Merry Christmas to you! Please check out these sites for prostate cancer info.
www.prostateoncology.com
http://pcribc.org/forum.php
We are excited about 2013 and we'll see you in the new year.
BLOGGERS: MARK SCHOLZ, MD & RALPH H. BLUM
The co-authors of Invasion of the Prostate Snatchers, blog alternate posts weekly. We invite you to post your comments.
Tuesday, December 25, 2012
Tuesday, December 18, 2012
Urologist and Radiation Therapist Attitudes toward Active Surveillance
BY MARK SCHOLZ, MD
In May of every year over 10,000 medical oncologists from around the world attend a 5-day meeting sponsored by the American Society of Clinical Oncology (ASCO) where preliminary results of the latest cancer research are presented. Thousands of research projects are summarized and published in short 300-word abstracts. What follows is a long quote of almost the entire abstract published in 2012 by Dr. Simon Kim from the Mayo Clinic:
In May of every year over 10,000 medical oncologists from around the world attend a 5-day meeting sponsored by the American Society of Clinical Oncology (ASCO) where preliminary results of the latest cancer research are presented. Thousands of research projects are summarized and published in short 300-word abstracts. What follows is a long quote of almost the entire abstract published in 2012 by Dr. Simon Kim from the Mayo Clinic:
“While active surveillance is well recognized as an
acceptable treatment strategy for low-risk prostate cancer, the extent to which
radiation oncologists and urologists perceive active surveillance as effective
and routinely recommend it to patients is unknown. Therefore, we sought to
assess the attitudes and treatment recommendations for low-risk prostate cancer
from a national survey of prostate cancer specialists.
Methods: A
mail survey was sent to a population-based sample of 1,439 physicians in the
U.S. from late 2011 and early 2012. Physicians were queried about their
attitudes regarding active surveillance and treatment recommendations for
patients diagnosed with low-risk prostate cancer (PSA<10 ng/dl; Stage = T1c;
Gleason 6 in one of twelve cores).
Results: Overall,
321 radiation oncologists and 322 urologists completed the survey for a 45%
response rate. Most physicians reported that active surveillance is effective
for low-risk prostate cancer (71%) and stated that they were comfortable routinely
recommending active surveillance (67%). Urologists were more likely to agree
that active surveillance is effective (77% vs. 67%; p=0.005) and were
comfortable recommending active surveillance (74% vs. 61%; p=0.001) compared
with radiation oncologists. Most physicians recommended radical prostatectomy
(47%) or radiation therapy (32%), but fewer endorsed active surveillance (21%)
for low-risk disease. After adjusting for physician covariates, radiation
oncologists were more than eleven-times more
likely to recommend radiation therapy, while urologists were 4.7-times more
likely to recommend surgery and 2.1 times more likely to recommend active
surveillance for low-risk prostate cancer.
Conclusions: Although
active surveillance is widely viewed as effective by radiation oncologists and
urologists, most urologists continue to recommend surgery, while most radiation
oncologists recommend radiation therapy. Our results may explain in part the
relatively low contemporary use of active surveillance in the U.S.”
My Comment:
This study clearly documents that urologists and radiation therapists, while
acknowledging that active surveillance is acceptable, overwhelmingly recommend
surgery and radiation. Not surprisingly, the urologists recommend surgery and
the radiation therapists recommend radiation. The study findings are remarkable
because they were not generated by a third party. This report depicts urologist
and radiation therapist behavior though a self-description
survey. Clearly, broader acceptance of active surveillance will be impeded
until the day when urologists and radiation therapist physicians are willing to
act on what they know to be true about active surveillance rather than simply
giving it lip service.
Labels:
active surveillance,
ASCO,
prostate cancer,
urologists
Tuesday, December 11, 2012
The FDA and Its Firing Squad (Combidex Part 3)
BY RALPH BLUM
Although the transcripts of FDA meetings are a matter of record, they are not that easy to find. What’s more, they are not indexed so you have to dig. When I finally read the minutes and watched a video of the March 3, 2005 ODAC meeting, it was painfully obvious that there was plenty of blame to go around. But the way Combidex—NDA Application 21-115—went down really pissed me off.
After interviewing several staff members at Ad Mag, I became very aware of the financial reality. Contrast agents are not economically viable. Subjected to all the same requirements as a drug, a contrast agent like Combidex can cost over $100 million to develop, and the likelihood of FDA approval is increased by having a narrow indication. But here’s the irony: the narrower the indication, the less chance the company will ever recoup its money.
There are a number of things concerning Invasion of the Prostate Snatchers of
which I am proud. Two in particular stand out.
First, that despite his full and demanding
schedule, Mark Scholz and I were able to collaborate effectively to produce
this book. I have received a whole
heap of emails from men thanking us and pointing out that, as far as they know,
it is the first time in the literature on prostate cancer where the voices of
doctor and patient were heard speaking as peers, each presenting those aspects
of the disease he considered of primary importance to the newly diagnosed.
Second, it was both surprising and gratifying
to learn that Snatchers had been
awarded the 2011 Nautilus Book Award Gold Medal for “Conscious Media and
Investigative Reporting” as the result of our tracking down the FDA rejection
of Combidex. Since many of you have not read our book, and I know of no other
readily available report on that destructive process, I want to review it here
as part of the Combidex story.
I was determined to find out
why the FDA had rejected Combidex back in 2005. I started by tracking down
Jerome Goldstein, the former CEO of Advanced Magnetics (Ad Mag), the Cambridge,
Massachusetts company that had marketed Combidex. I found him through his golf
club, the Country Club in Brookline.
“So what do you want to know?” Goldstein asked.
“What went wrong? Why did the FDA reject Combidex? And can I
quote you?”
“I’m retired now,” Goldstein said in a gruff voice. “so I
suppose you can quote me.
Some of the blame was ours. Our
application was too broad. We should have gone for disease specificity. But
that’s only part of it. The FDA bureaucrats in ODAC were also to blame.
ODAC—that’s the Oncologic Drugs Advisory Committee—has total control over the
life and death of every new drug application. And because of ODAC’s decision, prostate
cancer patients are dying and suffering needlessly.”
Ad Mag’s fatal error was that
instead of specifying Combidex as a contrast agent for establishing lymph node
involvement in one type of cancer—prostate
cancer—they had tried to broaden its application to cover all cancers. They
should have known better. Once it has FDA approval for a single “indication,” it
is legal for doctors to use a drug “off label,” meaning, wherever, in their
judgment, it is useful.
I asked Goldstein if it was
possible to obtain a transcript of the ODAC meeting, and he told me that their
meetings were a matter of public record. Then, in a low angry growl, he said,
“Nobody should ever die from this disease. It’s a crime.” I was about to hang
up, when he said, “You know I have prostate cancer. I was diagnosed two years
ago. Gleason 6. My internist said I should do surgery or put seeds in.”
“So what did you do?”
“Nothing.”
“Nothing?”
“Well, not exactly nothing. I bought a new putter.”
Although the transcripts of FDA meetings are a matter of record, they are not that easy to find. What’s more, they are not indexed so you have to dig. When I finally read the minutes and watched a video of the March 3, 2005 ODAC meeting, it was painfully obvious that there was plenty of blame to go around. But the way Combidex—NDA Application 21-115—went down really pissed me off.
ODAC found lots to attack. One
patient went into anaphylactic shock from the Combidex. They delivered CPR and
epinephrine, but it was too late: the man died at the hospital thirty-five
minutes later. The fact that this single death had occurred a decade earlier,
and had resulted in an immediate shift in method of delivery—from injection, to
dilution of the contrast agent in saline and use of slow infusion—did not
reassure the FDA. When I went through the Combidex records, I learned that the
man who had died was so eager to participate in the trials that he failed to
disclose his allergic condition, or that he had gone into anaphylactic shock on
other occasions. Ad Mag pointed out that the vast majority of test subjects had
only very minor and transient adverse (mainly allergic) reactions and that only
four out of 1,236 patients had experienced a more serious adverse reaction.
There had been no further deaths and no serious side effects.
After interviewing several staff members at Ad Mag, I became very aware of the financial reality. Contrast agents are not economically viable. Subjected to all the same requirements as a drug, a contrast agent like Combidex can cost over $100 million to develop, and the likelihood of FDA approval is increased by having a narrow indication. But here’s the irony: the narrower the indication, the less chance the company will ever recoup its money.
And there is a fundamental
problem with imaging substances in general. Contrast agents are regulated just
like drugs: the same standards apply for a contrast agent as for an antibiotic
used to treat a life-threatening infection. Apparently it takes an act of
Congress to get contrast agents regulated differently from drugs, and so far
that hasn’t happened. But it’s obvious that there need to be different rules
for approving imaging agents. Just another disgrace. Add it to the list.
What a crock! A normal lymph
node for somebody with breast cancer is no different than a normal lymph node
for somebody with prostate cancer. Combidex is “taken up” only in normal
tissue. If the tissue’s not normal, the contrast agent is not taken up, and you
know there’s cancer.
So while it would appear that
applying for a broad application not only made medical sense, it was the only
hope Ad Mag had of getting their money back.
There’s a lot more to the death
of Comidex. You’ll find it in two chapters of our book: Chapter 15, “Now
Playing for a Limited Time Only: The Combidex Follies,” and more in Chapter 17,
“Anatomy of an Assisted Suicide.”
I admit it. I’m pretty much
obsessed with the fate of Combidex. But as some French person once said, Rien ne vaut un bon obsession . . . (“There’s
nothing as valuable as a good obsession.”) And now I’ve found an ally (See
prior Combidex blogs) in the
courageous Prof. Jelle Barentsz
Combidex redux!
Labels:
Combidex,
FDA,
Jelle Barentz,
Jerome Goldstein,
ODAC
Tuesday, December 4, 2012
The Science Behind Active Surveillance
BY MARK SCHOLZ, MD
Active Surveillance versus the “Gold Standard”
Ten years ago surgery was called the “Gold Standard,” the treatment to which every other kind of treatment should be compared. Now you rarely encounter the Gold Standard argument to bolster surgery as the preferred treatment approach. What scientific studies led to this change in perspective and why has it taken so long for this change to come about?
Finally, a Clear Answer
The final nail in the “Gold Standard” argument occurred in 2012, when the New England Journal of Medicine published a study by Dr. Timothy Wilt comparing the long-term outcome of surgery versus observation.1 Between 1994 and 2002, seven hundred and thirty-one men volunteered to undergo either surgery or observation based on a coin flip.
Even before Dr. Wilt’s report was published, Active Surveillance had been gaining mainstream acceptance in the medical community. Multiple, independently-published studies consistently reach the same conclusion that Active Surveillance is safe. Some of these studies are briefly summarized in the next few paragraphs. The full abstracts are posted on our website at www.keepmyprostate.com.
Active Surveillance versus the “Gold Standard”
Ten years ago surgery was called the “Gold Standard,” the treatment to which every other kind of treatment should be compared. Now you rarely encounter the Gold Standard argument to bolster surgery as the preferred treatment approach. What scientific studies led to this change in perspective and why has it taken so long for this change to come about?
Finally, a Clear Answer
The final nail in the “Gold Standard” argument occurred in 2012, when the New England Journal of Medicine published a study by Dr. Timothy Wilt comparing the long-term outcome of surgery versus observation.1 Between 1994 and 2002, seven hundred and thirty-one men volunteered to undergo either surgery or observation based on a coin flip.
No
Benefit for “Good” Cancer, Modest Benefits for “Bad” Cancer
The average age for the whole group of
men was 67. The median PSA was 7.8. The study ultimately concluded that here
was no difference in prostate cancer mortality with either approach. Mortality
was within the expected range of statistical variation (5.8% died in the
surgery group and 8.4% died in the observation group). A small survival benefit for surgery was seen
in men with a PSA over 10. (Mortality
was 12.8% in the observation group and 5.5% in the surgery group.) Dr. Wilt
also reported the side effects of surgery.Even before Dr. Wilt’s report was published, Active Surveillance had been gaining mainstream acceptance in the medical community. Multiple, independently-published studies consistently reach the same conclusion that Active Surveillance is safe. Some of these studies are briefly summarized in the next few paragraphs. The full abstracts are posted on our website at www.keepmyprostate.com.
Do All
Men Have Prostate Cancer?
One of the most compelling arguments
for forgoing radical treatment is based on the fact that prostate cancer is
simply too common in the general population to represent an imminent threat to
life. Studies of prostate glands removed from men dying of unrelated causes
show that by the time they die, most men harbor prostate cancer.1
That prostate cancer is incredibly common in the normal male population is also
supported in another report from the New
England Journal of Medicine where 4,692 healthy men over age 50 with a
normal PSA (average 2.7) volunteered to undergo a simple six-core prostate biopsy.
The resulting biopsies showed that one-fourth
of the men had cancer.2
Many
Studies, Same Conclusion
Additional research has looked into
comparing Active Surveillance with surgery. For example, a study from Johns
Hopkins reported that life expectancy is only extended an average of 1.8 months
by having immediate surgery.3 Another
study in the Journal of Urology
confirms that the grade of the tumor
is an excellent method for determining which type of cancer is safe to monitor
because prostate cancer mortality was almost nonexistent in 12,000 men with Gleason
score of six or less who were monitored
for 12 years after surgery.4
Additional
studies reporting the long-term outcome of Active Surveillance have been
published: In a ten-year study of 1,000 men undergoing observation at Johns
Hopkins Hospital, not a single man has died of prostate cancer or developed
metastases.5 In another study of 450 men undergoing observation in
Toronto that included some men with grade 7 disease, five out of 450 men died
of prostate cancer.6
The
Dark Side of Treatment
The idea of living with cancer may not
seem at all attractive, but once the side effects of surgery are factored in,
Active Surveillance starts to look really good. Unfortunately, the side effects
of radical treatments like surgery are universally underemphasized by doctors
and patients alike. Doctors downplay the effects of surgery because their years
of working in the field accustom them to impotence and incontinence in their
patients. The patients who have had treatment and are lucky enough to have had
a good outcome, sing the praises of treatment because they took a radical step
to remove their cancer and were fortunate to avoid bad consequences. The
patients with bad outcomes are frequently too embarrassed to talk about their
diapers and sexual incapacity. They
minimize the bad effects of the treatment and emphasize their gratefulness
about “having been saved from cancer.”
The
fact is that surgery and radiation cause permanent side effects with astounding
frequency. In a study of 475 men, four
years after having surgery or radiation, less than 20% of men described their
sexual function as returning to normal.7 In another study of 785
men, three years after surgery or seed implantation, less than 20% of men who
had surgery and less than 50% of the men who had seeds described their sexual
function as returning to normal.8 Unfortunately, to many people, all
these statistics are an abstraction. Nevertheless, the tragedy of unnecessarily destroying even one man’s
sexual identity cannot be calculated.
At
First, New Thinking Always Seems Radical
Let me close with an acknowledgement
that Active Surveillance involves a totally new way of thinking. The very first
conference to review the science of Active Surveillance was convened in San
Francisco in 2007. At that time two hundred prostate cancer experts laid down
the basic guidelines for Active Surveillance.
Doctors around the world are still being introduced to the idea of Active
Surveillance. Believe it or not, some doctors have not even heard about
it. Inevitably, it takes time for people
to change. Even so, that’s no reason for you to be trapped by outdated thinking.
Labels:
active surveillance,
Dr. Timothy Wilt,
gleason 7,
gold standard prostate cancer,
John Hopkins,
New England Journal of Medicine,
overtreatment,
surgery
Tuesday, November 27, 2012
Life After Combidex - Part 2
BY RALPH BLUM
If after my long association with prostate cancer, I could achieve one objective—strike one blow for all the thousands of men facing the uncertainty of lymphatic involvement—it would be to see the presently FDA scorned and excommunicated compound “Combidex,” restored to favor, in production and universally available for the Combidex MRI.
If after my long association with prostate cancer, I could achieve one objective—strike one blow for all the thousands of men facing the uncertainty of lymphatic involvement—it would be to see the presently FDA scorned and excommunicated compound “Combidex,” restored to favor, in production and universally available for the Combidex MRI.
This contrast fluid consists of minute Fe nanoparticles (iron particles) that
are injected into a vein in the arm. After 24 hours, metastases in lymph nodes
(LN) that show less “uptake” of the iron oxide nanoparticles, are visible as a
white structure in a dark background, whereas normal nodes display as black and
are thus not distinguishable. The white metastatic lymph nodes light up like light
bulbs in the darkness, and can hardly be missed by the radiologist.
I do my due diligence: regular PSAs. But
lately, I have been anxious; concerned that my immune system is no longer doing
its job as well as it did in the past. True, I have no compelling evidence that
my cancer is “on the move,” changing color by Mark’s Blue Scale, edging from
“Sky” to “Teal” to “Azure”, with each deepening “Shade” bringing
heightened “Risk.” And yet sometimes in
the night I wonder: Is that a swelling I
feel in certain lymph nodes?
What makes this a period of greater insecurity
is the absence of my old ally “Combidex”.
It wouldn’t be that difficult to set my mind at ease about whether or not
there is lymphatic involvement if, as I did five years ago, I could again take
myself off to the clinic of Dr. Jelle Barentsz, Professor of Radiology at
Radboud University in Nijmegen, The Netherlands, and undergo a Combidex MRI.
There are other tests available. But from what
I’ve seen of the stats, either they don’t do the job the way Combidex did, or
more research is required. Still, here are four you might want to check out. I
confess that I am out of my depth here, reporting as a non-medical voice
without pretension of authority or a guarantee of accuracy:
1. 11C Choline PET CT while
effective to a point, is not good in detecting nodes <5 mm. In this regard, Combidex
was clearly superior.
2. Feraheme (ferumoxytol) is not as
effective going to normal nodes as Combidex, and thus has a significantly
higher number of false positives! Anyone who uses this agent for nodal imaging
should be aware of this, So again, this substance is not a good substitute for
Combidex.
3. The new Prostascint Imaging (Indium-111: Labeled Capromab Pendetide) which shows
promise (it is more specific PSMA) but is still in its early phases of testing.
Indications are that Prostascint may be useful to evaluate
post-prostatectomy patients with rising PSA who have an otherwise negative or
equivocal workup for metastases. Another potential role for Prostascint
(controversial) is in the staging of newly diagnosed prostate cancer.
What is worth doing? My mind is preoccupied
with thoughts of risk (doing nothing) versus trauma (the ghastly side effects).
I have long thoughts about the “velocity of change.” I meditate about risk versus trauma. And I pine for
Combidex.
Perhaps my Better Angels have been on the job.
Because just as I finished this blog, I received a note from Dr. Barentsz in
the Netherlands, informing me that maybe—just maybe—Combidex is about to stage
a come back. And asking for my help. Did he ever come to the right man! I will
lay out the strategy in my final “Life After Combidex” blog.
Hot dog! Combidex redux!
Labels:
C 11 PET,
Combidex,
Feraheme,
Jelle Barentsz,
MD,
ProstaScint,
prostate cancer,
PSA
Tuesday, November 20, 2012
Provenge Treatment for Prostate Cancer
BY MARK SCHOLZ, MD
In
2010, Provenge was approved by the FDA, the first approved prostate cancer
treatment that functions by enhancing the immune system. Over the last
couple of years Provenge has been gaining
popularity with oncologists and urologists as well as with patients. What has
been surprising to me is how slowly doctors and patients have warmed up to the
idea of using the immune system to fight prostate cancer. For years my
patients have been taking handfuls of Graviola, Shitaki mushrooms, Pau de Arco
and Esiac tea because of unsubstantiated claims of immune enhancement. Yet, when
the FDA approved an effective immune treatment that prolongs life I was
surprised that my patients needed to be convinced to use it.
Why, you might ask, is there any hesitation in the first
place? Well, Provenge is certainly different from other anticancer
therapies at least in one very distinctive way: Whereas the effectiveness
of most treatments is signaled by a drop in PSA, PSA levels usually don’t
decline after Provenge. Having supervised more than a hundred
Provenge-treated men, I have certainly seen exceptional cases with dramatic PSA
declines. However, this is not the general rule. Most of the time PSA continues
rising after Provenge. So people start wondering, if PSA is not dropping, how
can Provenge prolong survival? People forget that even though Provenge is
administered over a six-week period, once the immune system is activated, it
keeps functioning indefinitely; it’s the gift that keeps giving for the rest of
your life. Therefore, even if Provenge only slows disease growth
slightly, the inhibitory effect keeps accumulating over time. So over a period
of years, even a mild effect can become substantial.
If
the hypothesis that Provenge is inducing a mild, long-lasting anticancer effect
is correct, men take Provenge at an earlier stage (who have a longer projected
survival) should receive a bigger survival benefit than men treated at a later
stage. To test this thought, Dendreon, the manufacturer of Provenge, analyzed
data from the original studies that led to FDA approval. Please note: the researchers did not compare the survival
of men treated earlier versus the survival of men treated later.
Obviously, men treated at an earlier stage live longer. No, what they did
is compare survival of Provenge-treated men with earlier-stage disease with
similar-stage placebo-treated men. They did the same analysis
(Provenge-treated men versus placebo-treated men) in men with later-stage
prostate cancer and in men with disease “in between” early and late
stage. Early stage—low-intermediate stage, high-intermediate stage and
late stage—was defined by PSA levels of less than 22, 22-50, 50-134, and
greater than 134 respectively. The table below summarizes the results of their
analysis.
|
Patients
Grouped by Baseline PSA
|
|||
≤22
|
22– 50
|
50–134
|
>134
|
|
Number
patients
|
128
|
128
|
128
|
128
|
Survival
months:
|
|
|
|
|
Provenge
|
41.3
|
27.1
|
20.4
|
18.4
|
Placebo
|
28.3
|
20.1
|
15.0
|
15.6
|
Survival
Difference:
|
13.0
|
7.1
|
5.4
|
2.8
|
As
can be seen from the table, all groups that were treated with Provenge showed a
survival advantage compared to the same stage men treated with placebo.
However, when Provenge was given at an earlier stage, the survival advantages
became larger. Men with the earliest stage (PSA < 22) lived 13 months
longer than similar stage men who were placebo-treated. Men with advanced
stage only lived a couple months longer than advanced-stage placebo-treated
men.
This
pattern of improved survival with earlier stage disease seems to fit the
hypothesis that the inhibitory effect of Provenge results in a progressively
longer survival when its effects are allowed to
accumulate over a longer lifespan. Based on this data one would logically
conclude that Provenge induces the biggest benefits when administered at the
earliest possible stage. In the real world, where Provenge is only
covered by insurance for men who are hormone resistant and have metastases, men
on Lupron who have a rising PSA should be vigilantly monitored with scans such
as Prostascint, C11 acetate PET and Sodium Fluoride PET scans every 6 months to
detect metastatic disease at the earliest possible stage.
Labels:
c11 acetate PET,
immune therapy,
ProstaScint,
prostate cancer,
provenge,
PSA,
sodium fluoride PET
Tuesday, November 13, 2012
Life After Combidex (Part 1)
BY RALPH BLUM
In 2007, when my Gleason score had gone from 6 to 7 and the cancer had arrived in the left seminal vesicle, I traveled to theNetherlands for a Combidex MRI. According to the makers, Advanced Magnetics, Inc. (now AMAG Pharma), Combidex, the brand name for ferumoxtran-10, could “assist in the differentiation between metastatic and non-metastatic lymph nodes in patients with confirmed primary cancer who were at risk for lymph node metastasis.” How it worked was that metastatic lymph nodes showed less “uptake” of the iron oxide nanoparticles. Fortunately for me, all my lymph nodes were clear. However (and it’s a long story that I detailed in Invasion of the Prostate Snatchers) the Combidex infusion MRI, by far the most reliable (better than 90% accurate) diagnostic test for lymph node detection, didn’t make it past the FDA watchdogs, and AMAG Pharma discontinued the production of ferumoxtran-10. So the Combidex MRI is presently no longer available anywhere.
The primary FDA-approved diagnostic test for detecting lymphatic involvement is the ProstaScint scan. Given by an intravenous injection, ProstaScint circulates throughout the body and attaches to prostate cancer cells. The injection contains a small amount of low-level radioactive material that is absorbed by the cancer cells and shows up as “hot spots.” But the findings are subtle, with a high risk of false positives, and an absolute necessity with the ProstaScint scan is an extremely experienced interpreter.
Meanwhile inHolland , Dr Jelle Barentsz, Professor of Radiology, UMC St. Radboud, Nijmegen , has been working on a validation study of Feraheme (made of nano-particles of iron) as a lymph node diagnostic agent. Feraheme is the contrast agent with which AMAG Pharma replaced Combidex, and Dr. Barentsz’ study is to find out if Feraheme is as good a contrast agent as Combidex. Currently Feraheme is only approved for treating patients with iron deficiency anemia or chronic adult kidney disease.
A few days ago I got an email bemoaning the demise of Combidex, and asking for a review of the situation, including what replacements were on the horizon. So in this Blog and the next, I will attempt to shed some light on the matter.
The most common areas of prostate cancer metastasis are the pelvic or abdominal lymph nodes and the bones, but detecting whether the cancer has spread to the lymph nodes is a problem, because no truly reliable diagnostic test for lymphatic involvement is currently available.
In 2007, when my Gleason score had gone from 6 to 7 and the cancer had arrived in the left seminal vesicle, I traveled to the
The primary FDA-approved diagnostic test for detecting lymphatic involvement is the ProstaScint scan. Given by an intravenous injection, ProstaScint circulates throughout the body and attaches to prostate cancer cells. The injection contains a small amount of low-level radioactive material that is absorbed by the cancer cells and shows up as “hot spots.” But the findings are subtle, with a high risk of false positives, and an absolute necessity with the ProstaScint scan is an extremely experienced interpreter.
Meanwhile in
We desperately need better tests. The ability of oncologists to accurately detect lymph node involvement could signify a huge step forward in staging and, therefore, in making optimal treatment decisions for men with newly diagnosed and advanced prostate cancer.
Labels:
AMAG Pharma,
Combidex,
Feraheme,
gleason,
Invasion of the Prostate Snatchers,
Jelle Barentsz,
lymph nodes,
MRI,
Netherlands,
ProstaScint,
prostate cancer
Thursday, November 8, 2012
A Breakthrough Study in Prostate Cancer
BY MARK SCHOLZ, MD
Ten years ago everyone agreed that surgery was the “Gold Standard” to which every other kind of treatment should be compared. Now as we approach 2013, you rarely encounter the Gold Standard argument to bolster surgery as the preferred treatment approach. What has led to the change in perspective and why has it taken so long for this change to come about?
Good Science Finally Leads to a Clear Answer
The primary cause for the changed perspective about surgery is the result of a well-performed scientific study published this year by Dr. Timothy Wilt in the New England Journal of Medicine. The study has been a long time coming. It was first conceived way back in the early 1990s when Dr. Wilt and others designed a definitive trial to test whether or not radical prostate surgery improves survival compared to observation. Even back then, researchers knew that prostate cancer can often behave benignly and were questioning the benefits of radical surgery. Therefore, between 1994 and 2002 over five-thousand men were invited to participate in a study comparing immediate surgery with no treatment. To make the comparison totally fair, individuals volunteering for the study had to be willing to have either surgery or observation based on the flip of a coin. Most of the more than five thousand men who were invited to participate in the study refused. Ultimately, however, 731 men agreed to participate.
Modest Benefits for “Bad” Cancer, No Benefit for “Good” Cancer
At the start of the study the average age of the men participating was 67 and the median PSA was 7.8. After ten years the difference in prostate cancer mortality was essentially the same in both groups, i.e., within the expected range of statistical variation: 5.8% died in the surgery group and 8.4% died in the observation group. However, subgroup analysis of the 251 men in the study who started off with PSA levels above 10 showed a modest improvement in survival for the men undergoing surgery: 5.5% died in the surgery group and 12.8% died in the observation group.
Validation of the Right Way to Look at Prostate Cancer
This picture of how different types of prostate cancer behave over long periods of time (having a high PSA for example versus having a low PSA) has been slowly forming in the minds of the prostate cancer experts over the years. Dr. Anthony V. D’Amico, MD, PhD, Professor of Radiation Oncology at Harvard Medical School, is credited with developing the modern staging system that divides men into Low, Intermediate and High-Risk categories (At the PCRI we call them Shades of Blue, i.e., Sky, Teal and Azure). Dr. Wilt’s study conclusively validates the fact that favorable prostate cancer—termed Low-Risk—can be safely monitored without immediate treatment, whereas men with High-Risk disease derive a modest benefit from immediate treatment. His study also reported an intermediate outcome for the men with Intermediate-Risk disease: After 10 years, men in the Intermediate category showed no improvement in cancer survival with surgery. However, there was a 10% lower incidence of metastases in the men with Intermediate-Risk who had surgery.
Conclusion
Dr. Wilt’s study is an important breakthrough because it is the first modern, large, long-term, prospective, randomized study comparing treatment versus no treatment in men with relatively early-stage disease, i.e. diagnosed via PSA screening. This study provides critically important scientific confirmation validating the policy of withholding radical treatment in men with Low-Risk disease. The study also validates the predictive accuracy of the D’Amico staging system which functions by dividing men into Low, Intermediate and High-Risk categories. Lastly, Dr. Wilt’s study provides a quantifiable measure of the degree of benefit associated with immediate surgery in men with Intermediate-Risk and High-Risk disease. Using this information, individuals with High-Risk disease can better understand the rather modest survival advantages of surgery, and weigh them against the probable deleterious side effects, enabling them to determine for themselves whether or not they want to proceed with radical treatment.
Labels:
D'Amico,
Dr. Timothy Wilt,
Gold Standard,
New England Journal of Medicine,
prostate cancer,
prostate surgery,
PSA,
Shades of Blue
Tuesday, October 30, 2012
Revisiting TIP (Testosterone Inactivating Pharmaceuticals)
BY RALPH BLUM
Why Does TIP Work?
Testosterone is the hormone that causes boys to become men at puberty. Prior to puberty, the prostate gland is roughly the size of a small marble. Then, when the teenage surge of testosterone occurs, the gland expands to walnut size and begins producing semen. This transformation occurs because the cells of the prostate gland are uniquely sensitive to the presence, or absence, of testosterone. Lowering the level of testosterone in the blood causes the cancer cells to shrivel up a die because the cancer cells are derived from prostate gland cells and retain the same dependence on testosterone for survival.
Long Term Results
One downside to TIP is that while it shrinks the cancer, it does not, ultimately, kill every last cell. However, it has been my treatment of choice for the past ten years. Studies done at Prostate Oncology Specialists, Inc. show that after twelve months of TIP the amount of residual cancer is usually too small to be detected with a lesion-directed biopsy using color Doppler ultrasound. In most cases PSA drops to near undetectable levels (mine dropped to 0.125), and TIP has the added benefit of having anti-cancer effects throughout the body.
When TIP is stopped, testosterone levels gradually return to normal, and a number of men require no further treatment. Some men require periodic treatment with TIP to keep their PSA levels under 5. And other men, rather than continuing with intermittent TIP, decide to go for surgery, seeds or IMRT. However, even this latter group has bought themselves on average of five plus years before risking the intimidating potential side effects of more radical treatments.
Side Effects of TIP
Although no prostate cancer treatment is free of undesirable side effects, most of the side effects of TIP (weight gain, muscle loss, loss of libido) are preventable with proper management. And loss of libido, unlike impotence, is reversible when TIP is stopped. Meanwhile, although some of the magic may be gone while on TIP, most men find that they can still enjoy sex (and give pleasure to their partners) with a little help from Big Pharma. Viva Viagra!
Testosterone is the hormone that causes boys to become men at puberty. Prior to puberty, the prostate gland is roughly the size of a small marble. Then, when the teenage surge of testosterone occurs, the gland expands to walnut size and begins producing semen. This transformation occurs because the cells of the prostate gland are uniquely sensitive to the presence, or absence, of testosterone. Lowering the level of testosterone in the blood causes the cancer cells to shrivel up a die because the cancer cells are derived from prostate gland cells and retain the same dependence on testosterone for survival.
Long Term Results
One downside to TIP is that while it shrinks the cancer, it does not, ultimately, kill every last cell. However, it has been my treatment of choice for the past ten years. Studies done at Prostate Oncology Specialists, Inc. show that after twelve months of TIP the amount of residual cancer is usually too small to be detected with a lesion-directed biopsy using color Doppler ultrasound. In most cases PSA drops to near undetectable levels (mine dropped to 0.125), and TIP has the added benefit of having anti-cancer effects throughout the body.
When TIP is stopped, testosterone levels gradually return to normal, and a number of men require no further treatment. Some men require periodic treatment with TIP to keep their PSA levels under 5. And other men, rather than continuing with intermittent TIP, decide to go for surgery, seeds or IMRT. However, even this latter group has bought themselves on average of five plus years before risking the intimidating potential side effects of more radical treatments.
Side Effects of TIP
Although no prostate cancer treatment is free of undesirable side effects, most of the side effects of TIP (weight gain, muscle loss, loss of libido) are preventable with proper management. And loss of libido, unlike impotence, is reversible when TIP is stopped. Meanwhile, although some of the magic may be gone while on TIP, most men find that they can still enjoy sex (and give pleasure to their partners) with a little help from Big Pharma. Viva Viagra!
Final Thoughts
I can think of only three reasons why this non-invasive alternative to surgery and radiation is not more often the treatment of choice for men with Intermediate-Risk prostate cancer:
1) Patients never hear that it is an option: Urologists usually don’t suggest TIP to men with Intermediate-Risk cancer as a viable alternative to their preferred treatments—surgery and radiation.
2) Doctors are unfamiliar with the TIP option. Finding an oncologist with experience in state-of-the-art methods of administering TIP is still a challenge.
I can think of only three reasons why this non-invasive alternative to surgery and radiation is not more often the treatment of choice for men with Intermediate-Risk prostate cancer:
1) Patients never hear that it is an option: Urologists usually don’t suggest TIP to men with Intermediate-Risk cancer as a viable alternative to their preferred treatments—surgery and radiation.
2) Doctors are unfamiliar with the TIP option. Finding an oncologist with experience in state-of-the-art methods of administering TIP is still a challenge.
3) Most men are shocked and fearful when they are first diagnosed with prostate cancer, and it’s hard to resist the emotional appeal of “Just cutting it out”—especially when the risks of more radical treatment are sometimes glossed over.
Thankfully, in 2002, when I learned that my PSA had bumped up to 18.3, my fear of being sliced open, or fried by radiation led me to Mark Scholz, and TIP. And although I would not describe my experience as “a day at the beach,” I am deeply grateful that I chose TIP, and, more importantly, ten years later, I am still here!
Labels:
color Doppler ultrasound,
intermediate risk prostate cancer,
prostate oncology specialists,
PSA,
radiation,
side effects,
surgery,
Testosterone Inactivating Pharmaceuticals,
TIP,
urologists
Tuesday, October 23, 2012
The Un-Cancer
BY MARK SCHOLZ, MD
It’s easier to teach a proper golf swing to a true beginner than to someone who has previously developed bad habits that are now ingrained. The young mind of a child learns a new language much more easily than the cluttered mind of the adult. Good first impressions are valued so highly because we all know how hard it is to undo a bad first impression. The biggest challenge of educating people about prostate cancer is overcoming their preconceived notions—what they already think they know about cancer.
What is prostate cancer? Many say it’s harmless, that “you die with it, not from it.” But how does that jibe with 28,000 deaths annually? One reasonable conclusion is that prostate cancer occurs and acts in a variety of different ways. The Prostate Cancer Research Institute (pcri.org) recommends dividing prostate cancer up into five categories or Shades of Blue. This is helpful both for understanding the varieties of prostate cancer and for guiding the choice of treatment.
However, even though there are many forms of prostate cancer, this fact fails to convey how differently prostate cancer as a whole acts, compared to other cancers. Why is it so important to understand this difference? First of all, surgery—which is everyone’s first thought when they hear the word “cancer”—can have dire consequences. For example, surgery almost always causes partial or complete impotence. Second, new research published by Dr. Timothy Wilt in the July issue of this year’s New England Journal of Medicine, shows that forgoing immediate treatment and embarking on a program of close monitoring known as “active surveillance,” has exactly the same survival rate as immediate surgery. Bottom line: For far too many men, immediate treatment for prostate cancer is not only damaging, it is often unnecessary.
Forgoing treatment with something called cancer is certainly counterintuitive. In order to support the case for monitoring, let’s compare the statistics for prostate cancer with those of colon cancer.
As the table shows, men diagnosed with colon cancer are not only three and a half times more likely to die from the disease, they die twelve times more quickly. Unfortunately, almost all cancers—lung, pancreas, stomach, gallbladder, kidney, brain, bone, etcetera—approximate the behavior of colon cancer rather than prostate cancer.
It’s easier to teach a proper golf swing to a true beginner than to someone who has previously developed bad habits that are now ingrained. The young mind of a child learns a new language much more easily than the cluttered mind of the adult. Good first impressions are valued so highly because we all know how hard it is to undo a bad first impression. The biggest challenge of educating people about prostate cancer is overcoming their preconceived notions—what they already think they know about cancer.
What is prostate cancer? Many say it’s harmless, that “you die with it, not from it.” But how does that jibe with 28,000 deaths annually? One reasonable conclusion is that prostate cancer occurs and acts in a variety of different ways. The Prostate Cancer Research Institute (pcri.org) recommends dividing prostate cancer up into five categories or Shades of Blue. This is helpful both for understanding the varieties of prostate cancer and for guiding the choice of treatment.
However, even though there are many forms of prostate cancer, this fact fails to convey how differently prostate cancer as a whole acts, compared to other cancers. Why is it so important to understand this difference? First of all, surgery—which is everyone’s first thought when they hear the word “cancer”—can have dire consequences. For example, surgery almost always causes partial or complete impotence. Second, new research published by Dr. Timothy Wilt in the July issue of this year’s New England Journal of Medicine, shows that forgoing immediate treatment and embarking on a program of close monitoring known as “active surveillance,” has exactly the same survival rate as immediate surgery. Bottom line: For far too many men, immediate treatment for prostate cancer is not only damaging, it is often unnecessary.
Forgoing treatment with something called cancer is certainly counterintuitive. In order to support the case for monitoring, let’s compare the statistics for prostate cancer with those of colon cancer
Prostate Cancer:
The “Un-Cancer”
|
A “Typical” Cancer
|
Difference
Factor
| |
Deaths Annually
|
28,000
|
26,000
|
1 : 1
|
New Cases Diagnosed
|
241,000
|
73,000
|
3.5 : 1
|
Mortality Rate
|
8.5%
|
35.5%
|
4.2 : 1
|
Average Survival if Relapse Occurs
|
13 Years
|
13 Months
|
12 : 1
|
The fact remains that it is logical for the general population to be terrified by the very idea of cancer. When you consider all the different types combined, cancer is the second most common cause of death, just below heart disease. The risk of death from most cancers is high and if a cure is not obtained, death follows all too quickly. The unfortunate men who die from prostate cancer make the “news,” even though it may not be generally understood that it took 13 years for those men to succumb. However, the fact remains that there are 2.8 million prostate cancer survivors presently living in the U.S. That should be news too.
Ninety-one and a half percent of men diagnosed with prostate cancer will have a normal life expectancy, and will die of natural causes. The eight and a half percent who die from prostate cancer will live an average of 13 years, with this number expected to increase dramatically over the next ten years, thanks to continuing improvements in medical technology. Treatment can definitely improve survival in selected cases. However, it would seem that only men in the high-grade category are likely to benefit consistently.
The encouraging facts about prostate cancer outlined in this blog have been compiled to help men realize that survival rates with prostate cancer are extremely favorable compared to other types of cancer. Now that studies show that survival with active surveillance matches that of immediate surgery, a great many men should take heart, and resist all efforts to rush into a treatment with such uncertain rewards but such predictable and devastating side effects.
Labels:
Blue Community,
colon cancer,
Dr. Timothy Wilt,
heart disease,
New England Journal of Medicine,
PCRI,
prostate cancer,
surgery
Tuesday, October 16, 2012
Harmony & Spirituality Practice Cultivating “Wa”
BY RALPH BLUM
When discord hobbles me, throws off my vital signs, fogs up my reasoning, I feel it has a definite impact on my immune system. Efforts to counter mindless anxious behavior through breathing and light meditation may help, but in my case, only minimally. Instead, whenever I encounter discord, or more to the point, when I catch myself creating or contributing to the dissonance, I retreat from that discord as fast as I can. This happens in three steps:
First, I catch myself, recognize what’s happening, mark the moment: Blum, you’re doing it!
Second, I apply the brakes, stop what I am doing as best I can. Do whatever it takes to get into reverse and back away. I think of this step as “circuit breaking.”
Third, I substitute different behavior, consciously find a better way to look at what is disturbing my peace and serenity, my wa.
Example: Despite my expectations, my PSA has risen. And I’m suddenly scared s—tless my next Gleason score will have deteriorated from 3 + 3 to 3 + 4, and that I will start feeling pressure to “act,” to begin radical treatment. As a Remedy, I hold a conversation with myself,
Me: How many years has your cancer been in the seminal vesicle?
Myself: About six.
Me: So six years out of the capsule?
Myself: Yup.
Me: Is the cancer in your bones?
Myself: No.
Me: Well, how about the lymph system?
Myself: Don’t think so.
Me: So And how old are you?
Many years ago, I was invited to attend a breakfast fund raising event at the Bel Air Hotel in West Los Angeles . Ted Turner was attempting to squeeze donations from a room full of Hollywood moguls. The private dining room was filled with sunlight, and I remember sitting there, bored, zoned out and forking segments of my eggs Benedict around, when Turner’s Savannah chain gang growl poked a hole in my reverie: “I tell you, it’s spiritual,” he exclaimed. “And you know how I know it’s spiritual? Because I paid cash money for it.”
To this day, I have no idea what “it” was. But Turner’s logic—his working definition of “spiritual”—made me smile and stuck with me to this day. And while I’d rather steer the long way around when it comes to spiritual matters in general, I have become a devoted fan of harmony, as in feeling at peace. What the Japanese call Wa. Bottom line: I try not to regret anything that has already happened, and not to worry about what might happen. And in a way, I think this has played a role in my coming to terms with prostate cancer.
When discord hobbles me, throws off my vital signs, fogs up my reasoning, I feel it has a definite impact on my immune system. Efforts to counter mindless anxious behavior through breathing and light meditation may help, but in my case, only minimally. Instead, whenever I encounter discord, or more to the point, when I catch myself creating or contributing to the dissonance, I retreat from that discord as fast as I can. This happens in three steps:
First, I catch myself, recognize what’s happening, mark the moment: Blum, you’re doing it!
Second, I apply the brakes, stop what I am doing as best I can. Do whatever it takes to get into reverse and back away. I think of this step as “circuit breaking.”
Third, I substitute different behavior, consciously find a better way to look at what is disturbing my peace and serenity, my wa.
Example: Despite my expectations, my PSA has risen. And I’m suddenly scared s—tless my next Gleason score will have deteriorated from 3 + 3 to 3 + 4, and that I will start feeling pressure to “act,” to begin radical treatment. As a Remedy, I hold a conversation with myself,
Me: How many years has your cancer been in the seminal vesicle?
Myself: About six.
Me: So six years out of the capsule?
Myself: Yup.
Me: Is the cancer in your bones?
Myself: No.
Me: Well, how about the lymph system?
Myself: Don’t think so.
Me: So And how old are you?
Myself: I’ve been around the sun 80 times.
Me: So in 10 years you’ll be 90?
Myself: You might look at it that way.
Me: And your cancer, basically untreated, has been stable for almost a quarter of a century.
Me: So in 10 years you’ll be 90?
Myself: You might look at it that way.
Me: And your cancer, basically untreated, has been stable for almost a quarter of a century.
Myself: Something like that.
Myself: So given hour history, what kind of prognosis would you expect for the years to come. . . ?
The Q and A continues until I find myself relaxing, counting my blessings. This sounds like pretty simple-minded stuff. But not getting caught in the quicksand of negative emotions or behavior that is toxic, just staying in the “here and now,” is a spiritual practice that helps maintain Wa. I do my best to stay in the present moment. But when I slip, ASAP after the fact I review what has happened. I replay what happened in my mind with different features, focus on a better way to handle it next time. And some day perhaps I’ll find out what spiritual stuff Ted Turner paid cash money for. And place an order for myself. A baseball team. An ocean going racing yacht. A date withJane Fonda. CNN. A day at the beach. . .
To each his own kind of Wa.
More to come.
More to come.
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