Dr. Len's Cancer Blog

Expert perspective, insight and discussion

Dr. Len's Cancer Blog

The American Cancer Society

The Search for Quality in Breast Cancer Care

by Dr. Len January 28, 2006

Quality medical care is not a new topic for this blog. 

 

I have previously written about Medicare’s demonstration project designed to test the feasibility of collecting data from oncologists regarding their willingness to follow established practice guidelines as part of their routine patient care.

 

I have just spent the past two days involved in a (relatively) small group discussion about how we could improve our abilities to measure the quality of care received by women with breast cancer.  It was an interesting and productive session, including presentations and participation by some of the leading experts in quality improvement in medicine and other professions.

 

This is not a new interest for me.  Back in the early 1990’s I was a member of a guideline panel that looked at how we could improve the quality of mammograms.

 

The American College of Radiology had developed recommendations for quality mammography, and there was growing national concern that we were not doing our best to assure women that the mammogram they received met minimal quality standards.

 

To address the issue, the government decided that standards were necessary.  A panel was brought together to review the evidence as to what constituted “quality mammography.”  Following that exercise, the Congress passed the Mammography Quality Standards Act, which remains in force to the present time and is considered part of the “routine course of business” by radiologists and others interested in this question.

 

That process is not necessarily the best it could be, but it was a start in a nascent field of trying to get everyone on the same page as to what constituted quality care when performing a mammogram.

 

In the interval, we have come a long way.  The quality of our mammography machines has improved, more women are getting mammograms, and more tumors are found before they can be felt by the woman or her doctor.

 

Some other things have transpired from then until now. 

 

For example, there is now rapidly growing interest in determining how we can measure the quality of care we provide our citizens.   We have increasing computer sophistication and capability and more medical practices are implementing electronic medical records.

 

So, one would think, we are moving to make obsolete the comment of one of our congressmen, Fortney Stark, who many years ago made the observation to the effect that we know more about the shortstop of the Oakland A’s than we do about our doctors.

 

Obsolete?  The unfortunate answer is: far from it.

 

My perspective on this dates back to prior to the days I participated in the guidelines panel I mentioned above.  

 

My dream seemed sort of obvious to me: If I was looking at a process of care, I would want to have basic information about the care provided a woman from the time before she gets a mammogram, through her diagnosis and treatment to when/if the cancer came back, and, unfortunately for too many women, when she died.  Using that information, I would want to analyze the process of care to see how it could be improved.

 

I would want to know if her primary care doctor routinely referred his/her female patients age 40 and over for a screening mammogram.  I would want to know whether the doctor who reads the mammogram is competent, and how many mammograms he/she reads every year.  I would want to know how many women are referred for biopsy for suspicious lesions on the mammogram, and how many of those turn out to be positive.  I would want to know if the doctor missed a cancer on a mammogram, and understand why the doctor missed it.

 

 I would want to know if the woman with breast cancer was offered the appropriate options for treatment, and how many breast operations her surgeon performed every year.  I would want to know whether the surgeon performs more mastectomies than lumpectomies, which might indicate he/she is not offering their patients the appropriate options.  I would also want to know whether the woman got the appropriate treatment after her surgery, and ultimately I would want to know how long she lived after her surgery and what her cause of death was.

 

I would want to be able to monitor every aspect of care from beginning to end, and then I would want to analyze that information to see what I could do better.  Most importantly, I would want to have a feedback loop that gives the woman appropriate information about her care, and let her doctors know where they stand relative to others in their field of expertise, and how they could improve their care. 

 

I would want to know the woman received the appropriate care for her condition, which in turn would give her the best chances of a cancer-free long term survival.

 

It is good to want, but unfortunately we are no where near making my dream a reality.

 

How could that be?

 

It fundamentally starts with the way our health care “system” is structured.  If you go to a major center for your care, there is a reasonably good chance your doctors have looked at what they do, how they do it, and what they need to do to do it better.

 

But most of our care is not delivered in large hospitals in major metropolitan cities.  Most of it is delivered in a system made up of individual practitioners in individual offices who refer to each other, and often don’t get together to take a hard look at the same questions.  There is really no incentive to do so.  So, the opportunity to get a comprehensive view of what is going on in the care of many of our patients is lost.

 

Then there is the hard reality that many doctors don’t have electronic systems in their offices.  Primary care physicians have a hard time getting the funds to pay for the systems, and many are reluctant to invest their “intellectual capital” to set up a system, for whatever reason.  As hard as it is to believe, as was noted at our meeting this week, the systems themselves are not even designed to capture and report the information, even if we had someone who was willing and able to receive it and analyze it.

 

And then there is the willingness and commitment to make this work.  Let’s call it “buy in”, but it is much more than that.  It is a fundamental belief that this type of information gathering and analysis is necessary, that we need to make commitments as a profession to demonstrating the quality of our care, and that we are able to engage in new types of partnership and trust that heretofore just haven’t existed.  In other words, a huge leap of faith and commitment.

 

Although many of my colleagues are fully aware of the need to participate in this process, there are also many who think any effort of this type is an intrusion into the sphere of their professional judgment. 

 

Doctors, after all, aren’t selected because they like to work in systems of care.  They are selected and trained because they are independent thinkers able and willing to make decisions about serious medical problems in the middle of the night while no one else is around.   A surgeon doing a major operation doesn’t seek the opinion of a committee in order to make a decision to tie off a bleeding vessel or resect a cancer when in the operating room faced with an open abdomen.

 

If you asked a room full of doctors which one(s) provided less than standard care, how many hands do you think would be raised?  One prominent medical leader recently opined in an editorial that every doctor is a quality physician, and that essentially all of these quality improvement activities were not necessary.  (This opinion piece had an immediate response from leaders in medicine and the quality health care movement.  Please see link.)

 

The evidence shows otherwise.  But that’s not really the point of this blog today.

 

The point is that we need to make it a national priority to get everyone on the same page.  We need a national commitment to say that we need this information, we need to analyze the information, and we need to work to improve our care without fear of retribution.  In other words, we need to develop a culture of improvement in health care.

 

When I think about these issues, I think of the over 260,000 women who will be diagnosed with breast cancer this year.  I think about the need for every eligible woman who needs a mammogram to be able to get one.  If she has cancer, I want her to get the right care.  It doesn’t have to come from the world’s leading expert.  But it should come from someone who is committed to applying the best skill and knowledge about the treatment that is available to us today.  And I know that unless we measure it, we have no assurance that it is happening—the doctors’ assurances notwithstanding.

 

So back to my meeting and the commitments of my colleagues, patients and others who participated.   The task to accomplish the goal is overwhelming, but as we all agreed we must start somewhere.

 

The betting is that the goal will not be achieved in my lifetime.  Too many barriers that are organizational, political, financial, legislative and regulatory for any expectation that I will see this influence the care I receive.

 

But it might—just might—influence the care of my wife and my children and their children.  To do our best, we must do the right thing, and that is for us to commit to this process and do everything in our power to make it happen.

 

++++++++

 

My hat is off to Laura Esserman, MD from the University of California San Francisco who is the force behind the meeting I described above.  Her fortitude, will and commitment may be just what is needed to give people the push to move forward on the vision that many of us share.  I was honored to be asked to participate.

 

 

Filed Under:

Using the Media: You Need to Get It Right

by Dr. Len January 25, 2006

What started out yesterday as a routine request from a journalist to comment on a routine press release about a scientific report became one of the more interesting examples of why what you read may not always be what you think it is.

 

Several months ago, I discussed the information process and how it influences the behaviors of patients and physicians in cancer treatment.  An important element of that discussion is the need for everyone to be responsible in the process.  In fact, not just responsible, but exceptionally responsible, since the reports of cancer research outcomes may affect someone’s life very directly.

 

It is not just the doctors and the patients who are interested in what the media has to say about cancer treatments and breakthroughs.  So are the financial folks, who look for clues that a company has developed something important that may influence the performance of that company, and eventually impact their profits and their stock prices.

 

How a story is presented can influence those very important perceptions.  Presentations don’t have to be wrong to be misleading.

 

The “process” used to work differently years ago.  Companies or research institutes would develop a drug that would be a candidate for a new cancer treatment.  The compound would be put through a series of laboratory experiments, and if those were successful the drug would find its way into clinical trials in cancer patients.

 

These trials would be conducted generally in three “phases”: phase I was the initial use in patients, generally people who had failed other potentially useful drugs, and who had no other options.  The drugs would be administered in increasing doses, with an eye primarily on the toxicity of the drug, and to some degree which cancers (if any) responded to the new drug.

 

The process was very deliberative, and detailed observations were made.

 

After the phase I trial was completed, the investigators would move on to phase II, where they would try the drug in cancers that either theoretically might respond to the new drug, or in those cancers were some response may have been seen in phase II.

 

If responses were noted in a specific cancer, the drug would then move on to phase III, usually with a pretty good understanding of what the tolerable and effective doses would be, and with an eye towards treating larger numbers of patients with specific cancers where the drug had shown some benefit in phase II.

 

At each of these junctures, if the trials were successful, the investigators would prepare reports to be presented at meetings of their peers, and submit their articles describing their work to medical journals.  These journals would have the reports and the data carefully scrutinized by peers of the researchers to be certain the data was complete and fairly presented.  If the research paper passed muster, it would be published for all to see.

 

This wasn’t a perfect system, but it wasn’t bad either.   It relied on trust in reporting the data, and the investigators usually didn’t have much direct personal benefit in the outcome of the study, other than the accolades and glory that would come from doing good work that may have had significant impact.

 

A couple of years ago, when I was working as a medical editor, I began to take note of a trend that was somewhat disconcerting to me.  Once again I need to stress that there was no wrongdoing or implied wrongdoing, but I found it interesting nonetheless.  My observation was that a number of the reports of Phase I and Phase II trials were coming directly from the drug companies in the form of a press release.  This would happen, not infrequently, before any data had been presented publicly in either a presentation or a journal article.

 

On several occasions, since the press release had received notice, I would have to prepare a report for our web news stories.  I would call the phone number on the press release, ask for the data, and was told that it was not available.  Or an abstract had been presented and I couldn’t get access to the slides from the meeting.

 

The result was that, not infrequently, I didn’t write the story or if I did I was not comfortable that I had all of the information I needed to judge for myself how significant the findings really were (I won’t get into detail here how numbers can be made to look good, but you better believe they can be presented in a number of ways that makes a benefit look larger than it is.  For those of you out there who are statistic mavens, think in terms of absolute and relative risk.).

 

That is what brings me to yesterday’s story.

 

As I mentioned, it started out as a routine request from a competent reporter who I have talked with previously.  A company had issued a press release announcing outstanding results in the treatment of an aggressive, non-curable form of lymphoma.  They implied that the results were related to the use of a patient specific vaccine the company manufactured.  The company’s stock, though thinly traded, went up after a number of the financial news services spread the word.

 

Vaccines are a hot topic these days, and I have commented on recent reports regarding melanoma and pancreatic cancer vaccines in late 2005.  One of these reports was from the company, and another was reported in a presentation at a meeting.  Both were promising. 

 

There were other recent research reports about the immune response to vaccines.  One in particular described how a kidney cancer vaccine produced an immune response that most of us believe is important to getting good results in cancer treatment.  But, and this is a very important but, those researchers did not say in their reports that this implied a breakthrough in treating patients with kidney cancer.  That would be the subject of continuing clinical research.

 

So here we have a headline that implied new research results (performed, I might add, by very reputable researchers from very reputable cancer centers and reported in a very reputable medical journal) showed amazing responses in a disease called mantle cell lymphoma, which is notoriously difficult to treat and cannot be cured.

 

As I mentioned, the company had issued a press release on the topic.  Again, nothing wrong with that.  They quoted the number of people who had a response to the “new” treatment with chemotherapy and vaccine.  Nothing amiss there either.  If the headlines were right, this was a significant piece of research and the information was important.

 

But, being the somewhat stubborn person that I am, I asked for a copy of the article reporting these results.

 

Shortly thereafter, with the able help of my colleagues at the Society, I had an email copy of the journal article on my computer. 

 

But, I thought, there must be some mistake.  This was an article from September 2005, not January 24th.  And, it did not have any mention in the title that this was about a new treatment for patients with mantle cell lymphoma.  No, this was an article describing in elegant detail how the researchers measured the immune response of cancer patients in a unique situation where there immune cells had been destroyed by another generally accepted cancer treatment called Rituxan, and how the patients developed (or didn’t develop, as the case was for several of them) an immune response to another vaccine that was administered at a time when their immune system was severely compromised.

 

That’s not to say the article didn’t say how many patients were treated with the chemotherapy/Rituxan/vaccine combination, nor is it to say that the article didn’t mention in passing how many of the patients responded to the chemotherapy (the vaccine in question was administered, in most cases, several months after the patients had completed the initial two phases of treatment).  And, in another part of the paper, the authors indicated that most of the patients had relapsed.

 

No, this was not a paper being presented to show the results of a new cancer treatment.  This was a paper about the immune system, and whether or not it had to be completely intact to develop antibodies to the vaccine.  End of story.

 

Now my interest was piqued even further.  As is usually the situation, these stories land on my desk in the middle of my other daily activities.  So I must emphasize that I did not have a lot of time to do a lot of research.  But, based on the references in the journal article, and some other search techniques that I commonly use, I did a quick evaluation of what had been published on mantle cell lymphoma treatment with a specific eye towards seeing whether anyone has reported recently success with this particular form of treatment.

 

The answer? I couldn’t find anything suggesting that this particular vaccine had made any significant contribution to the treatment of mantle cell lymphoma.  Review articles in reputable cancer treatment journals didn’t mention the vaccine.  An article published in 2004 in a cancer journal written by one of the investigators who participated in the original research on the vaccine reported in 1999 said that the vaccine merits consideration “as another important option for investigation in MCL (mantle cell lymphoma)”, and references a phase II trial report in the same journal—from 2002 (I couldn’t access that report since we do not have a subscription to that journal, and the journal did not make the paper available on line when I tried to access it).

 

According to the National Cancer Institute, mantle cell lymphoma is considered an aggressive lymphoma that is not curable with chemotherapy.  They report that the median survival of patients with this lymphoma is 3-5 years (median means that half the patients live less than 3-5 years, and half live more).  Articles on MCL in a reputable cancer journal say that the median overall survival for patients with this cancer is approximately 3-4 years.  Another editorial said that the median “progression free survival” was 20 months.

 

So, I went back to the more recent article that led to the press release.  What information that was available in the article said that with the chemotherapy, 92% of the folks treated with the chemotherapy had a complete remission, and 8% had a partial response.  Those are indeed striking numbers.  But, looking further at the data, all of those responses had occurred before the vaccine was given.  In fact, in an article published in 2002, the researchers reported that this particular form of chemotherapy did indeed have an excellent response in a variety of lymphoma patients.  And, based on the actual observation of the patients, their median overall survival was probably going to be 89% at 49 months, which means it was projected and not actual.

 

There was more information. Patients for the most part didn’t get the vaccine until at least 3 months after the completion of their chemotherapy—and the administration of chemotherapy occurred over several months after the patients were diagnosed. 

 

Then there was the information in the article about how long these patients remained in complete remission.  That is the measure of real success in treating aggressive lymphomas, where the idea is to achieve a complete remission that may result in a cure.  That number tells a different story, since most of the patients had relapsed.  The median progression free survival was 22 months.  But that is not much different than has been reported in other recent studies.

 

The bottom line of this is that these patients responded well to chemotherapy.  They also may live longer than has been the situation in other studies.  But that does not seem to be because their initial treatment was remarkably successful.  In fact, it may mean that subsequent treatments have had excellent results.  The report itself made no claims that this was a breakthrough treatment.

 

What does all of this mean?  First, in my opinion, one must always be very cautious when reading media reports touting a new breakthrough, especially when the information is based on a press release from the company. 

 

Second, it is incumbent on the press to read these press releases critically if they are doing something more than just passing on a press release (and they indicate that in fact is what they are doing).

 

But my real concern is the message this may send to patients and families and others who are coping with a serious life-threatening disease.  There must always be foremost in our minds the impacts that press releases and media reports are going to have on patients facing a life threatening illness.  We should be held to a high standard in our research, our reports, and our representations.

 

I have not been able to find the type of report in the literature or referenced in the article that would lead me to change my recommendations for the treatment of a patient with mantle cell lymphoma, supporting a breakthrough as a result of the vaccine.  In fact, the major breakthrough in this situation appears to be the chemotherapy itself.  But despite that success, it hasn’t yet resulted in cures or a significant advance in the treatment of these patients according to the experts in the field.

 

This won’t be the first time someone presented information in the most favorable light.  And, technically, there was nothing wrong in what was done here. 

 

But, again in my personal opinion, we really owe our patients a higher standard than to suggest an article describes a breakthrough therapy, when it is clearly not the intent of the article nor justified by the results over time.

 

And, as always, if there is information that is available to refute my conclusions or clarify the information I have presented and discussed here, please, please let me know.  I would welcome being shown that I erred in my conclusions.

 

But, if I’m on target, please be careful in the future and understand the responsibility to not only get it correct, but to get it right.

 

Filed Under:

New Hope for Patients with Bladder Cancer

by Dr. Len January 18, 2006

Bladder cancer is one of those types of cancer that seems to fly under the radar screen of most folks.

 

It’s not that the disease is that uncommon.  There were estimated to be 63,000 new cases of bladder cancer in the United States this past year, and 13, 180 deaths.  The disease is more common in men than women in a ratio of about 3 to 1.  In terms of deaths in the United States, it is the 9th most common cause of death from cancer in men while for women it is much further down the list.

 

Maybe the reason we are somewhat complacent about the bladder cancer is that for many people it is not a life threatening disease.  It is frequently superficial, and requires repeated follow-up over a lifetime to look for recurrences which then require treatment. 

 

It is a cancer that is associated with smoking, and over the past several years there has been an actual decrease in its incidence, perhaps related to decreased tobacco consumption.  The decrease is most notable in African Americans.  It is also a disease of the elderly, with increasing rates of incidence as one gets older.  10 year survival rates are close to 80%, although they are much lower (a bit less than 60%) for African Americans.

 

The problem for the typical patient with this cancer is the follow-up, which means cystoscopy (looking into the bladder with a long, thin lighted tube) with or without cytology (looking at cells obtained from a urine sample under the microscope to find evidence of cancer cells) every three months in the beginning, with increasing intervals over time. 

 

There is no end point for this vigilant follow-up after the diagnosis has been made, and the initial treatment provided.  Cystoscopy can be done in the doctor’s office, but it is not a pleasant experience (Not that it is bad as it used to be: today we have flexible, lighted tubes for the procedure. Years ago the tubes were rigid metal and very uncomfortable).  Cytology, an examination for cancer cells under the microscope, is not as sensitive in disease detection for bladder cancer as it is in other situations such as the Pap test we all know about.

 

A recent report in the Journal of the American Medical Association (see note below regarding problems with the link) now suggests that another test, which has actually been around for a couple of years but has not found a place in the routine screening for bladder cancer, may help detect recurrent bladder cancer earlier, when the treatment options may be greater and the outcomes much improved.

 

The test, called BladderChek, measures a protein that is found in the urine of patients with bladder cancer.  The protein, called NMP22, is a byproduct of cancer cell division and death.  Up until now, it had been approved for use as a screening test for bladder cancer, especially in people at high risk.  The advantage of the test is that it can be done in the doctor’s office off of a voided urine sample which is easy to obtain.

 

The problem with using this test in screening for bladder cancer is that there is no evidence that large scale screening programs for bladder cancer are effective or appropriate when used in the typical person. 

 

Given the situation described above, where most of the cancers detected are either curable or very treatable over the long term, the value of a screening test for the average individual isn’t as clear as it is for diseases that can frequently lead to death such as colorectal cancer or breast cancer.

 

But when looking for recurrent disease, the situation is a different one.  Now, there is a person at high risk for having a problem.  The chance of a recurrence for even the patients with the earliest stage of bladder cancer is 50%, according to the authors in the JAMA article.  They also comment that 10-20% of the patients followed up for bladder cancer will have a recurrent cancer found at their cystoscopy.   That’s a pretty substantial number.

 

What the doctors did in this current study is combine the follow-up cystoscopy with the BladderChek test and a cytology exam.  What they found was that the urine protein test significantly improved the chances the doctor would find the recurrent cancer if it was present, when compared to cytology.  In fact, it increased the chances of finding the recurrence to about 99%.  And, that information was available immediately in the doctors’ offices, as opposed to having to wait for a lab to send back a test result from the cytology examination.

 

It is important to note that the NMP22 test itself didn’t detect every cancer that was present.  In fact, it was positive about 50% of the time the cancer had recurred.  On the other hand, the cytology examination (examination of cells under a microscope by a pathologist or trained technician) was positive only 12% of the time.

 

It was the combination of the cystoscopy and the NMP22 test that resulted in the 99% figure noted above.

 

One of the important cautions in this study is that it was a “one time only” event for the patient.  That is, the patients were only tested one time with the NMP22 test.  It was not done on repeated visits over time.  There were some instances in this study where the NMP22 test was positive, and the doctor did not see a cancer through the cystoscope.

 

That raises an intriguing question: what would happen if the test was done repeatedly over time, even with cystoscopy?  Would the test pick up the recurrence before it could be seen?  I suspect someone, somewhere is working to answer that question right now as I write this.

 

And, if we were able to pick up a recurrent cancer before it could be seen, would that mean that some of the more aggressive cancers could be treated more effectively, with a greater rate of long term survival?  We know that the longer a recurrence of bladder cancer is present, the more difficult the situation for the patient.  So, earlier detection of a recurrent bladder cancer translates into better treatment.

 

It’s too early to say what the impact of this paper is going to be on the treatment and follow-up of people with bladder cancer.  But it does improve the odds that your doctor will be able to spot a recurrence earlier, and maybe improve the treatment options for you, as well as improve the quality of your life and the length of your years.

 

I suspect we are going to be hearing more about this test, and how doctors are going to use it in their everyday practices.  But unlike the dogs that were able to smell bladder cancer in urine samples (discussed here last week), my hunch is that the benefit with this bladder test is going to be more accurate and more immediate.

 

++++++++++++++++

 

Note: The link to the abstract of the JAMA article was not working, so I have provided the link to the JAMA homepage, where the article is listed on the table of contents.

 

For disclosure purposes, we (at the American Cancer Society) have had some contacts and discussions with representatives of Matritech over the past year regarding this test.  This is not an uncommon situation for us, and many companies want us to know what they are doing.  We have received no grants or other funds from Matritech, and had no prior knowledge of this study or its results until it was published.  The topic of this blog was suggested by one of our staff who had no knowledge of those discussions.

 

 

Filed Under:

Prostate Cancer Screening: The Confusion Continues

by Dr. Len January 12, 2006

If you are a man, age 50 and over, and find all of the information you are hearing about prostate cancer just plain confusing, do not feel alone.  Because you are not the one with the problem.  In no small part, the experts you rely on to provide you with clear, concise medical information and direction have not been in your corner for some time.

 

That’s not necessarily the experts’ or the doctors’ fault.  There is so much confusing research and commentary about prostate cancer screening that someday someone will write a historical book on the subject.  It may not be a best seller, but it will reinforce the fact that you have not taken leave of your senses when it comes time to make a decision about whether or not to get screened for prostate cancer.

 

An article this week in the Archives of Internal Medicine didn’t do much to clear the clutter.  It certainly made the headlines, and the message delivered by our media friends was that prostate cancer screening is not effective.

 

Basically, the authors looked at medical records of men treated in VA Hospitals who had been diagnosed with prostate cancer between 1991 and 1995.  Then, they picked other men at random who had not been diagnosed with the disease to compare to the men with cancer.  They found 501 patients with prostate cancer, and had records reviewed from another 501 men without prostate cancer, who are what we call “matched controls.” 

 

Then, the authors looked to find the number of men in each group who had been screened for prostate cancer with the well-known PSA test.

 

As you can imagine from the press coverage, the study did not show a benefit for screening.  Essentially whether or not a man was screened for prostate cancer made no difference in the rate of death.

 

The study itself was well done, and the methods are complex and difficult to understand for both laypeople and professionals alike.  But, I’m not certain that it answers the question about whether or not prostate cancer screening works at saving lives.

 

A little historical perspective about the state of the art of PSA testing around the time the researchers analyzed may be in order.

 

I was a primary care physician in the late 1980s and early 1990s.  I recall that PSA was new at that time, and we really didn’t know much about it.  We certainly didn’t understand the nuances of the test, and we didn’t understand that any upward change in the test was an indicator for follow-up, even if it was below the “normal” threshold.  Our ultrasounds and biopsies weren’t as well perfected as they are now, and frequently we referred a patient with a slightly elevated PSA and no biopsy was done.  Instead, we were told to get the PSA again in several weeks or several months.  The tests themselves weren’t perfect, and using a different lab kit could result in a different number.

 

I could go on, but I think you can get the idea:  we know more now than we did then, and “then” was the time frame when this study was done. 

 

The bottom line is that there are too many variables in practice and understanding which existed at that time for me to have much confidence in the results of this study today, no matter the quality of the work that was done by the researchers.

 

So the arguments and the debates will go on.  The sad part is that there is also confusion among the major organizations that make recommendations to men about whether or not they should be screened. 

 

As noted in the article and the editorial which appeared in the same issue of the journal, one respected medical organization says the evidence is not sufficient to recommend routine screening for prostate cancer.  Another says that it should be “offered” to men, but that organization (which is mine, by the way) says that offering doesn’t mean endorsement of the test, and that it is important men be educated about the benefits and risks of the test so they can make an informed decision.   Yet another organization recommends the test for men at average risk age 50 and older.

 

It is this lack of clarity that is really a problem for everyone who is trying to decide what to do.

 

In addition, the rate of death from prostate cancer has been declining.  But although some advocates say this is due to increased screening for prostate cancer, others say it is due to better treatment.  What isn’t widely promoted as a point of view is that the rates of prostate cancer are also decreasing in other developed countries that do not have a widespread screening availability.  And, according to the editorial, even here in the United States, the decreased death rates from prostate cancer when looked at region by region don’t correlate with the intensity of screening.  That is, in plainer words, the more men that are screened doesn’t necessarily relate to a lower rate of death from prostate cancer.

 

This is no idle discussion.  There are potential benefits from prostate cancer screening, but there are also significant drawbacks.

 

The PSA test, for example, is more frequently abnormal because of prostate enlargement than from cancer.  That means a lot of men have biopsies and develop fear of cancer, when in fact the only problem they have is typical age related benign prostate enlargement.

 

Also, the treatment for prostate cancer may not be exactly a walk in the park, with serious side effects from surgery and also from radiation therapy, both accepted treatments for this disease.  And, many men with prostate cancer are treated when we know that the disease (which becomes almost universal as men age and live long enough) would never cause them a problem during their lifetimes.

 

As noted in the editorial, there are some studies underway in the United States and Europe which hopefully will answer the dilemma of prostate cancer screening with some degree of definitiveness.   Those results are supposed to be available in 2009.  The studies have been underway for so long that I can’t even remember when they started.  I have been hearing about these again and again for years, so it’s nice to know the end is in sight.

 

Ultimately, what we need is a test that can indeed find prostate cancer early, and then another test that can distinguish whether or not a particular prostate cancer is one that needs to be treated, or even treated aggressively.

 

In the meantime, you are going to be left with confusion and lack of clarity.  You can gather information, and you should be informed about the benefits and risks.  You will make a decision whether or not you want to be tested.  But what you won’t know is whether or not the decision to get the PSA test will really in truth save your life.

 

To that question, unfortunately, right now we just don’t have the answer. 

Filed Under:

Dogs And The Early Detection of Cancer

by Dr. Len January 11, 2006

The first time I heard about dogs being able to “sniff” cancer in a sample of urine was many months ago.  I have to admit that at the time I was very, very skeptical.

 

The research concept that was reported in an article in the BMJ (also known to many of us as the British Medical Journal) in September of 2004 was fairly straightforward: dogs have a very well developed sense of smell, and maybe they can smell something in a body fluid that may be able to detect whether or not the patient had cancer. 

 

As the researchers reported, up to that time there had been several anecdotal reports of pet dogs alerting their owners to the fact that something was amiss, and that something turned out to be cancer.

 

What the researchers found was that in a group six ordinary dogs they were able to train the dogs to detect something through their sense of smell in the urine of cancer patients that was different from the urine of people without bladder cancer. 

 

The test wasn’t perfect.   The dogs were right 41% of the time, compared to 14% which would have been the expectation if the dogs were just guessing.  Despite that caution, the story received a lot of media attention for the obvious reasons: it was offbeat, and it suggested a possible simple solution to a complex problem.  Even 60 Minutes weighed in.

 

I didn’t hear anything more about this concept until this week, when a paper published in a journal called Integrative Cancer Therapies and made available online generated a considerable amount of media interest, probably for the same reasons noted above.

 

In this more recent article, the researchers reported that they were able to train several local dogs to determine which breath samples came from patients with lung or breast cancer.  Not only could the dogs pick out the right sample almost all of the time, but they could also detect samples from folks with even early stage disease.

 

Before everyone goes out and starts creating cancer screening programs based on the unique ability of dogs to differentiate body fluid or breath samples from cancer patients compared to people without cancer, there a couple of points that have to be made.

 

First, let’s talk about what may be going on here.

 

Our bodies in fact are, among other things, pretty neat protein and chemical factories when you stop and think about it.  We are made up of cells that create proteins, and create waste products and other compounds that are part of our daily existence.

 

For many years, there has been considerable interest in identifying chemicals, proteins and other markers in our body chemistry that may give a clue to the presence of cancer.  The goal, ultimately, is to be able to measure something through a lab test that is produced specifically by a cancer, and that would allow us to become aware a cancer is present before it can be felt by examination, or found by an x-ray or other imaging test.  Then, maybe the cancer could be treated before it ever becomes a problem.

 

Research into these types of detection possibilities has accelerated over the past several years, as our knowledge of cancer and the quality of our research tools have improved rapidly.  A recent editorial in the Journal of Clinical Oncology nicely summarizes these efforts and some of the problems that researchers have faced, including some of the false starts that resulted in considerable excitement but did not pan out.

 

As part of our “body factory,” there are going to be products produced that are “volatile” in nature.  That means they are excreted through the body in a gaseous form and may be associated with certain odors.

 

For example, when a person has poorly controlled diabetes, they produce a substance called ketones which can be measured in their blood and urine.  However, the body also excretes this material through the lungs, much like it gets rid of carbon dioxide while it takes in oxygen.  Those ketones smell, and that is what gives the characteristic odor associated with diabetic coma.  We doctors usually are able to smell the ketones when they get to a high enough level in a patient’s breath.

 

Similarly, as a physician, you can also smell alcohol on the breath of a chronic abuser.  That is, in fact, one of the ways the body gets rid of the breakdown products of alcohol consumption.  Most of us are very familiar with the breath test that police use to determine the alcohol level in a person’s body.

 

There are many other examples, but I suspect you get the idea: the body creates chemicals that may be produced in small amounts, but in fact in larger concentrations may create a smell that is characteristic of the process.  We humans can smell these things when they are present in large amounts, but we can’t smell these chemicals when the concentration in the air is very small.  Dogs, with a very highly developed sense of smell, may be able to detect these odors.

 

If we could prove the association between cancer and the production of some of these chemical products in small amounts that could be smelled by a dog, we could then concentrate on trying to find that compound.  If we could do that, then the compound could be measured.  We would, in essence, use the skills of the dogs to guide us to find the compound.    

 

It is possible that the dog could be better than our fancy machines.  We would be able to short circuit the process of sifting through thousands and thousands of possible candidates to zero in on the one that counts.  The compound, whatever it is, may be in the body in amounts too small to actually isolate it without getting a clue from our canine friends.

 

That is really where, in my opinion, the action is for this particular approach.

I do not envision long lines of lab specimens lined up, with a trained pooch walking down the aisle and sitting down in front of a urine sample or a breath sample when the dog smells the smell. 

 

The experiments themselves and how they were constructed do not point in that direction (pardon the pun regarding pointing).  What the researchers did was demonstrate that the dogs were able to pick the cancer sample out from four normal specimens in one test, and from six samples in the other test.  The dogs did not have to go down a row of 100 samples, and pick out all the cancer samples from all the normal samples, nor did they go through thousands of samples of healthy patients and find those who had a lung, breast or bladder cancer.

 

So what have we ended up with after all of this excitement?

 

We know that your neighborhood pooch can be trained to pick out a cancer sample from samples which came from a group of folks not known to have cancer.  We don’t know what it is they smell, and we don’t know how much of whatever compound they smell is present in the body.

 

We don’t know if this is a real breakthrough. We do know that it has not been demonstrated yet—based on these studies—that this is going to have significant impact on the early detection of cancer.

 

But you are hearing from someone who was a skeptic that there may be something here.  Stranger things have happened in science, and in the treatment of cancer.  Far be it from me to be an absolute doubter about this possibility. 

 

Skeptical?  Yes, but that’s my nature about a lot of new discoveries and claims.  An absolute skeptic?  No longer.  My mind is open, and I look forward to continued research reports with interest.

 

Filed Under:

Does Vitamin D Really Reduce The Risk Of Cancer?

by Dr. Len January 06, 2006

The vitamin D issue has arisen once again.

 

Back in April, at a major national scientific conference, a Harvard researcher gave a talk on the role of vitamin D in the prevention of cancer.  The lecture, which is available online, was well done and based on scientific data.  (See presentation by Dr. Edward Giovanucci on this webpage.) It didn’t get much notice, however, until an Associated Press reporter did a story on it a couple of weeks later.

 

That’s when the proverbial “stuff” hit the fan.  Media outlets around the world jumped on the story immediately and fanned the flames that vitamin D was the answer to decreasing the incidence of several forms of cancer that afflict hundreds of thousands of people every year in the United States.

 

Other scientists were a bit more reserved in their thinking, but still were of the opinion that this is an area that needs further examination and consideration.

 

One of the major concerns of many, including me, was that the public would read only one half of the story, namely that sun exposure (the major source for the production of Vitamin D in the body) was good for you, and that it was now considered a good thing to go out in the sun, get a tan, but just not get a sunburn.

 

For example, I was interviewed on the Fox News Channel, and while I was talking in a studio in Washington, the channel apparently was showing pictures of people sunbathing on the beach.  That was a hard visual to overcome with scientific words that most people probably weren’t paying much attention to.

 

The reason so many folks in the medical community were concerned was that we have spent a good deal of time (and money) trying to educate people about the dangers of sun exposure.  We have an increasing frequency of skin cancers, including melanomas which are the most dangerous form of skin cancer.  There are also other skin related problems, such as premature or extensive aging of the skin, that result from sun exposure.

 

And we can’t forget the young people, especially young women, who mistakenly believe that a good tan is a sign of good health.  The vitamin D story had the risk of giving them the ammunition they needed to overcome whatever reservations their parents may have had about sun exposure and tanning booths.

 

Since this story “broke” in the early summer, there was the real possibility that a lot of good work could be undone by people who didn’t understand the entire issue.  And that in no small part is because scientific organizations, including the American Cancer Society, did not feel the science was in place (including detailed, careful discussion of the data) to change our current recommendations and provide guidance that going out in the sun was in fact a good thing for you (see our web page for further information).

 

How did we get into this predicament in the first place?

 

It has been clear to many researchers for some time that there is a distribution in the incidence of cancers in this country based on where people live.  There are maps which very nicely demonstrate that where you live may influence your risk of developing certain cancers.

 

That observation led some to conclude that sun exposure may be a factor in cancer incidence given that more sun at certain latitudes was associated with a lower incidence of these cancers.

 

This has led some researchers to conclude, based on certain studies, that the reason this effect occurs was due to an increase in vitamin D levels, which occurs with greater exposure to the sun.  That in turn led to the report in April, and the following media frenzy.

 

What did not get answered by the maps was whether other factors could also play a role, whether that be dietary habits or physical exercise or some other unknown factor.

 

Research has shown us time and again is that it frequently is not so obvious why we see certain patterns of disease.  It takes a lot of research effort and careful examination of the data to understand biological phenomenon, such as the development of cancer.

 

In the interval since the events of this past summer, many organizations (including the American Cancer Society) have begun to look more closely at the question, and try to get some consensus on what recommendations we can make to the public. 

 

Critical to this effort is confirming the science, and making recommendations that take into account the benefits and risks of sun exposure, as well as how to guide people who live in different parts of the country which may have more or fewer sunny days, for example.  And we can’t forget that many of us have different types of skin pigmentation.  Some are very sensitive to the sun, some less so.  Some of us are African American, and sun exposure would not be sufficient to get adequate levels of vitamin D which means we would have to take dietary supplements (more about that later in this discussion) if we are to get the benefit of adequate levels of vitamin D, if the theory proves to be correct.

 

While I was on vacation these past couple of weeks, two new papers were published in scientific journals once again discussing vitamin D research and promoting the vitamin as a means to reduce cancer incidence.  Both the papers shared many of the same authors.

 

In The Journal of Steroid Biochemistry and Molecular Biology, the researchers looked at the question of whether there is a “dose-response” relationship between either vitamin D levels in the body or the intake of vitamin D on the incidence of colorectal cancer.  They concluded from their research that either an intake of oral vitamin D of 1000 IU/day or a high level of vitamin D in the blood reduced the incidence of colorectal cancer by 50%.

 

One of the interesting observations in this paper was the fact that 95% of our vitamin D actually comes from sun exposure.   As a result, many of us are vitamin D deficient, since we spend much of our time indoors.  Also, if you live in Boston, the authors note that there are 2007 hours/year of sunlight, compared to 1400 hours/year in Boston.  Finally, a dose of 1000IU of vitamin D, according to the authors, is safe.  They comment that the National Academy of Sciences has established a “maximum safe level” of vitamin D intake of 2400 IU/day, far more than many of us get and well above the1000 IU level recommended in the research paper.

 

The other paper, which appeared in the American Journal of Public Health, was more descriptive of the research that has been done on vitamin D in general in relation to cancer.  In this article, the authors mentioned that there is a high prevalence of vitamin D deficiency in the United States.  They also pointed out that some research studies (although not all) have suggested that higher levels of vitamin D can reduce the risk of developing colon, breast, prostate and ovarian cancer.

 

Prostate cancer studies are an interesting example of how this subject can be confusing.  The authors report of 24 studies of prostate cancer and vitamin D, 13 showed a positive benefit, one suggested a benefit, and 11 showed no association.  In the scientific world, this is not what we would call a “home run.”  Similar inconsistent results were found with other cancers as well.

 

The authors conclude their report by recommending that we increase our oral vitamin D intake to 800-1000 IU/day.  They also recommend a daily sun exposure of 15 minutes daily in the summer and 20 minutes in the early fall or late spring, “from 11AM to 2PM under clear skies, assuming exposure of arms, shoulders and back.  Blacks require twice as long.  During November to March, north of 37 degrees latitude in the Northeastern and mid-Atlantic regions, no amount of solar exposure is sufficient.”

 

They also caution that moderation is appropriate, and acknowledge the damage the sun can cause.  They emphasize the need to avoid a sunburn, and that intentional exposure of the face should be minimized.  They go on to say that “oral vitamin D3 supplementation, rather than solar exposure, should be used by fair-skinned or sun-sensitive persons or by individuals taking medicines causing photosensitivity.”

 

I am not providing all of this information because I agree with the authors, their recommendations, or their conclusions.  Past experience has shown there is much more to be known about whether or not vitamin D really reduces the risk of cancer.  Further research must be done, because there are also risks associated with the type of sun exposures noted above.  Not to mention that it is very, very difficult to make a “one size fits all” recommendation regarding the amount and timing of sun exposure that will achieve the desired effect.

 

In particular, I do not agree with the statement that we will have 50% fewer colon cancer deaths if everyone starts taking increased amounts of vitamin D and if doctors start routinely measuring vitamin D levels as part of the annual physical, as the authors recommend.

 

As with any cancer, colon cancer has a complex etiology.  We do know that if we screened more people at average risk age 50 and older we would reduce the incidence and deaths from colon cancer.  I’m not certain, on a personal level, that in the real world increasing vitamin D levels would have the same effect.

 

That’s not to say that this theory is necessarily incorrect.  That is not my message.  But it is one that requires scrutiny and analysis.

 

As I mentioned earlier, many of us wish that the real world was only so simple.  Yes, we have seen remarkable advances in health as a result of understanding vitamins (vitamin C and folate come to mind, among others) where bad diseases have had a remarkable reduction in incidence as a result of vitamin supplementation.  Although vitamin D may have a role in cancer prevention, we need to do the research that will demonstrate that conclusively.  Past experience shows us that vitamins which were thought to be beneficial relative to reducing cancer risk actually were harmful.

 

So there are no easy answers.  I have provided this overview so you can make your own decision.  But bear in mind the jury is still out on this one, no matter how many times the newspapers, radio and TV repeat the message.

Filed Under:

Ovarian Cancer: Something Old, Something New

by Dr. Len January 04, 2006

 

I do hope that you and yours had a very happy holiday.  I want to wish you health, happiness and success for the New Year.

 

I apologize to those who wonder where I may have been the past several weeks.  I took some much needed time off from work, with every intention of continuing to post the blog occasionally during the interval.  As situations dictated, I had to really take some time off for various reasons, so the computer remained closed for the duration.  But, we are back, and hopefully that won’t happen again—at least not until next December!

 

Now, back to the blog:

 

 

There is an article and editorial released for publication this afternoon in the New England Journal of Medicine about the use of intraperitoneal chemotherapy (giving chemotherapy drugs directly into the abdomen through a small tube, or catheter) in the treatment of advanced ovarian cancer.  They are accompanied by a press release from the National Cancer Institute, and I suspect this will get a fair amount of media coverage.

 

The article interests me for a couple of reasons:

 

First, the therapy isn’t really new.  Second, the news release suggests that this is now the standard of care, despite many of the problems with the treatment that have still not been addressed.

 

Those issues do not, however, cloud the fact that the study is significant and that the survivals are considerably better than what has been seen before in the treatment of women with this stage of disease.

 

Let’s examine for a moment why the issue is so important.

 

Ovarian cancer is not rare, but it is not common.  In 2005, the American Cancer Society estimates that 22,220 women will be diagnosed with ovarian cancer, while 16,210 women will die from the disease. In fact, over the period from 1975 through 2002 (the latest year for which statistics are available), the rate of ovarian cancer has actually been decreasing about 0.5% each year (that means for every 100,000 women, there were about 14% fewer cases of ovarian cancer in 2002 than would have been expected compared to the rate of the disease that occurred in 1975).

 

The reason ovarian cancer is of so much concern is that it is the fourth most common cause of cancer death in women (6% of cancer deaths), and strikes many of those women well before their 65th birthdays.  It is also a silent disease: symptoms leading to diagnosis are almost always associated with advanced ovarian cancer.  Unfortunately, there are no reliable screening tests that can be recommended for women who are at average risk of the disease.  The net result is that very few women are diagnosed with ovarian cancer when it remains confined to the ovary and has the greatest opportunity to be cured by surgery.

 

When ovarian cancer spreads, it usually stays within the abdomen and doesn’t spread widely like so many other cancers.  As a result, doctors for many decades have focused their treatment efforts on how to attack this cancer in the abdomen.

 

Years ago, there were some attempts at treating the whole abdomen with radiation therapy, but lack of success and significant side effects resulted in the abandonment of this approach (doctors used both what we call external beam radiation therapy and injections of radioactive isotopes into the abdomen during that era.  The result was not much success and a lot a scarring in the abdomen which in turn led to blockages of the bowel among other side effects).

 

As we developed cancer drugs which seemed to have some greater benefit in treating ovarian cancer beyond the initial oral drugs we used in the 1960s and 1970s, some experts thought that it would be better to give the drugs directly into the abdomen instead of intravenously through a needle.

 

Simultaneous with this, doctors began to aggressively remove the cancer that developed in the abdomen through an operation called “debulking.”  The goal of these surgeries was to surgically remove as much cancer as possible and leave behind the smallest amount of cancer, in the event it could not be completely resected.

 

With the new chemotherapy and the more aggressive surgeries, doctors were hopeful that we could effectively treat this cancer.  There was even a routine recommendation for many of these patients that they have second-look surgeries to check on the response of the treatment.

 

All of this occurred many years ago.  There was improvement in the treatment of women with ovarian cancer, but not as much as had been hoped for.  The idea of giving chemotherapy directly into the abdomen (called intraperitoneal chemotherapy) more or less fell by the wayside.  We never did develop chemotherapy drugs that were able to cure ovarian cancer.

 

The current study resurrects the intraperitoneal treatment, combines it with more standard intravenous chemotherapy, and compares it to a treatment that uses only chemoterhapy drugs given intravenously.

 

The researchers report that there were significant improvements in two measures of treatment success where the combined intraperitoneal/intravenous approach was compared to the standard IV treatment: the time it takes from when the therapy starts until the disease starts to progress, and overall survival from the cancer.

 

For the first measure, for the women who had the combined therapy, the median time to progression was 23.8 months from the time they started the treatment compared to the women on the standard IV drugs who took a median of 18.3 months (“median” means one half of the women progressed before the time noted, while the other half took longer).  The difference in the medians is about 5 ½ months.

 

The improvement in the second measure of the study, survival from the start of treatment, was even more dramatic.  These numbers were 65.6 and 49.7 months, respectively, for the median survival.  This difference is about 16 months.

 

That’s the good news.  The bad news is that the treatment with the medicines injected into the abdomen did not come without a significant personal cost.  The women who received the combined treatment had a much worse quality of life while they were receiving the treatment.  Fortunately, this got much better over the next year and by that time both groups had about the same quality of life.

 

This probably was due to some of the severe side effects of the combined treatment.  Those women had severe abdominal pain, fatigue, and other side effects.  Only about 4 out of the 10 women who were supposed to receive the treatment into the abdomen were able to complete their entire course.  Almost half of the women received 3 or fewer of the planned abdominal treatments.

 

Despite the fact that completion of the treatment was so difficult, the results were still significant.  What this means to me is that if we are able to find ways to deal with some of the side effects of the treatment, and help women get through the entire treatment course, the results may be even more dramatic than those reported.  (Perhaps an explanation would be helpful.  See * below if interested.)

 

So what does this mean? 

 

First, even old, discarded treatment approaches may have some value when reexamined in the light of current knowledge (see the previous blog entry on vitamin C as an example of how new thinking can revive interest in something that has been previously tried and thought not to be effective).  Second, we still have much work to do to make this treatment even more effective, such as finding better ways to overcome the significant side effects of the treatment, and improve the catheters we need to inject the drug into the abdomen.  Third, we need to overcome biases among many physicians that intraperitoneal chemotherapy doesn’t work.  This study suggests that it does, and we have to train more doctors to give the treatment.  Finally, we need to continue the clinical trials to figure out the right drugs to use in this approach to get the maximum benefit.

 

I agree with the doctor who wrote the editorial in the same edition of the Journal that we are going to have to figure out how to get this treatment to the women who need it.  We need to train the doctors to do it, and we need to figure out ways to give this in community hospitals and cancer centers. We need to have extremely supportive and knowledgeable nurses, especially since the pain and fatigue of this treatment are so substantial.  And for women who don’t have access to this treatment in their home towns, we need to find ways to get them to centers that do have the capability to treat them.

 

But, with all the interest and possible excitement that this research may generate, we must not lose sight of the fact that we need to find better tools to discover ovarian cancer at its earliest stage, when there is a much better chance for a real cure.  That would represent the best progress against this very insidious and deadly disease.

 

 

 

 

* When we report clinical trials, we usually do so on what is called an “intent to treat” basis.  That means that once assigned to a treatment group, even if you don’t complete the treatment, you are still counted as part of that group.  This hopefully gives us a better understanding of what the true impact of the treatment is, as opposed to counting only those who complete an entire course of treatment which could make the treatment look better than it really is.  In this particular study, the practical implication is that even though only about half of the women got the full course of treatment, the results for those women were so much better than the standard treatment that it made the results better for the entire “combined treatment” group—even those who didn’t complete the whole course of therapy.  I suspect that if all of the women were able to complete the treatment, there would have been even greater success for the combined treatment group.

 

Filed Under:

About Dr. Len

Dr. Len

J. Leonard Lichtenfeld, MD, MACP - Dr. Lichtenfeld is Deputy Chief Medical Officer for the national office of the American Cancer Society.

MORE »

 

Recent Comments

Comment RSS