For many years now I have been hearing asbestos company lawyers argue "that
there is no medical benefit to the early detection of malignant mesothelioma."
Below is an excerpt from a speech recently given by a prominent asbestos
company defense lawyer at an asbestos lawyers conference in Boston. To quote:
"No studies have been done which establish any benefit to finding
pleural or peritoneal mesotheliomas at an early stage. The 'evidence'
is largely anecdotal and varies widely from one individual to another.
Because the tumors are typically found only after they have spread, and
are incurable even if they are discovered while the patient is symptom-free,
early detection has virtually no medical benefit."
The statement is disturbing for a number of reasons.
First, there is something ghoulish about a lawyer for a company that has poisoned
people advocating that there is no need to monitor the health effects
caused by their poison. The attitude seems to be: yes, we made a poison
that invaded the lungs of many innocent people, but there's no proven
way to combat or prevent the bomb from exploding, so let it be and let
us alone. Doctors have a duty to "do no harm." I wish lawyers
were guided by the same credo.
Second, the statement is debatable at best and misleading at worst (see below).
There may not be any definitive studies out there which establish a clear
benefit, but there are plenty of studies which affirm that early detection
is vital because it allows the patient to choose from more treatment options.
At the "individual" level, what is more important to the patient
than having the power to select from multiple choices? Drs. Sugarbaker,
Pass, Rusch et al have published articles which support the thesis that
certain MM patients have a better prognosis when diagnosed early and treated
by multi-modal therapy -- and few doctors will recommend extrapleural
pneumonectomy or pleurectomy / decortication if the tumor has trespassed
the visceral pleura into the mediastinum, diaphragm, and/or lymph nodes.
Third, the "incurability" argument is tainted by conflict of interest.
The asbestos companies have shelled out millions of dollars to disprove
that asbestos causes cancer, but they have not spent a dime to find a
cure. In this world, you have to give action to get action. A wrongdoer
has a duty to mitigate the damage he inflicts. Instead of paying high
priced lawyers to excuse their misconduct, they ought to be funding research
on finding tumor markers, vaccines, immunotoxins and other therapies.
AIDS was also considered "incurable" ten years ago. Now, after
millions have been spent to find a cure, AIDS patients have a real chance
at survival. Same for breast cancer.
Fourth, the "incurability" argument hinders the ability of patients
to obtain aggressive and innovative therapy. Insurance carriers these
days are exceedingly reluctant to cover any medical procedure that is
considered "experimental." There are a handful of surgical oncologists
in this country who are truly dedicated to helping mesothelioma patients
survive and find a cure. I have had clients who arranged to meet with
these experts, but at the last moment their insurance carrier denied coverage
and ordered them to see a non-expert who offered only palliative care
or no care at all. The HMOs are still entrenched in the "death management"
mind set for mesotheliotics. This is a vicious circle -- there won't
be a cure if we don't fund the research and without the research the
insurance industry will continue to refuse to cover innovative therapies.
It's also a tragedy.
Fifth, the consensus among the doctors I correspond with is that if there are
"no studies," it is because nobody has every tried to create
an early detection program, fund it, implement it, and publish the results.
Most mesothelioma patients are NOT detected in the early stages -- sometimes
because general doctors fail to read the signs. Moreover, it's not
clear exactly what "early stage" means, as even at Stage I a
patient with a 1 cm tumor can have 500 million tumor cells active and
growing. Most mesotheliomas -- approximately 80% -- can be detected from
CT scans and chest films, along with a clinical picture (weight loss,
shortness of breath, pain in shoulder, pleural effusion, asbestos exposure
history). Multi-modal extrapleural pneumonectomies are certainly expensive
in dollar terms. The goal should be to a find a cookbook variety screening
test that would obviate the need for "radical" approaches.
The key is to give people in high risk populations (e.g., shipyard, steel
mill, paper mill, petrochemical plant workers, insulators) a choice. For
example, Dr. Robert Cameron has discussed the possibility of a "prophylactic
ablation" for high risk patients. The idea is that mesothelioma can
only arise in malignant mesothelioma cells. What if we removed or destroyed
all the healthy mesothelial cells? A technique could be developed to use
photodynamic therapy to kill the mesothelial cells in the pleural space,
or perhaps inject an anti-tumor drug that would accomplish the same objective.
This would remove the soil so to speak for a possible tumor to grow. The
pleural linings would bond together and the impairment if any would be minimal.
Sixth, if we do nothing, we learn nothing. If we don't invest the research
dollars now and develop a wider range of treatment plans down the road,
we will never have a chance to find a cure. I think history has taught
us that with enough money, we can put a man on the moon. It takes will
and it takes money. The best and brightest are humming with great ideas
for gene therapy, immunotherapies, tumor-killing viruses, vaccines, "angiostatins
and endostatins" (which purportedly kill tumors by starving their
blood supply), interferon and PDT. In talking with doctors like Dr. Cameron
and Dr. Jablons, there is a real excitement over the possibility that
good therapies can be developed. But without a serious financial commitment
at the basic science level, doom and gloom will be a self-fulfilling prophecy.
We cannot rely on private enterprise to get it done. The drug companies
are driven by profits. They are not willing to invest the millions of
dollars it takes to develop and test a new drug when "only 4,000"
Americans die each year from mesothelioma. They look at the statistics.
The conventional thought is that in 30 to 50 years the incidence of disease
in America will be negligible (what about the rest of world where asbestos
is still being mined, milled and used?). They are not willing "to
fire up the vats" without better prospects of an upside. This is
not a money-making proposition. It's about doing the right thing.
That's why we should first look to the companies who are responsible
for the disease -- the asbestos companies -- and secondly to the US Government,
who allowed the companies to peddle their poison for far too long before
issuing its ban in the 1970s.
Since the tortfeasors have refused to voluntarily clean up their mess,
the solution is legislation. Congress ought to force the asbestos companies
to pay a surplus of every settlement or jury verdict dollar to a research
foundation. The government should match each dollar. The money can be
managed by a blue chip team of the best mesothelioma doctors, doctors
like Dr. Pass, Dr. Cameron, Dr. Sterman, Dr. Jablons, Dr. Taub, Dr. Ruckdeschel,
Dr. Sugarbaker, Dr. Rusch, Dr. Robinson and Dr. Hammar.
Towards this end, my firm by the year 2000 hopes to establish a Mesothelioma
Research Foundation. The goal of the Foundation will be to fund basic
science and clinical research in order to help expand the treatment options
available to mesothelioma patients. My first step will be to ask the asbestos
companies to come forward and pay their share. Next, I will ask our political
leaders to fashion a legislative solution. Along the way, I will ask the
plaintiff's bar for contributions.
The money is available. It's a question of will. The tobacco companies
just "invested" $40 million in television commercials to combat
proposed state and federal legislation that would have hindered their
ability to sell more cigarettes. We need to get started. We have known
-- including the US Government -- that asbestos causes lung cancer since
the 1940's. Here we are, almost 60 years later, and still the medical
community has largely a fatalistic attitude about mesothelioma.
We need to get started! It generally takes about 15 years to bring an experimental
drug out of the laboratory and into human patients. Only one in 1,000
compounds tested makes it into clinical safety trials in humans, and only
one in 20 of these are eventually approved by the FDA.
What's out there now? There is a phase III protocol using Onconase,
but I have not read anything truly uplifting (I wish I was wrong). I have
heard about a drug made by Bayer that is being tested with other chemotherapy
agents in Rochester, MN and San Antonio, Texas. The drug is called BAY
12-9566. The drug apparently had a favorable response in a mesothelioma
patient in a phase I study for a wide range of cancer patients (it is
not confirmed that the subject actually had mesothelioma). Bayer is considering
the idea of developing a "compassionate use program" for mesothelioma
patients. The drug will be tested in phase I trials for pancreatic and
small cell lung cancers in 1999. We encourage Bayer to open up the studies
to mesothelioma patients and hope that they will publish the results of
their phase I trials soon.
I sent the quote from the asbestos company lawyer to several doctors who
diagnose and treat mesothelioma patients.
Dr. Samuel Hammar,
Diagnostic Specialties Laboratory, Inc. Bremerton, Washington
Dear Mr. Worthington:
I am responding to your letter concerning "No Medical Benefit to Early
Detection of Mesothelioma." In general, I do not agree with that
statement but would state that it is difficult to detect mesotheliomas
at an early stage of the disease at the present time. If one could devise
a test in which you could identify mesotheliomas when the tumors were
in stage 1 or less in the anatomic staging scheme, I think that would
potentially result in more therapeutic options for patients with mesothelioma.
I am convinced that there are a group of patients with stage 1 mesotheliomas,
especially epithelial mesotheliomas, that significantly benefit from extrapleural
pneumonectomy or from radical parietal pleurectomy and visceral pleural
I am also of the opinion that as time goes on the biology of mesothelial
cells will become better understood which could lead to a test in which
mesotheliomas could be detected at a very early stage, specifically, a
stage before they became clinically detectable. What I have often wondered
about in mesotheliomas is whether a platelet-derived growth factor, a
factor produced in 1/4 - 1/3 of patients with epithelial mesothelioma
could be used as a way of early detection. It is not clear to me at what
point in time this growth factor appears, but if it could be detected
at a point where the tumor was not grossly visible or a point where the
tumor was just beginning, maybe it could be used as a marker of when a
patient should be given some type of therapy which might include chemotherapy,
radiation therapy or photo-ablative therapy.
The problem, as I see it, is that at the present time relatively few cases
of mesothelioma are detected at an early stage. This is probably due to
the fact that it take a significant amount of tumor to produce clinical
symptoms and because mesothelioma is not like a lung cancer that produces
a nodular mass and is therefore difficult to detect in standard radiographs
or CT scans. I am one who thinks that once a mesothelioma progresses past
anatomic stage 1 there are no treatment modalities that can halt the growth
of that tumor. When this occurs it is my opinion that more effort should
be spent in trying to keep the patient pain free than trying to cure him.
I would like to see more studies done at trying to detect tumor markers
of mesothelioma (perhaps serum markers) in people who were exposed to
asbestos that would result in the tumors being detected at a stage before
they were clinically apparent. If that was done, maybe those patients
could be treated in a way that resulted in a significant survival rate.
There are antibodies that are now being developed against certain cancers,
specifically lymphomas that seem to be able to cure the diseases in a
very short period of time with only minimal side effects. If a tumor marker
for a mesothelioma was found that was highly specific, I could envision
the same type of therapy working in mesotheliomas, specifically an antibody
tagged to radioactive iodine that would search out the mesothelial cancer
cells, attach to them and then kill them. As in lymphoma, you would have
to have something absolutely specific for cancerous mesothelial cells
that would do minimal harm to the normal mesothelium and to the body in general.
Samuel P. Hammar, M.D.
November 2, 1998
Dr. John C. Ruckdeschel
H. Lee Moffit Cancer Center, Tampa, Florida
Dear Mr. Worthington:
The statement that there was no benefit to early detection is technically
accurate, however, it is misleading. Very few centers treat mesothelioma
and there is very little existing literature codifying the long-term survival
of patients with surgically treated disease. All of us who are active
in treatment of the disease know that if it is found in a resectable state,
that a portion of those patients will be cured by an extrapleural pneumonectomy.
However, there have been no studies to date testing any technique for
this. I know that many of the former patients are under regular study,
but have nor seen any of the follow-up data on this serial analysis. As
you are painfully aware, these patients are mostly diagnosed late.
Consequently, I don't think there is any strong evidence to refute
the concept other than the common sense fact that the only curable patients
are those that we do find early. Best wishes.
John C. Ruckdeschel, M.D.
Professor of Medicine and Center Director
November 9, 1998
Dr. Robert Cameron
UCLA Medical School, Los Angeles, California
The absolute statement about no benefit to early detection is technicallly
true. No one has ever shown any benefit to early detection (of course
no one has ever really tried and mesothelioma once present is almost always
diffuse and for the most part currently rarely curable.).
However, a recent patient brings up an interesting sideline to this. If
patients are known to have high asbestos exposure, i.e., worked for Johns
Manville for 20 years, etc. does prophylactic removal of the pleura PREVENT
mesothelioma? This also has not been answered but makes sense in patients
who are at particularly high risk as "an ounce of prevention is worth
thousands of pounds of treatment."
Therefore in screening patients, perhaps high risk individuals should undergo
prophylactic pleurectomy to prevent the need for treatment of an normally
incurable disease. If we can develop new treatments (by the way, Bayer
has a new drug which looks promising although it has been used in only
one patient so far and we are looking into doing more with it) then screening
may become more important. Sorry I cannot refute the other lawyers statement
any better but unfortunately, we have not done a good job at scientifically
proving him wrong!!
November 18, 1998
Note: Dr. Cameron and his team of doctors/scientists at UCLA are working on
an experimental IL-4 toxin, as well as new angiogenesis inhibitors, which
UCLA hopes to put into clinical trials in the next year or so. They are
also hoping to obtain the Bayer anti-enzyme. Dr. Cameron performs the
pleurectomy / decortication procedure. His strategy is to preserve a healthy
lung because of the probability of recurrence in the other pleural cavity.
He compares the EPP to a radical mastectomy, which is no longer in favor.
Dr. Robert Taub
Columbia Medical School, New York City
The statement needs to be analyzed. It seems to refer to the inadequacy
of current methods of screening of high-risk populations for early detection
of mesothelioma; parallel arguments exist for lung cancer. It may also
be referring to the observation that surgery alone has not made a statistical
impact on the overall survival of mesothelioma patients.
This, however, is to be clearly distinguished from what happens in individual
cases who are diagnosed with tumor that is confined to a small, operable
area. Mesothelioma, bad as it is, is not synonymous with a death sentence
because not everybody with the disease dies from it; we need to focus
upon those who don't. Now that operative mortality is down to 6% or
less, we should not dismiss the intuitive likelihood that selected patients
who are both asymptomatic and operable and that have their tumor extirpated
have a better chance of living than if their tumor is not removed.
Also, the reports of long term survivors after multimodality (surgery,
chemo, radiation) treatment is encouraging. Thus, for individual patients
right now, we need to find our how best to identify those patients who
have the best chance of falling on the "tail" end of the survival curve.
Dr. Robert Taub
November 1, 1998
Dr. David Jablons
UCSF/Mt. Zion, San Francisco, California
We need to have a grass roots movement and like all things we need to get
some grant money to fuel the science to find a cure or at least better
therapies, early detection, etc.
It can and will be done. Let's make this happen! There is plenty of
money in these settlements and in the industry or through legislation
such that a small percentage (which would represent a major increase over
current funding) could be directed into research.
November 1, 1998
Abstract provided by
Dr. Lary Robinson:
Eur Respir J 1998 Oct; 12(4):972-81
Malignant pleural mesothelioma.
Boutin C, Schlesser M, Frenay C, Astoul P
Dept of Pulmonary Diseases, Hospital de La Conception, Marseille, France.
The incidence of malignant pleural mesothelioma (MPM) has risen for some
decades and is expected to peak between 2010 and 2020. Up to now, no single
treatment has been proven to be effective and death usually occurs within
about 12-17 months after diagnosis. Perhaps because of this poor prognosis,
early screening has incited little interest. However, certain forms may
have a better prognosis when diagnosed early and treated by multimodal
therapy or intrapleural immunotherapy. Diagnosis depends foremost on histological
analysis of samples obtained by thoracoscopy. This procedure allows the
best staging to the pleural cavity with an attempt to detect visceral
pleural involvement, which is one of the most important prognostic factors.
Although radiotherapy seems necessary and is efficient in preventing the
malignant seeding after diagnostic procedures in patients, there had been
no randomized phase III study showing the superiority of any treatment
compared with another. However, for the early-stage disease (stage I)
a logical therapeutic approach seems to be neoadjuvant intrapleural treatment
using cytokines. For more advanced disease (stages II and III) resectability
should be discussed with the thoracic surgeons and a multimodal treatment
combining surgery, radiotherapy and chemotherapy should be proposed for
a randomized controlled study. Palliative treatment is indicated for stage
IV. In any case, each patient should be enrolled in a clinical trial.
Dr. Harvey Pass
Karmanos Cancer Institute and Wayne State University, Detroit, Michigan
I agree with the message that you are trying to convey on the net regarding
the earlier detection of mesothelioma. In order to accomplish this, however,
there will need to be a collaborative effort uniting bench work and clinical
efforts between institutions which have (1) an interest in the disease
(2) ongoing expertise, not only clinically but at the bench and (3) insight.
For this disease, one needs a consortium of centers which will develop
a multitude of Phase I-III trials, establish a tissue bank, and meet on
a regular basis. Serum, lymphocytes, tissue all need to be banked with
the patients permission prospectively. Its a huge effort and logistical
It is encouraging that this issue has stirred so many hearts.
December 1, 1998
*** POSTED NOVEMBER 30, 1998 ***
Defense Lawyer's "No Benefit" Theory Promotes Doom and Despair,
Dr. Corey Langer, 12/23/98
I recently received your letter dated 10/30/8 regarding the potential benefit
of early detection of mesothelioma. My reply follows:
To date, no randomized studies adequately address this issue. The ideal
trail would randomize early stage mesothelioma patients to best supportive
care of palliative unimodal therapy vs combined modality surgery and chemotherapy
with or without radiation. However, the absence of trials proving benefit
does not constitute proof of the converse: that early detection and diagnosis
yields no benefit. Sugarbaker and colleagues reviewed results of multimodal
treatment in 94 consecutive patients (PROC ASCO, Volume 14, March 1995,
A-1083), and reported their findings at the American Study of Clinical
Oncology Meeting in 1995. Treatment consisted of extra-pleural pneumonectomy,
postoperative chemotherapy (CAP regimen) for at least two courses and
XRT (45 Gy). Mean age was 54. Patients had either stage I or II disease
(JCO 11: 1172-1178, 1993). Median survival was 21 months, and overall
survival at two years 48%, considerably better than instonic controls.
In addition, the five year survival rate exceeded 20%. This sort of approach
obviously needs to be compared to either surgery alone or chemotherapy
alone, but such an effort would require international cooperation.
While early pleural mesothelioma can potentially be detected early, peritoneal
mesothelioma generally defies early detection. Such patients usually present
with abdominal distention +/- ascites. Even here, aggressive surgical
debulking followed by interpertioneal therapy may lead to long term survival
benefit (CJ Langer, J of Surg Oncol., 60:100-105, 1995).
The contention that earlier detection yields absolutely "no medical
benefit" is misguided and potentially harmful. It cultivates and
spreads the prevailing ethos of therapeutic nihilism that unfortunately
imbues both the medical and legal communities.
I hope my answers prove helpful.
Corey J. Langer, M.D.