics of these
agents as onset and duration of palliative
effects and degree of and time to recovery
from bone marrow suppression. The particle
emission energies of 32P and 89Sr and the corresponding ranges in bone and soft tissue are
NEWER CONCEPTS IN THE TREATMENT OF HRPC
FROM PAGE 2
radionuclides in combination with chemomuch greater than those of 153Sm.Higher enerTable 1. Therapies for
therapeutics.The first of these trials was pubgy particles are associated with greater marHormone-Refractory Prostate Cancer
lished by Tu and colleagues5,who used a comrow toxicity as the result of the larger volumes
bination of 89Sr and doxorubicin.Patients were
of marrow exposed to radiation. The shorter
1. Anti-androgen (bicalutamide,
153
randomized to receive either doxorubicin
physical half-life of Sm (1.9 days) results in a
nilutamide, flutamide) withdrawal
alone or in combination therapy after first
more rapid delivery of radiation than either 32P
2. Anti-androgen (bicaluitamide,
being treated with a combination therapy of
(14.3 days) or 89Sr (50.5 days). For example,
flutamide, nilutamide)
ketoconazole, doxorubicin, estramustine, and
delivery of 90% of the total dose of radiation
administration
vinblastine. Of note, this combination of
requires approximately 3.5 half-lives of decay,
3. Adrenal suppressives such as
agents is no longer used. Only patients with
a time interval of approximately one week for
ketoconazole
153
32
89
stable disease or responding disease after the
Sm,seven weeks for P and 25 weeks for Sr.
4. Estrogens such as DES plus warfarin
preliminary therapy were eligible for the ranThe current relative indications and con5. Glucocorticoids such as prednisone
domization. Patients randomized to the comtraindications for the use of bone-targeted
or dexamethasone
bination of 89Sr and doxorubicin had a longer
radiopharmaceuticals are presented in Table
6. Bisphosphonates (zolendronate in
survival compared to those patients who were
3. Baseline complete blood counts are necesbone scan positive patients)
treated with doxorubicin alone.This trial supsary to establish adequate pretreatment levels
7.
External
beam
radiation
therapy
ports the concept that targeting bone and
of platelets and white blood cells since all of
using a radiosensitizing chemotherapy (in
8.
Bone-seeking
radiopharmaceuticals
these agents result in some suppression of
combination) might be an effective therapeu(bone
scan
positive
patients)
bone marrow function. Severe renal dysfunctic approach.
9. Chemotherapy (docetaxel,
tion is a contraindication to the use of bonemitoxantrone, etc.)
Preliminary data is available regarding the
targeted radionuclides because currently
combination
of 153Sm-EDTMP and docetaxel
available agents are predominantly excreted
10. Experimental Therapies
in patients with hormone refractory prostate
by the kidney.
cancer. In a phase I study conducted in
Several prospective randomized
Table 2. Nuclear Decay Properties and
3,4
Sweden by Widmark and colleagues6
controlled studies have been perBone Penetration Depth of Radionuclides
that examined preliminary efficacy, six
formed to evaluate the effectiveness of
Approved for Treatment of Metastatic Bone Pain
patients were treated with weekly docusing bone-seeking radiopharmaceutiHalf-life β-Emission Penetration
Radionuclide
etaxel at a dose of 30 mg/m2, in combicals to relieve the pain of bone metas(days)
(Avg, MeV)
(mm)
nation with a dose of 1.0 mCi/kg given in
tases in HRPC patients. One of the
Phosphorous-32 14.3
0.7
2.7
week four, 24 hours prior to treatment
largest of these trials was published by
Strontium-89
50.5
0.58
2.4
4
with docetaxel.38 Optimal uptake by
Sartor and colleagues in 2004 evaluatSamarium-153
1.9
0.22
0.55
tumor sites was seen 8-24 hours after
ing 153Sm-EDTMP. In this prospective,
injection.
Five of the six patients had a
multi-center, randomized, double-blind,
decrease
in
PSA of >50% and four of the six
placebo-controlled study in patients with
Table 3. Indications and
had
a
decrease
in PSA of >80% which persistbone metastases from hormone-refractory
Contraindications to the use of Bone
ed
for
more
than
six months.Toxicity was not
prostate cancer,152 patients were randomized
Targeted Radiophamaceuticals for
dose
limiting;
only
one episode of neuin a 1:2 ratio to placebo (n=51) or a 1.0
Treatment of Metastatic Bone Pain
tropenic fever was reported.This study clearly
mCi/kg dose of the active drug (n=101) and
deserves additional follow up and expanded
Indications
were followed for up to 16 weeks.Pain intensipatient numbers.
ty was measured twice daily (by patients)
❍ Bone Scan Positive
In another preliminary study (by Arnsusing validated linear and non-linear scales.
• Osteoblastic Lesions
meier and colleagues)7, six patients with
Daily opioid analgesic use was also recorded.
❍ Bone Pain Due to Cancer
metastatic prostate cancer were treated with
Patients who received the active drug exhibit❍ Multi-focal Disease
paclitaxel 200 mg/m2 q for three weeks with
ed significant improvements (as compared to
Relative Contraindications
estramustine and of 153Sm-EDTMP. Subsethe placebo group) in pain scores at each of
quent groups of six patients were each treated
❍ Predominant Soft-tissue Pain
the first four weeks following administration.
with paclitaxel 90 mg/m2 q for three weeks.
This decrease in pain occurred while pain
❍ Unifocal Bone Lesions
153
Sm-EDTMP was administered with chemomedications were decreased.These data clear❍ “Osteolytic”Lesions
153
therapy, starting with a dose of 1 mCi/kg and
ly demonstrate that Sm-EDTMP can reduce
• Poor Uptake on Bone Scan
escalating in 0.5 mCi/kg dose increments.
pain from bone metastases in patients with
Absolute
Contraindications
Moderate decreases in white cells were seen in
HRPC. Toxicity was mild and was limited to
❍
Severe
Marrow
Suppression
one of the six patients at the 1.5 mCi/kg dosetransient decreases in white cells and platelets.
level, but no significant toxicity had been
❍ Severe Renal Dysfunction
Recently, considerable interest has
emerged in the use of skeletal targeted
continued on page 10
PCRI INSIGHTS
3
What Every Doctor Who Treats Male Patients Should Know
Stephen B. Strum, MD, FACP Medical Oncologist Specializing in Prostate Cancer and Donna Pogliano Prostate Cancer Advocate
Clinical Practice Prostate
Cancer Diagnosis Guidelines
Starting at forty years of age, every man
should have an annual PSA (prostate-specific
antigen) test and a DRE (digital rectal examination).Men at risk due to a family history of
prostate cancer (brothers,fathers)1-3,men with
a family history of breast cancer (mothers,
sisters, aunts)1,4-6 and African-American men
should begin annual screening at age 35. A
PSA of 2.0 and over at any age should be
investigated to rule out prostate cancer.
A first step in investigation of a PSA
elevated at 2.0 or above should be a
free-PSA percentage test.
• A free-PSA percentage of more than 25%
is associated with a low risk of prostate
cancer.
• A free-PSA percentage of less than 15%
is associated with a higher risk of
prostate cancer7.
An elevated PSA and a correspondingly
low free PSA percentage can be caused by
prostatitis, which is a benign rather than a
malignant condition.If prostatitis symptoms
are noted and/or if expressed prostatic secretions are consistent with prostatitis, four to
six weeks of Cipro or similar antibiotic
should be prescribed prior to recommending
a biopsy. At the end of the Cipro therapy, a
repeat PSA determination should be made.If
there is significant lowering of the PSA, an
element of prostatitis is likely to be present.
The PSA value after antibiotic therapy will
more aptly reflect the status of the patient in
the situation where a diagnosis of prostate
cancer is subsequently established.
BPH (benign prostate hyperplasia) does
not cause a low free PSA percentage. It may
cause an elevated PSA, however. Therefore, in
the case of an elevated PSA but a high free
PSA percentage (equal to or greater than
25%),an estimate of gland volume by DRE or
via transrectal ultrasound of the prostate may
reveal findings consistent with a diagnosis of
BPH.A general rule of thumb is that an accurate gland volume (best determined by transrectal ultrasound of the prostate) x 0.066 will
equal the amount of benign-related PSA.
Therefore, assuming only the presence of
4
PCRI INSIGHTS
BPH, a 60-gram or 60 cubic centimeter
prostate is entitled to secrete approximately
3.96 ng of PSA into the blood.
PSA velocity (PSAV) and PSA doubling
time (PSADT) are important markers that
can indicate the existence of prostate cancer.
Blood sampling for PSA determinations,done
at least three months apart, and by the same
laboratory using the same testing procedure,
are necessary to establish PSAV and PSADT.
The validity of such determinations is
increased if such testing involves at least three
determinations over an 18-month span of
time. However, a progressive and serial
increase in PSA values should raise concern
that prostate cancer is present and that a
greater degree of vigilance is mandatory.
• A PSAV that exceeds 0.75 ng/ml/yr is
associated with a higher probability of
PC.8
• A PSADT of less than 12 years is associated with a higher probability of PC.
PSA readings that bounce up and down
are more indicative of a benign process
than a malignant process. A PSA that shows
a persistent rise over time, particularly three
consecutive rises three months apart,is suspicious for prostate cancer regardless of the PSA
level. Any amount of PSA in excess of the
measured benign-related PSA should be considered to have been produced by a malignant
process until proven otherwise.
Recently,an additional new screening tool
has become available. Bostwick Laboratories
now offers the uPM3 test, the first urinebased genetic test for prostate cancer.uPM3 is
based on PCA3, a specific gene that is profusely expressed in prostate cancer tissue. On
average, the amount of PCA3 is 34 times
greater in malignant prostate tissue than it is
in benign prostate tissue.No other human tissues have ever been shown to produce PCA3.
The uPM3 test predicts cancer as confirmed
by prostate biopsy with 81% accuracy, compared to 47% accuracy for PSA. Therefore,
after an elevated PSA, further investigations
might reasonably include uPM3 testing to
enhance the accuracy of diagnosis. Systematic biopsy of the prostate under ultrasound
guidance, however, remains the definitive
diagnostic procedure when clinical and/or
laboratory findings indicate the possibility of
prostate cancer.
An approach using biological detection
techniques such as those described above
would eliminate advanced presentations of
PC. Annual screening in this manner presents
us with an opportunity to detect localized PC
in over 95% of men.9 Such statistics offer an
outstanding chance for a curative approach to
this disease.
An approach involving these profiling
techniques allows the patient-physician team
to discern the three major types of PC manifestation using the analogy of the tortoise,the
hare and the raven (see Figure 1).
The tortoise represents the very slow
growing presentation of prostate cancer that
may be monitored using active objectified
surveillance (so-called watchful waiting) as
opposed to the garden variety prostate cancer
case (the hare),for which local treatment typically results in long-term biological eradication of disease.Most importantly, attention to
PSA kinetics accomplished by monitoring the
PSA and PSA derivatives such as free-PSA
percentage, PSADT, PSAV and other calculations, should result in an almost total disappearance of the highly aggressive presentation of prostate cancer (the raven). This latter
presentation is most commonly associated
with rapidly progressive disease and fatality.
However, the more typical presentations of
prostate cancer (the hare) would be diagnosed years earlier if attention was directed to
PSA kinetics, along with confirmatory tests
such as free PSA, uPM3 and other new diagnostic advances. Such earlier diagnosis of
prostate cancer, and for that matter any type
of cancer,is associated with a lesser volume of
cancer, a decrease in the risk of spread of the
disease and thus a greater likelihood of cure
with local therapy.
These opposite extremes in the clinicopathological nature of prostate cancer, i.e.,
the very slow growing variants versus the
aggressive ones, are important to differentiate due to the highly different evaluation and
management recommendations advised for
each circumstance.
CONTINUED FROM PAGE 4
Slow-Growing versus
Aggressive Prostate Cancer
Slow-growing variants in general, have low
PSA values (under 10) and long doubling
times (greater than 24 months and often 48
months or longer), as well as low PSA velocities (<0.75 ng/ml/yr ± 10%). If a biopsy is
done on a patient with a PSA that is under 10,
the Gleason score often turns out to be (3,3).
Depending on the calculated tumor volume,
clinical stage, PSA doubling time, and other
factors, these objectified biologic parameters
may allow many such patients to be candidates for active objectified surveillance (also
called watchful waiting).10 Patients who
choose to monitor their illness rather than
seek immediate local therapy must be cognizant of the significance of change in biology
over time, or biologic trend. They need to be
aware that if manifestations of disease progression become evident, their situation
should be reevaluated.In such circumstances,
consideration must be made for some form of
local treatment – before the window of opportunity for successful local therapy is lost.
Aggressive variants, in general, have high
PSAs (over 10) OR very low PSAs associated
with very aggressive, high Gleason score
[(4,3), (4,4), (4,5), (5,4), (5,5)] cancers. These
variants are very dangerous, often escaping
investigation for long periods of time because
the PSAs appear to be in the so-called normal
range. Investigating all PSAs of 2.0 and over
will help to catch these aggressive prostate
cancers while they are still organ-confined
and treatable with local therapies such as
surgery and radiation. The probability of
detecting these low PSA/high Gleasonscore cancers is enhanced if patients and
doctors monitor even very low PSA levels
over time to note any persistent increases.
High Gleason score cancers often have
reverted to an embryonic state in which PSA
secretion into the blood is markedly reduced.
Checking the serum for abnormal elevations
in markers such as CGA (Chromogranin A),
NSE (Neuron Specific Enolase), CEA (Carcino-Embryonic Antigen) and PAP (Prostatic
Acid Phosphatase) is important to discern PC
activity secondary to these de-differentiated
tumor cell populations. Therefore, in cases
Figure 1.PC Biology Made Simple.Prostate cancer can be thought of as being indolent,intermediate or aggressive.The indolent subtype (the tortoise) is slow moving and slow growing and rarely leaves the prostate gland.It can
be rationally managed by active objectified surveillance.10 The intermediate subtype (the hare), without proper
attention and treatment can escape the confines of the prostate and result in morbidity and mortality.The aggressive,sinister and often lethal subtype (the raven) is fortunately uncommon and is associated with high mortality but
perhaps with more aggressive monitoring and preventive strategy we can minimize this biologic presentation.
such as this, the normal guidelines for PSA
velocity and doubling time may not be applicable. HOWEVER, the concept of slope or
trend in a biomarker of disease activity
remains valid, and any biomarker elevation
should be tracked at regular intervals to determine the presence of abnormal growth of
primitive (embryonic) tumor cell clones.
connection when it comes to men with PC?11
Aren’t the 300,000 American lives lost each
decade too great a price to pay?
Working together and listening attentively
to the biology of cancer, we will achieve vast
inroads into the diagnosis, evaluation and
treatment of this illness and alter the course of
human lives. ■
Conclusion
References
If we scientifically observe the biological manifestations of prostate health or disease, we
can detect PC at a time when currently available therapies are most likely to cure the most
common malignancy facing man. If we
ignore the biological communications that
can alert us to the presence of a life-threatening condition, we will miss a vital opportunity to change the course of the illness.
The loss of life, productivity, and the
extreme costs to the health care system—all
of which result from a late-stage diagnosis of
this disease—should provide impetus for all
of us to be proactive when it comes to an early diagnosis of a malignant condition. This
fundamental concept has been heralded for
many malignances, such as cancer of the
cervix,lung cancer,colorectal malignancy and
breast cancer. When will we make the same
1. Cerhan JR, Parker AS, Putnam SD, et al: Family history and prostate
cancer risk in a population-based cohort of Iowa men. Cancer Epidemiol Biomarkers Prev 8:53-60, 1999.
2.Hayes RB,Liff JM,Pottern LM,et al: Prostate cancer risk in U.S.blacks
and whites with a family history of cancer. Int J Cancer 60:361-4,
1995.
3. Isaacs SD, Kiemeney LA, Baffoe-Bonnie A, et al: Risk of cancer in relatives of prostate cancer probands.J Natl Cancer Inst 87:991-6,1995.
4.Bennett KE,Howell A,Evans DG,et al:A follow-up study of breast and
other cancers in families of an unselected series of breast cancer
patients. Br J Cancer 86:718-22, 2002.
5. Ford D, Easton DF, Bishop DT, et al: Risks of cancer in BRCA1-mutation carriers. Breast Cancer Linkage Consortium. Lancet 343:692-5,
1994.
6. Goldgar DE, Easton DF, Cannon-Albright LA, et al: Systematic population-based assessment of cancer risk in first-degree relatives of
cancer probands. J Natl Cancer Inst 86:1600-8, 1994.
7.Ito K,Yamamoto T,Ohi M,et al: Free/total PSA ratio is a powerful predictor of future prostate cancer morbidity in men with initial PSA
levels of 4.1 to 10.0 ng/mL. Urology 61:760-4, 2003.
8. Ito K,Yamamoto T, Ohi M, et al: Usefulness of prostate-specific antigen velocity in screening for prostate cancer. Int J Urol 9:316-21,
2002.
9. Labrie F, Candas B, Cusan L, et al: Diagnosis of advanced or noncurable prostate cancer can be practically eliminated by prostate-specific antigen. Urology 47:212-7, 1996.
10.Hardie C,Parker C,Norman A,et al: Early outcomes of active surveillance for localized prostate cancer. BJU Int 95:956-60, 2005.
11. Labrie F, Candas B, Dupont A, et al: Screening decreases prostate
cancer death: first analysis of the 1988 Quebec prospective randomized controlled trial. Prostate 38:83-91,1999.
PCRI INSIGHTS
5
Who’s Really at Risk for What?
By Mark C. Scholz, MD Director, Prostate Oncology Specialists, Marina del Rey, CA, and Ralph Blum PC Survivor
Editor’s Note: This is an article by Dr. Scholz
providing advice to prostate cancer patients
about health issues unrelated to prostate cancer.
The goal of the article is to bring the risks associated with prostate cancer into perspective with
the risks of other potentially serious illness,
including heart attacks, osteoporosis, colon cancer sarcopenia, lung cancer, and melanoma.
Cancer is the Spur
Like many doctors, I am often struck by the
prodigious efforts men make to understand
and get appropriate treatment for prostate
cancer (PC) while ignoring the fact that they
are at greater risk of dying from other causes
unrelated to PC.
I’ll never forget the unexpected phone call
I received from the distraught wife of a 55year-old patient who had consulted me for the
first time only a week previously. “How did
you know?”she cried.“How did you know that
my husband had heart disease?”At first I didn’t even understand what she was referring to.
Then she told me that her husband had died
in his sleep from a massive heart attack four
days after our initial consultation. During our
initial consultation, I had only recommended
that he undergo screening to see if any heart
disease was present. There had been no indication whatsoever that he had an underlying
heart problem during the initial evaluation.
One thing I did know, however, is that silent
heart disease is very common among men in
this age group.
Deeply sorry for her loss, I explained to
her that men come to my office because of
their concern about dying of PC. When I see
them, they are often found to have low-risk
variants of PC,a form of the disease that pracTable 1. Annual U.S. Male Death Rates
Heart Disease
Lung Cancer
Stroke
Accidents
Emphysema
Diabetes
Prostate Cancer
Flu/Pneumonia
Colon Cancer
Suicide
6
PCRI INSIGHTS
350,000
89,000
65,000
63,000
62,000
31,000
28,000
27,000
25,000
23,000
tically never leads to death. I point out to
them that that they are 10 times more likely to
die of a heart attack or a stroke than from
their early stage PC.See Table 1 for the annual
death rates for men in the United States each
year.
For this reason, I routinely recommend
cardiac screening to our newly diagnosed PC
patients, even though they usually try to tell
me what good shape they are in, how low
their cholesterol is, and generally how good
they feel.
For the past decade,my focus has been on
treating PC exclusively.Some forms of PC can
be quite dangerous. Fortunately, these more
aggressive forms are not as common as the
lower-grade, less dangerous forms. These
days, when men are commonly being diagnosed at an early stage,we can confidently tell
them that their risk of dying of PC within 10
years is less than 1%. However, their risk of
dying from other diseases can be far greater,
so I customarily advise my patients that they
at least undergo screening for certain common, preventable, and potentially dangerous
diseases.
The place to start is with a simple baseline
physical examination that includes some common blood tests looking for any irregularities
that might indicate the presence of underlying
illness. (The accompanying article on page 10
describes these laboratory blood tests, discusses what they test for,and projects what the
results may indicate.) Screening for unexpected latent medical problems is not always a
popular pursuit. It can be inconvenient,
uncomfortable, and on occasion, expensive,
since sometimes insurance does not pay for
screening tests. Also troubling is the fact that
the screening process can occasionally produce a false positive or a false negative. So it
might take additional studies to validate a
finding, causing additional stress and cost for
the patient. Despite all these drawbacks,
screening is our best defense, and is the best
tool available for early detection of certain
common and preventable heath problems.
The Scanning Revolution
Fortunately, times are changing and rapid
progress is occurring in the field of medical
technology. One of the most significant
advances has been the refinement of a body
scanning technique called computerized
tomography, popularly referred to as CT
scans.Body scans have been around for some
years now, but older technology could not
accurately image moving organs.If we use the
analogy of a camera,the older scans could not
take pictures of the moving parts of the body
because they had “excessively slow exposure
times.” “Pictures” of moving organs like the
heart, the lungs, and the colon always came
out blurred.Today,however,newer technology
renders excellent image quality.
I am not advocating that total body scans
should be undertaken randomly or without
explicit reason such as those procedures that
are being widely advertised on the radio in
major population centers. The value of this
sort of global scanning is highly debatable
because random scanning frequently uncovers what we term “incidental findings” that
subsequent tests show to be completely
benign. The disadvantage of global body
scanning is that when any slight abnormality
is seen, it becomes necessary to embark on a
stressful, time-consuming, and expensive
process to determine that a suspicious area
found in the scan does or does not indicate
the beginning of some malignant process.
This then can require further scans, blood
tests,consultations with medical experts and,
in some cases,biopsies or even surgery.
However, there are selective ways that
these scans can be used to image certain critical areas of the body, especially in groups of
patients known to be at high risk. One of the
areas where fast CT scans are beneficial is in
detecting the presence of cholesterol plaque in
the coronary arteries. Patients in our practice
(who are usually older than 50) belong to the
population most at risk for atherosclerosis,
otherwise known as hardening of the arteries.
Simply described,hardening of the arteries
occurs when cholesterol builds up in the arteries.In extreme degrees the buildup reaches the
point where the artery is totally blocked off.
When an artery to the heart is completely
blocked, it results in a heart attack. When an
artery to the brain is completely blocked off, it
results in a stroke. Over 400,000 men die of
either heart attack or stroke every year. Perhaps twice that many men have non-fatal
strokes and heart attacks each and every year.
Clearly, we have an epidemic on our hands. In
WHO’S REALLY AT RISK FOR WHAT?
comparison, the annual death rate from PC is
28,000, only 9% of the rate that men are dying
from heart attacks and strokes.
Much of the mortality from heart disease
is preventable. The problem is that atherosclerosis is a silent disease until suddenly a disaster occurs. There are indirect means (e.g.
cholesterol testing) to estimate the likelihood
of impending serious atherosclerosis,yet these
tests are too imprecise. Elevated blood cholesterol provides a warning by telling how much
cholesterol is floating in the blood,but we want
more. We really want to know how much
cholesterol is sticking to the wall of the artery.
This varies widely from individual to individual even in men with really high or low levels
of cholesterol floating in the blood.
Fast CT scanning can accurately evaluate
the status of the coronary arteries. Population
studies indicate that a lucky minority of men
have absolutely no calcified plaque at all. The
rest of us have small amounts, average
amounts, or extensive amounts of disease. In
the United States, having an “average”amount
of plaque is a serious situation. With heart
attacks and strokes at epidemic levels,is seems
foolish to be unwilling to have a simple 10
minute $300 test to determine the status of
one’s arteries. This does not require annual
testing; reevaluations can probably be done
every three to five years.
FROM PAGE 6
porosis. Osteoporosis is defined as bone that
has been weakened from calcium loss over
time. Calcium loss is a silent phenomenon
until a bone fracture occurs.Common fracture
sites from osteoporosis are the spine,rib,wrist,
and hip.Osteoporotic fractures often have dire
consequences. Bone fractures are associated
with shortened survival in men with PC.1
Compression fractures of the spine can be
extremely painful, result in loss of height and,
when advanced, result in a forward curvature
of the spine known as the “dowager’s hump.”
Osteoporosis is mistakenly thought to
occur only in women,but fully a third of all hip
fractures occur in men. There are many causes of osteoporosis. Men who are slender have
less bone reserve and are more predisposed to
osteoporosis.Thyroid or parathyroid hyperactivity can contribute to osteoporosis. Other
contributing causes of osteoporosis are excessive use of alcohol, caffeine, or tobacco. Cortisone, used to treat asthma or arthritis, is
another common culprit. Excess vitamin A
has also been associated with osteoporosis
and fractures.2 Lack of exercise, lack of sunlight exposure (low vitamin D),and low calcium intake are additional potential causes.
Osteoporosis-induced bone fractures are
even more frequent in men treated for PC with
testosterone inactivating pharmaceuticals
(TIP).3,4 Testosterone deprivation therapy
reduces estrogen levels. Normal levels of both
these hormones inhibit excess calcium loss
from bone.
Osteoporosis needs to be identified by
scanning before a fracture occurs, but not all
scans are equally effective. It is important to
choose the right scanning technique to diagnosis osteoporosis because the most popular
equipment available, DEXA scans, grossly
underestimate the incidence of osteoporosis
in men.5 The problem with DEXA scans is that
men over age fifty usually have some degenercontinued on page 9
EBCT “positive” for coronary calcium
Check List for Plaque Management
What should you as a PC patient do if you
learn that there is a lot of cholesterol plaque in
your coronary arteries?
1. See a qualified cardiologist;
2. Obtain a cardiac stress treadmill
annually;
3. Obtain an ultrasound of your carotid
arteries;
4. Start Lipitor to diminish your LDL
cholesterol to 60;
5. Start aspirin 81 mg a day (if there are no
contraindications to aspirin);
6. Check homocysteine.If it is elevated,start
taking folic acid 1 mg daily;
7. Reduce blood pressure to 125 over 75 or
less;
8. Diet and exercise;
9. Perform a repeat scan in three years to
make sure what you are doing is working.
Atherosclerosis
(Above) Figure 1.
Progressive development of plaque over
time. This process, in
various stages of development, can be seen in
many areas of the
coronary artery system,
consistent with the “diffuse” nature of coronary artery disease.
(Left) Figure 2.
The calcium impregnation of the plaque as
would be visualized by
the scanner.
The Specter of Osteoporosis
We must also consider the problem of osteoPCRI INSIGHTS 7
WHO’S REALLY AT RISK FOR WHAT?
FROM PAGE 7
ative arthritis of the lower back which results in excess calcium in the tissues surrounding the spine.When the DEXA scan sends x-rays through this
area to measure spine density, the excess calcium surrounding the spine
results in an artificially high bone density reading, a situation that masks
the presence of osteoporosis in the spine.
Fortunately,another more accurate technique of measuring bone mineral density is available: the quantitative CAT scan,or QCT.This scan measures
the calcium density in the center of the vertebral column thereby bypassing
the problem of the excess calcium surrounding the spine. Many health care
providers are unaware of the DEXA scan’s limitations,although these limitations have been well documented in a study from Massachusetts General Hospital.6 The study compared DEXA and QCT in 41 men with PC who had never previously been treated with TIP.QCT detected osteoporosis in 63% of the
men but DEXA only found osteoporosis in 5%! On the basis of this study,
which was done in men whose average age was 68, we can conclude that
osteoporosis is common even in men who have never had previous exposure
to testosterone-lowering drugs.
What do you do if you find out that you have
osteoporosis?
In these QCT scans, the yellow lines demark the area of bone being analyzed.
Courtesy of Parkview Imaging.
1. Start calcium citrate 500 mg twice a day;
2. Start prescription Vitamin D (Calcitriol);
LABORATORY TESTS DEFINED
An important first step in the screening procedure is,
of course, the physical examination taken at the first
visit of a patient to our practice and scheduled to be
repeated each year thereafter.In addition to the tactile
examination,a complete physical will include a number of blood tests which, when analyzed, can provide
an early indication of disease or incipient disease.
The results of the laboratory results are written in a
shorthand code that your physician can readily
interpret, but that might just bewilder you as a
patient.For each blood test result,the report includes
(1) an entry in a column for your quantitative results
and (2) an entry in a column presenting the reference range for males. In addition, if one of your
results is outside of this range,that result is flagged so
you can quickly see anomalous results.
But what are these tests? What do they measure? What
is the possible significance of an anomalous result?
The following will answer these questions for you.
BMP: BASIC METABOLIC PANEL
The GLU test measures blood glucose levels that
vary before and after meals. Patients with diabetes
have blood sugar levels that remain persistently elevated. Low levels of glucose occur in patients on
macrobiotic diets and are desirable in prostate cancer patients because less sugar is available to the
growing tumor cells.Low levels of glucose in diabetic patients can be indicative of excess medication or
insulin. Since blood glucose varies, a better way to
diagnose diabetes is the glycohemoglobin blood
test.An abnormal GLU result may cause your doctor
to prescribe this additional blood test.
Elevation of Blood Urea Nitrogen (BUN) can
result from dehydration or from a high protein diet
but it can also be a result of a kidney malfunction (but
when this is the case there is almost always simultaneous elevation of the creatinine level as well).BUN is
very sensitive, and a modest elevation of BUN does
not necessarily indicate a need for intervention. Low
BUN levels have no implications of consequence.
Creatinine (CREAT) is a fairly accurate indication of
kidney efficiency. Elevated levels of creatinine are
indicative of kidney impairment.The development of
creatinine elevation above previous baseline signals
the need for further tests. Minor elevation of creatinine can be seen from aging and is usually not significant if the minor elevation remains stable.Low creatinine levels have no implications of consequence.
The concentration of Sodium (Na) in the blood is
regulated by the kidneys and adrenal glands.Drinking
too much water can cause abnormally low amounts in
the blood, but so does heart failure or kidney malfunction. Hence, levels of sodium outside the normal
range represent a significant problem that needs evaluation and correction.
Small amounts of Potassium (K) can be measured
in the blood.Blood levels outside the normal range are
of critical significance.Low blood levels of potassium
result from diuretics (water pills) when there is an
inadequate amount of potassium replacement. High
blood levels can result from kidney disease or from
excess potassium replacement. Occasionally, potassium can be elevated in the breakdown process of the
red blood cells (hemolysis), which occurs when the
blood is being drawn.When hemolysis is suspected,
the blood draw is repeated to determine if the potas-
sium elevation is artifactual.Levels of potassium outside the normal range represent a significant problem
that needs evaluation and correction.
Abnormal Chloride (CL) levels usually accompany abnormalities of sodium or potassium.
Borderline low or high levels of chloride generally have no significance.
Calcium (Ca) blood levels are tightly regulated by
parathyroid hormone and vitamin D. Over-active
parathyroid glands can also cause excess blood levels
of calcium.Grossly elevated calcium levels are dangerous and can cause sleepiness and heart arrhythmias.
Low levels of calcium can cause muscle spasms,typically in the hands. Low levels of calcium can also be
observed in patients with low albumin levels (protein
levels) in the blood. Elevated levels of calcium can
occur by taking excess amounts of vitamin D. The
accuracy of the blood calcium can be confirmed with
a more accurate test called ionized calcium.
HEPATIC PANEL (Liver function tests)
Transaminases (AST/ALT) are the most sensitive
indicators of liver cell irritation or damage. AST and
ALT (also known as SGOT and SGPT) can occasionally elevate to minor degrees from viral infections or
from excess alcohol. Larger degrees of elevation can
occur as a result of toxicity from medications or from
cancer spread.AST/ALT elevation can also occur after
a heart attack.Low levels of AST/ALT are of no significance.
Blood bilirubin (TBIL) levels are reflective of the
rate that the body recycles the red cells in the blood;
bilirubin is a breakdown product of old, used up red
cells. Elevations of bilirubin can occur with bile duct
blockage if the red cell breakdown process is acceler-
3. Start a bisphosphonate such a Fosamax,
Actonel,Aredia or Zometa;
4. Exercise (preferably some form of weight
lifting);
5. Repeat bone density testing every year to
ensure that the treatment is working;
6. While on treatment,consider checking
the urine for signs of excess bone breakdown products with tests such as
Pyrilinks D and N Telopeptide to make
sure that the treatment is working.
Colon Cancer
This cancer kills about the same number of
men in the United States each year as PC does.
Early diagnosis with colon screening can
detect the disease long before it spreads.Generally,it is recommended that colon screening
occur every five years with either a colonoscopy (a scope performed by a physician
called a gastroenterologist), or with a fast CT
scan,which is termed a virtual colonoscopy.
ated by disease.A mild chronic elevation of bilirubin
may be a benign genetic condition that does not cause
illness. (DBIL) is a sub fraction of bilirubin. Relative
changes of the two forms can help distinguish the different causes of bilirubin elevation.
Alkaline Phosphatase (ALP) is another indicator
of liver health and function.ALP is also a produced in
the bones so elevations of ALP can occur either from
problems originating from the liver or bone or both.
Liver cell function problems can cause an elevation of
ALP in a manner similar to AST/ALT.ALP is also sensitive to blockage of the bile ducts,so elevations ofALP
in conjunction with elevations of Bilirubin indicate
bile duct blockage.Low ALP levels are not of concern.
Total Protein (TP) is a simple measure of the
amount of protein in the blood including albumin.
The non-albumin portion of the blood includes antibodies,that function as a portion of the immune system. Elevated levels of TP can be seen in immune
derangements where antibodies are over-produced.
Albumin is the most common protein circulating in
the blood. Albumin fulfills a number of functions
such as maintaining vascular blood volume, binding
hormones,and acting as a storage reserve for protein.
Low albumin levels are reflective of malnutrition,liver
disease,or kidney disease.Elevation of albumin levels
is usually minor and of no consequence.
CBC: COMPLETE BLOOD COUNT
The CBC contains several different measures of
importance though for PC patients the real issue is the
presence or absence of anemia.Anemia is the relative
reduction of red cells in the blood resulting in a
decrease in oxygen carrying capacity. Severe anemia
can be felt as tiredness and shortness of breath.Ane-
Advantages of Virtual
Colonoscopy
Disadvantages of Virtual
Colonoscopy
✔ Minimal if any risk of colon perforation
✔ No need for sedation
✘ May not be quite as accurate
✘ Regular colonoscopy will be required
Advantages of Colonoscopy
✔ Effectiveness is more established
✔ If any polyps are visualized,they can be
removed during the procedure
Beware of Sarcopenia
Sarcopenia is the official word describing loss
of muscle mass. Muscle loss is a normal part
of aging. Some men age gracefully, but others
don’t. Men who allow themselves to get weak
are the ones who look and act old. Strength is
what we associate with heath and youthfulness. Weakness is associated with advanced
age and decrepitude. Muscle loss can have a
dramatic effect on health.Studies indicate that
poor fitness in the elderly is more dangerous
than smoking.Table 2 shows the predicted 10year survival of normal healthy individuals at
mia is measured by three factors in the CBC: Hematocrit (HCT),Hemoglobin (HGB), and Red Blood
Count (RBC).An HCT level less than 40 in men constitutes a low level.Symptoms of tiredness and shortness of breath do not usually occur until the HCT
declines to around 32 though there are occasional
exceptions. A low HCT is treatable with a non-toxic
substance called Erythropoietin.
The other important measures in the CBC take on
more significance in patients receiving chemotherapy.
Chemotherapy can cause reductions in Platelet
count (PLT) and White blood count (WBC).
Platelets help the blood clot normally. White blood
cells are part of the immune system.The WBC is broken down into Granulocytes (GRAN) and Lymphocytes (LYM).An elevated level of granulocytes is
indicative of an underlying bacterial infection. Viral
infections can cause low lymphocyte counts. MCV,
MCH, and MCHC are measures of red cell dimensions.MCV is the most commonly utilized.Low MCV
can be seen in iron deficiency and in a congenital anemia called thallassemia.High MCV can be seen in liver disease and B12 deficiency. RDW is a measure of
red cell size variability. Elevation of RDW can occur
early in the development of iron deficiency.
LIPID PANEL
Triglyceride (TRIG) is simply another name for fat.
Elevated fasting triglyceride levels indicate a higher
risk for coronary arteriosclerosis. However, transient
declines in the White Blood Count (WBC) and the
triglyceride levels are not as accurate predictors of
arteriosclerosis as cholesterol.
Previously, total cholesterol (CHOL) levels of
over 200 were thought to be indicative of an
increased risk for arteriosclerosis. This is true
if anything is detected
Disadvantages of Colonoscopy
✘ Sedation is often required
✘ A small risk of colon perforation
an average age of 65. In this study, subjects
were divided into three groups: the strong,the
average,and the weak.Despite having no specific illnesses at the time,only 60% of the weak
individuals were still alive ten years later.
continued on page 10
Table 2. Fitness Predicts Survival
Degree of Fitness
Superior
Average
Inferior
Ten-year survival
90%
75%
60%
but better indicators have been developed.
Low Density Lipoprotein (LDL) cholesterol or
“bad cholesterol”is an indicator for the risk of developing arteriosclerosis. The American Heart Association recommends that LDL cholesterol should be less
than 100 to prevent deposition of cholesterol on the
arterial wall.Modern statin drugs such as Lipitor dramatically lower LDL levels in the blood and can lead to
reversal of blood vessel clogging.
High Density Lipoprotein (HDL) cholesterol
is called “good cholesterol” because higher levels
of HDL protect against the development of arteriosclerosis by scavenging excess cholesterol
from the walls of the blood vessels. The HDL level can be increased with exercise and niacin.
Studies show that the higher the level of HDL the
lower the risk for heart disease. Levels of HDL
that are under 40 represent a particular concern.
OTHER TESTS
Ultra-sensitive Thyroid Stimulating Hormone
(TSH) is the hormone that stimulates thyroid hormone production. Elevated levels of TSH indicate
blood levels of thyroid hormone are inadequate. Low
levels of TSH indicate that the thyroid may be overactive. If patients are already taking thyroid hormone,
TSH can be used to ensure that the correct amount of
hormone is being administered.
C-Reactive Protein (CRP) is a protein marker
for inflammation. Elevated levels are usually
caused by infections and arthritic conditions.More
recent studies have shown that abnormal levels are
also associated with an increased risk of heart
attacks and colon cancer, soPCRI
CRP
results are9 now
INSIGHTS
given equal weight to CHOL results.
WHO’S REALLY AT RISK FOR WHAT?
Ninety percent of the people in the strong
group were still alive 10 years later. Loss of
strength is correctable to a large degree with
appropriate exercise.
Exercise is unpleasant for most of us. My
approach has been to purchase discipline and
expertise by hiring a trainer. I spend one hour
twice a week taking orders from a ruthless
individual who has a mandate to make me
stronger. This process is accomplished exclusively with weight machines.Aerobic exercise is
great, but optimally it should be done for 40
minutes a day.I just don’t have that kind of time
to spare.I have been doing this one-hour,twiceweekly regimen for five years. It has been
expensive and mostly unpleasant, but the
results are rather remarkable. I used to have to
eat selectively to avoid gaining weight. Now I
eat pretty much whatever I want without any
concern for my weight. I am about twice as
strong as I was five years ago. I have put on at
least 15-20 pounds of muscle and lost 20-30
pounds of fat.In my professional life I can work
longer hours at a faster pace, but at the end of
the day I still have energy to interact with my
family. For our patients, this issue of muscle
loss is even more critical.Men with PC who are
being treated with testosterone-inactivating
pharmaceuticals loose muscle mass very, very
quickly.The muscle loss is preventable but only
with a consistent weight training program performed for an hour twice a week.7
Lung Cancer
Early diagnosis of lung cancer is vital,since it is
almost universally fatal in men who are not
diagnosed until after they have a symptom of
the disease such as cough,chest pain,or weight
loss. The average survival is only nine months
in men diagnosed after they have symptoms.
Fortunately,fast CT scans can detect small early stage lung cancers when they are only a quarter of an inch in diameter.When a lung cancer
is found at such an early stage, it can often be
removed with a telescopic device in a process
called thoracoscopy. (This is very similar to
laparoscopy for operations in the abdominal
area.) Cure rates for men with small lung cancers are high (about 80%).Any life-long smoker would be crazy not to spring for $300 each
year to have a lung scan done.
Less Common Cancers
Bladder cancer
Bladder cancer kills about six thousand men
each year, five times less than PC. The pres10
PCRI INSIGHTS
FROM PAGE 9
ence of bladder cancer is often signaled by
microscopic amounts of blood in the urine
which can be detected by performing a simple urine analysis. So obviously a urine analysis should be done as part of the general
annual physical examination.
Melanoma
Three thousand men die each year from
melanoma,a pigmented cancer that can look
like a new mole in its early stages.There is no
effective treatment for melanoma after it has
spread, but if it is detected early, it is usually
curable with surgical excision. An annual
visit to the dermatologist (the doctor with
the trained eye for spotting melanoma in its
earliest stages) can save your life.
Other Causes
I can’t resist making a common sense statement in an area where I have no specific
expertise. Consider that just as many men are
dying in car accidents each year as are dying
each year from PC. If that is the case, what are
some simple precautions? Consider keeping a
robust grid of steel around you while you are
doing battle on the highways; stay away from
sub-compact cars. Drive a heavy car that has
front and side air bags. And of course wear a
seat belt. Harkening back to my Internal
Medicine training leads me to also mention
that the next most common killer after PC is
pneumonia and flu. While most men have
heard of flu vaccines, many are unaware that
there are now FDA approved antibiotics to
treat flu: Tamiflu, and Flumadine. These are
very effective against influenza if they are
started promptly after the onset of symptoms.
They can also be helpful in the situation where
one family member is sick; in that case, the
drugs can be taken before the flu develops and
thereby may preclude the development of illness. I have also found that many men are
unaware that there is now an effective vaccine
against pneumonia available called pneumovax.The pneumovax is administered every
five years and is recommended for men over
age 65 or for men with chronic illnesses.
Conclusion
Many of these illnesses can be prevented by an
annual visit to the doctor’s office.But it takes a
lot to get us guys to go to the doctor. Prostate
cancer seems to do the trick.A diagnosis of PC
shatters the illusion of immortality.Men finally sit up and take notice that good health is not
a guaranteed right.Therefore,the diagnosis of
PC may actually turn out to be beneficial if
being diagnosed can lead to an increased
awareness of health-related issues that have
been previously neglected. Common sense
dictates that if it is worth expending considerable time, energy, and resources to minimize
the chance of death from PC, it certainly
makes sense to expend time and energy to
minimize the risks of these other preventable
causes of death.■
References
1. Skeletal fractures negatively correlate with overall survival in men
with prostate cancer.Oefelein,M,Ricchiuti,V,et al Journal of Urology
Vol.168: 1005-1007,2002.
2. Excess dietary intake of vitamin A is associated with reduced bone
mineral density and increased risk of hip fracture. Ann Intern Med
Vol.129: 770-778,1998.
3. Osteoporosis after orchiectomy for prostate cancer.Daniell,H,Journal
of Urology Vol.157,439-444 ,1997.
4. Osteoporosis in men treated with androgen deprivation therapy for
prostate cancer. Ross, R, Small, E, Journal of Urology Vol. 167: 19521956,2002.
5. Low bone mineral density in hormone-naïve men with prostate cancer.Smith,M,McGovern,F,et al Cancer Vol.91: 2238-2245,2001.
6. Exercise capacity and mortality among men referred for exercise testing. Myers, J. New England Journal of Medicine Vol. 346 page 793
2002.
7. Resistance exercise in men receiving androgen deprivation therapy
for prostate cancer.Segal RJ: J Clin Oncol 21:1653-9,2003.
NEWER CONCEPTS IN THE
TREATMENT OF HRPC FROM PAGE 3
reached at the time of the report.
Chemotherapy, particularly with nonbone marrow suppressing agents such as
weekly taxanes, 5-FU infusion, or
capecitabine, clearly has the potential to
augment activity of bone-seeking radiopharmaceuticals and additional studies
are warranted to determine best dosing,
best agents, and optimal timing of such
therapies.
Summary and Conclusion
Bone metastases with pain represent a
common and significant problem for
patients with advanced prostate cancer.
Data from prospective randomized clinical
trails now support the use of 153Sm-EDTMP
in patients with HRPC and painful bone
metastases. Pain relief and decreases in
analgesic consumption can be expected in
the majority of patients treated. Side effects
are limited to transient and relatively mild
platelet and white blood cell suppression.
Combination therapies that incorporate
continued at right
THE PCRI TODAY: FROM THE EXECUTIVE DIRECTOR
There are three basic functions that the
prostate cancer community performs:
1. Research
2. Support
3. Patient Education & Awareness
In the past, there has been functional
overlap in the services that these and other organizations provide. But I believe that
today the lines of demarcation are becoming much sharper. Ultimately, it would be
in the best interest of the PC community if
the primary functions of the PC organizations were more in line with their missions. In this way, the pooled efforts would
be greater as a whole, rather than fragmented among individual organizations
spending resources on activities, however
useful, that are outside the scope of their
primary mission.
The PCRI, in pursuing its primary goal
of fostering public awareness of prostate
cancer and educating prostate cancer
patients, their families, and their family
doctors to the disease, its prevention, and
its treatment options, has expanded its
programs to take advantage of additional
media. In the past year, for example, we
have augmented our unique Insights
newsletter/journal and our national
NEWER CONCEPTS IN THE
TREATMENT OF HRPC FROM PAGE 10
cytotoxic agents in combination with 89Sr
or 153Sm-EDTMP regimens are now being
actively explored in clinical trials. This
approach has the potential of promoting
synergy between active agents.Preliminary
data suggest that this might be of considerable interest, although additional trials are
needed to optimize this approach. ■
FROM PAGE 1
Helpline programs with educational programs that have appeared on PBS and cable
TV; we have produced a DVD explaining
prostate cancer issues and the PCRI’s role
in dealing with them; and we have produced educational mailers on these subjects for groups such as Blue Cross/Blue
Shield of Florida members, general practitioners, and the general public.
All of these expanded activities are
important to our mission, but they do cost
money. Therefore, the PCRI is embarking
upon an educational campaign to find a
national sponsor willing to support the
fight against prostate cancer with funds
and mass media exposure.We feel that this
support, plus a continuation of generous
contributions from people like you, our
subscribers, will enable us to pursue the
ambitious program that is so important to
the fulfillment of our mission.
And we hope that you will continue to
rely on the PCRI for the most accurate,
timely, and useful information about
prostate cancer. We further hope that you
will join with us in our campaign to reach
other men at risk from prostate cancer by
directing them to the PCRI cost-free information conduits: (800) 641-PCRI,
www.pcri.org, and of course, Insights.
How to
Contribute
Please help PCRI continue its mission of providing information and
education about prostate cancer
through its programs, such as this
newsletter, in the following ways:
• Direct Donation: Cash, check,
or credit card; stock or real estate
• Memorial and Honorarium
Contributions: Honoring
someone you care about with a
memorial or commemorative gift
• Payroll Deduction: Federal
employees can contribute to the
Combined Federal Campaign in
their workplace.To find PCRI’s
CFC number, look in the HEALTH
section of the CFC directory or
call PCRI.
• Planned Giving: Naming PCRI
in your will or as beneficiary of a
life insurance policy.
Your tax-deductible gift in the form
of cash, stocks or real estate
should be made payable to ”PCRI”
and mailed to PCRI at:
5777 W. Century Blvd., Suite 800
Los Angeles, CA 90045
Federal Tax ID Number: 95-4617875
PCRI Helpline
800-641-7274
[email protected]
www.pcri.org
Credit card donations can be
made online at: www.pcri.org or
by calling (310) 743-2116.
For further information, contact
PCRI at [email protected].
Prostate Cancer Research Institute is a non-profit
corporation, exempt from federal income taxes
under section 501(c)(3) of the Internal Revenue
Code. It has been classified as an organization that
is not a private foundation as defined in section
509(a) of the Code, and qualifies for a maximum
charitable contribution by individual donors.
References
1. Gandhok N and Sartor O. Bone-targeted therapy for prostate cancer. In: Klein EA, ed. Current clinical urology: Management of
prostate cancer, second edition. Totowa: Humana Press,
2004:589-606.
2. Newling DW, Denis L,Vermeylen K. Orchiectomy versus goserelin and flutamide in the treatment of newly diagnosed metastatic prostate cancer. Analysis of the criteria of evaluation used in
the European Organization for Research and Treatment of Cancer-Genitourinary Group Study 30853. Cancer 1993;72(12 suppl):3793-3798 .
3. Serafini AN, Houston SJ, Resche I, et al, Palliation of pain associated with metastatic bone cancer using samarium-153 lexidronam: A double-blind placebo-controlled study. J Clin Oncol
1998;16:1574-1581.
4. Sartor O, Reid RH, Hoskin PJ, et al, Samarium-153-lexidronam
complex for the treatment of painful bone metastases in hormone refractory prostate cancer. Urology 2004;63:940-945.
5. Tu SM, Millikan RE, Mengistu B, et al.Bone-targeted therapy for
advanced androgen-independent carcinoma of the prostate: a
randomised phase II trial. Lancet. 2001; 357(9253):336-41.
6. Widmark A, Linne T, Modig H, Johansson L. Optimizing the
time of co-administration of docetaxel and samarium-153 for
advanced androgen independent carcinoma of the prostate
[abstract]. Proc Am Soc Clin Oncol 2003;22:433.
7. Arnsmeier SL, Spies S, Shervin D, et al. Phase I/II study of taxane and estramustine with samarium in patients with hormone
refractory prostate cancer [abstract]. Proc Am Soc Clin Oncol
2004;23:438.
The Prostate Cancer Research
Institute’s mission is to improve
the quality of men’s lives by
supporting research and
disseminating information that
educates and empowers
patients, families and the
medical community.
PCRI INSIGHTS
11
The Ostrich
Seven years ago, poet Ric Masten was diagnosed as
having the deadly neuroendocrine prostate cancer,also
known as non-secreting-PSA prostate cancer. This
diagnosis came as a complete surprise. As he now
recalls,“Like most older men I had avoided the annual
checkup for years.The proverbial ostrich with his head
stuck deeply into the sand of the workaday world.I felt
fine so why bother? Of course,what really kept me out
of the doctor’s office was the thought that he just might
find something wrong.”
Over the years, he has developed a close relationship
with the PCRI’s Program Director, Harry Pinchot, and
he now is an active advocate for annual checkups
(www.ric-masten.net).
For the past six
years,
CONTINUED HEADER
FROM
PAGEhe
1 has
been sending poems and updates on his fight with cancer (www.ric-masten.org).He is no longer an ostrich.
THIS ISSUE
The PCRI Today
Newer Concepts in the Treatment
of HRPC with Bone Metastases
What Every Doctor Who Treats
Male Patients Should Know
Who’s Really at Risk for What?
The Ostrich
PCRI
Published By
nsights
Prostate Cancer Research Institute
5777 W. Century Blvd., Suite 800
Los Angeles, CA 90045
PROSTATE CANCER HELPLINE
800-641-PCRI or 310-743-2110
PCRI ONLINE
www.pcri.org
EMAIL
[email protected]
1
2
4
6
12
after the original diagnosis and treatment
I became the classic “ostrich”
head thrust deep in the sand of denial.
I did my best
to keep myself in the dark
and during
that blind unattended time
my disease sneaks up on me
morphing into the very aggressive
dedifferentiated neuroendocrine carcinoma
the label alone
being a head’s up eye opener!
at long last I faced the fact
that the ostrich cannot fly
time to take an active role
in my fight for survival
time to look the monster in the eye
so I go on line where dumb luck
and a benevolent “search engine”
find the Prostate Cancer Research Institute.
I dial the “helpline”
and for more than an hour
an anonymous Good Samaritan
calmly slowed me down until
my philosophy of life could catch up
and begin to see me through.
once again I’m able to recall
that only where the path of difficulty
crosses the easy way
can growth and change occur,
that the height of my highest high
is in direct proportion
to the depth of my “deepest down”
lessons I’d lost sight of
when my butt was in the sky
and my brains were under ground.
PCRI
nsights
Editor:
Review Board:
Design & Production:
Charles Bader
Duke K. Bahn, MD
Stanley A. Brosman, MD
Arthur N. Lurvey, MD
Mark C. Scholz, MD
Diana Garnand
Prostate Cancer Research Institute
5777 W. Century Boulevard, Suite 800
Los Angeles, CA 90045
Phone (310) 743-2116 | Fax (310) 743-2113
Helpline (310) 743-2110 E-mail: [email protected]
www.pcri.org and www.prostate-cancer.org
Executive Director: Glenn D. Weaver
E-mail: [email protected]
Board of Directors
Chester A. Swenson, President
Chairman,Marketing & Financial Services Enterprises
Jerome Seliger, PhD, Vice President
Professor of Health Administration,
California State University, Northridge
Barry L. Friedman, JD, Secretary
Attorney at Law
T. Kent Graham, Treasurer
Financial Consultant, T. Kent Graham & Associates
Duke K. Bahn, MD
Director, Prostate Institute of America
Stanley A. Brosman, MD
Pacific Urology Institute, Pacific Clinical Research
Brian L. Gauthier, MBA
Gauthier Management Company
Arthur N. Lurvey, MD
Medicare Contractor Medical Director
Jerry Peters
MCG Records
Claudia B. Sangster, Esq.
Director of Philanthropy Services, myCFO, Inc.
Mark C. Scholz, MD, PCRI Co-founder
Director, Prostate Oncology Specialists
The cost of printing and mailing this newsletter
is made possible through a generous grant from
The Life Extension Foundation
P.O. Box 229120, Hollywood, FL 33022
800-544-4440 www.lef.org/prostate
The opinions expressed in the by-lined articles are
those of the authors and should not be considered
opinions of the PCRI. © Copyright 2005.