Every year lung cancer extracts a terrible toll in this country.

Here are some of the numbers:

• Lung cancer is the leading cause of cancer death in the United States in 2006

• In 2006, 174,470 people will be diagnosed with lung cancer, and 167,050 will die from this disease

• 15 years of life are lost by the average person who dies from lung cancer

• 2,3643,900 years of life were lost in this country in 2002 from lung cancer

It is obvious that anything we can do to decrease the rate of deaths from lung cancer will have a huge impact on the health and length of life of this country.

As hard as many have tried, we still have around 20% of the adult population who smoke, and there is a continuing tobacco addiction crisis among young people in the United States.

For those who are smokers, and those who are former smokers who have quit using tobacco (who are now in the majority relative to those who have ever used tobacco), there has been little we can offer to prevent this disease.

And, up until recently, there has been no screening test that we can recommend to everyone who has been a smoker or exposed extensively to second hand smoke that might find lung cancer early and offer the benefit of saving their lives.

An article reported in today’s New England Journal of Medicine may go a long way to changing our perceptions regarding the benefits of screening for lung cancer in an effort to catch the disease early.

First, a bit of background.

About 30 years ago a series of studies were reported that indicated the best available screening with chest x-rays and sputum cytology (examining sputum samples of smokers for evidence of cancer, somewhat like a pap smear for the lungs) provided no survival benefit for smokers.

I can recall the papers—although interestingly they are not cited in the current report or an accompanying editorial—and the lectures from those years.   The study researchers went out of their way to point out that even finding early lung cancers didn’t mean that the patients survived longer.

This finding was different from what we have seen in other cancers, namely that discovering a lung cancer earlier meant meaningfully longer survival for most patients, such as is the case for breast and colorectal cancer.

The result of those studies was that many organizations—including the American Cancer Society—came out against any form of routine screening for lung cancer, which at that time was predominantly done by chest x-ray.

As time has moved on, so has technology. 

CT scans were not widely available until the mid-1970’s, and those CT scanners--although revolutionary at the time--were nowhere near as quick or technologically advanced as what we have available today.

There have also been some researchers in the medical community who have argued that the data interpretations from the original studies were flawed, and that there was in fact a benefit seen from screening in the earlier studies.

In the midst of this controversy, a group of researchers led by doctors from Cornell University in New York began a study of smokers and former smokers using more advanced CT scan technology which was able to clearly see small lesions in the lungs.

For several years they have been presenting their data, showing that they have been able to find lung cancers early, and that survival was considerably improved. 

Along the way they have refined their study protocol to improve the accuracy of their procedures, trying to winnow down the many lesions they were finding in the lungs so that they would selectively biopsy only those with a high likelihood of being cancerous.

More recently, the American Cancer Society and others supported a trial called the National Lung Screening Trial which randomly assigned participants to either chest x-ray or CT screening.   50,000 people are participating in this trial, and the results of that effort are still several years away from being analyzed and reported.

In the current report from the New York group (which in fact is now an international effort) in today’s New England Journal of Medicine, the authors report the survival results from their study. 

Those results are indeed very impressive, and strongly suggest that screening smokers, former smokers, people with occupational exposure (such as asbestos) and those who have had substantial second hand tobacco exposure is very effective in reducing deaths from lung cancer.

The researchers performed an initial CT scan lung screening for over 31,000 people without symptoms from 1993 through 2005.  They also did another 27,456 follow-up CT screens on some of the same people between 7 and 18 months after the primary screen.

If they found an abnormality on the CT scan, the doctors followed a very specific protocol to determine whether or not the nodule did in fact have a high probability of being cancer.

This is important because doctors see many things in the lungs of smokers and former smokers that may look like cancer on the CT scan but are in fact not cancerous lesions. 

That has been one of the downsides of doing this test, since there are risks associated with doing further workups on patients with suspected cancers.  Those risks can include serious medical harm and even death, since many of these people are not exactly in prime health because of their smoking history and other medical conditions.

The important outcome of this study is that of the people that were screened with CT scan, either with an initial or a follow-up scan, 484 were diagnosed with lung cancer.

Of these 484 folks, 412 or 85% had stage I, or early stage, lung cancer.

For those 412 people with early stage disease, the estimated 10 year survival rate was 88%.

302 patients had their lung cancers removed within one month of diagnosis.  For them, the estimated 10 year survival rate was 92%.

In other studies, the survival rate for Stage I lung cancer has been around 70%.  When patients present with advanced Stage IV disease, the survival is 5%.

The most recent national data indicate that 16% of lung cancer patients present with localized disease, 37% with regional disease, and 39% with distant disease (7% are not staged).

Because so many folks present with more advanced disease, the overall five year survival rate from lung cancer in this country is 15.5% according to the latest available information.

You can begin to see why so many people are excited by the results of this screening study.

But there are some cautionary notes that have to be considered before we jump in with both feet and recommend every smoker and former smoker at high risk go out and get a lung scan to screen for lung cancer.

As pointed out in an editorial in the same issue of the New England Journal, we have not yet defined who really is at high risk of developing lung cancer, and would benefit from this screening.  In fact, in this study, each participating group set its own criteria for entering someone into the trial.  Entry requirements were not uniform among all the participating centers.

The study was not a “gold standard” type of study, namely a controlled clinical trial which would definitively answer the question of whether or not the benefits observed would apply to large numbers of people generally screened and treated in community settings (although it should be noted that community hospitals were included in the currently reported trial).

As with every other screening program, we are going to find cancers that would otherwise not cause harm to the person because of the different ways different cancers behave.  This is particularly true of prostate cancer, but we haven’t had the technology or protocols available to us to even remotely consider such a situation with lung cancer.  What this means is that we might be finding many small, slow growing lung cancers that in the past we would have never known about and would not have caused the patient any harm.

The editorial writer also points out that tumors located in the central part of the lung are more difficult to see by lung CT scans.

In this study, many of the cancers that were detected were adenocarcinomas, which tend to located in the periphery of the lung.  In fact, 66% of the cancers were of this cell type.

In the past, when the previous screening trials were conducted, the majority of the lung cancers were of the squamous cell type which tend to be more centrally located.  Also, the percentage of small cell lung cancers—typically the most virulent lung cancer—in the current study represented only 16 of the 412 cancers, or close to 4%.  That is far less than was the case years ago.

One other comment in the actual study report that I noted was that “all participants were considered fit to undergo thoracic surgery.”

When you care for people who are at the highest risk for lung cancer, they generally tend to be older, have serious lung and heart disease among other medical conditions and are frequently not candidates for surgery.  That may explain why the surgical death rates for people treated for their lung cancer in this study who died within one month of their surgery was 0.5%, compared to the usual 1.0%.

That same requirement may have also excluded a number of people from the screening study who are at high risk of developing lung cancer, and may explain why so many of the cancers were stage I, when one might expect a larger number of people initially screened for lung cancer to have more advanced disease.

None of these comments, however, diminish the importance of this study.

First, it’s important to remember that the goal of this particular report was to update the survival expectations of people screened in this study. 

No one can ignore the fact that those survival statistics were outstanding, and far better than we could have anticipated.

Second, there are still other randomized trials underway which may shed more light on whether in fact mortality from lung cancer is reduced by screening in the community setting.  It may seem like some of us are setting the bar too high by waiting for the results of these trials, when the data is so encouraging from the study reported today.  But it is at times difficult to wait for the evidence to develop which will be (hopefully) more definitively supportive of this approach.

We have, after all, faced similar controversy with respect to prostate cancer screening. 

We have known that the death rates from prostate cancer have been decreasing.  Although it would appear that prostate cancer screening is responsible for this decline in mortality, not everyone is convinced.   There is a clinical trial in progress which we hope will answer the question definitively.

As a result, several major national associations and organizations do not recommend routine prostate cancer screening.  Instead, they say that the test should be offered to men along with information that will help them understand the benefits and the harms of prostate cancer screening, based on the best available evidence that we have today.

I suspect that is where we are heading with respect to lung cancer screening based on today’s report in the New England Journal.

Yes, there appears to be a real benefit in terms of survival for those screened according to the standards and protocols set up by these investigators.

No, not everyone would be eligible for screening based on the standards set up in this program.

But if you read or hear about the study, and if you read this blog and feel that you are interested in getting screened, and if you have a reasonable history of smoking (there is no guideline to tell you what the “right” history is where you would benefit from screening) which would put you at a high risk of lung cancer, then you should talk with your health care clinician about what your next steps would be.  (This is consistent with the current recommendations of the American Cancer Society.)

But we can’t tell you at this time what the “correct” smoking history would be for you to be screened, and we can’t tell you what the right age is for you to be screened, and we can’t tell you how often you should be screened (aside from expense for these scans, there is the other question about the amount of radiation you might be exposed to, especially if you were 50 years old and decided to get a scan every year.  We also don’t know what the best interval is between scans which has the best chance of picking up a lung cancer at an early stage).

There is undoubtedly going to be much discussion and dissection of the results of this study over the next several months.  It is premature at this point to say whether any organizations such as the American Cancer Society are going to change their current guidelines regarding lung cancer screening as a result of this report.  That will take time and expert consensus.

But there is no question that this well-done study will have a significant impact on the discussions and decisions that will be made by people at risk for lung cancer, their families and their clinicians.

All of us would welcome the opportunity to reduce deaths from lung cancer. 

Collectively, the experts have to guide us on the next steps regarding screening for lung cancer. 

The sooner we develop that information, the sooner we can provide needed guidance to the millions of smokers and former smokers in this country and around the world who will be anxiously awaiting our recommendations.

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Please note:  I am posting this from an airport with a poor internet connection.  In an effort to be timely with this blog (the embargo lifted at 5PM, I will be adding links at another time.

Thanks!

An announcement yesterday that Avastin (bevacizumab) was approved for the treatment of advanced lung cancer was good news, but it also raised some troubling questions.

How the company has responded to some of the criticisms about the cost of the drug is also of interest, but it remains to be seen how their efforts are going to be greeted by patients and their doctors.

First, the news about the treatment itself.

Lung cancer is the most common cause of cancer deaths in this country, accounting for about 167,000 deaths in 2006.

Unfortunately, over the past 30 years we haven’t made much progress in treating patients with lung cancer, especially when the disease is beyond surgical resection or has spread to other parts of the body. 

The likelihood of someone surviving lung cancer 5 years after diagnosis is 15.3% overall.   If the disease is localized, the chances are 49.5% for a five year survival, while for those who are diagnosed with distant disease the chances of living five years is a dismal 2.1%.

The history of the effectiveness of treating the most common form of lung cancer with chemotherapy hasn’t been very dramatic.

Years ago, when I started my training and practice in the 1970’s, it was evident that chemotherapy for this common form of lung cancer—called non-small cell lung cancer—didn’t do much for the patients I was treating. 

It actually came to the point where I would tell patients not to expect much from the chemotherapy, and in fact after detailed discussion there were those who elected not to proceed with further treatment.

As time went on, even the experts came to question the value of chemotherapy in the treatment of non-small cell lung cancer (patients with small cell lung cancer, although less common, did demonstrate some dramatic responses to chemotherapy, but cures remained elusive). 

This ultimately led to clinical trials comparing chemotherapy to “best available supportive care”.  These trials demonstrated that chemotherapy did provide some benefit in terms of survival, although the benefit was modest at best.

The next chapter in this story was to find out whether adding more drugs to the chemotherapy regimens improved survival, as well as measure the impact of more intense drug regimens on the quality of life.

The results of these trials showed that adding more and more drugs to the treatment of patients with this form of lung cancer did not meaningfully improve their survival.

The net result is that today we treat patients with advanced disease usually with two drugs, and when they progress beyond the initial treatment they are offered additional single agent therapy or one of the new targeted therapies called erlotinib (Tarceva).

Most patients don’t do very well on these drugs, with the exception of a small number of folks who respond dramatically to erlotinib.

So now we have a new addition to our armamentarium with the approval of Avastin (bevacizumab) to treat patients with advanced and/or recurrent non-squamous non-small cell cancer of the lung, when combined with chemotherapy.

But not everyone is going to benefit from this new treatment.  For example, patients with the squamous cell type of non-small lung cancer can’t receive the treatment because in the clinical trials there were significant problems with people coughing up blood during the treatment.

Squamous cell lung cancer accounts for about 20-25% of non-small cell lung cancers.

In addition, the estimated benefit of the increased survival seen in the clinical trial for patients treated with chemotherapy plus Avastin compared to those who received only chemotherapy was 2 months (from 10.3 to 12.3 months after the start of the treatment).

That is a very modest improvement in survival, but we need to remember that 50% of the patients who received Avastin in addition to their chemotherapy did worse than that, and 50% did better.  And, I suspect, among those who did better there may be some who had very significant improvements in their survival and their quality of life.

Despite this small increment, this new drug represents a significant improvement in survival for these patients. 

We cannot ignore that in other diseases, such as colorectal cancer, the improvements we see today compared to where we started 30 years ago are due in no small part to small, incremental steps over time.

In other words, the improvements we have seen in many difficult-to-treat cancers have come slowly, one step at a time.  They did not happen suddenly overnight.

That is the good news, so to speak.

What is the downside, aside from the expected and known side effects of the drug which are usually modest but can occasionally be severe?

The cost is substantial.

A press release from the company indicated that the monthly cost of the drug in treating advanced non-small lung cancer is $8800.  And that does not include the costs of the other drugs used in this regimen (carboplatin and paclitaxel).

This is double the cost of Avastin when it is used to treat colorectal cancer ($4400/month).

The reason for this discrepancy has raised questions in the medical community and elsewhere.  The explanation is simple: the dose of Avastin used in the lung cancer treatment program is much higher than the dose used to treat colorectal cancer.

According to the same press release, the company that makes the drug said the higher dose was indicated based on a clinical trial which found that it took more drug to get the benefit seen in lung cancer, compared to the lower dose which provided benefit to patients with colorectal cancer.

For the typical lung cancer patient, the average cost of Avastin treatment was $56,000, although it could be much higher if the physician has a patient who is doing well and she/he decides to continue the treatment (the National Comprehensive Cancer Network recommends 4-6 courses then stopping, although they also provide the option of continuing the therapy if the disease is stable).

In the same press release that announced the FDA approval, the company also said they were taking the step of limiting any patient’s cost for Avastin to a total of $55,000 in any one year. 

They wrote, “Genentech also announced today that the company plans to initiate a first-of-its-kind program to cap the overall expense of Avastin to $55,000 per year per eligible patient for any FDA approved indication.  The program will be available for eligible patients regardless of whether they are insured.  The company plans to launch the new program in January 2007.  In addition, the company announced that it has doubled its contribution to independent charities that provide so-pay assistance to a total of $50 million.”

So does that mean that everyone is going to be able to get this drug when they need it?

That remains the key question (or should I say the $64,000 question?).

Lung cancer disproportionately affects those who can least afford these types of drugs.  And even when someone has insurance or Medicare, the co-pays can be substantial.

I am already hearing stories about people who are turning down these newer drugs because of the cost.  Their concerns are not limited to affordability.  They don’t want to leave their survivors with the burden of an insurmountable debt.

There are no simple answers to these questions and these problems.  Advances in medicine are expensive.  To bring a drug like this to market costs over $1 billion today.  The risks are high, the returns uncertain, the manufacturing is tedious. 

Yet we are going to see more and more of these therapies become available over the next several years, and I suspect there are going to be some that produce remarkable responses for the patients who need them.

And we haven’t even begun to explore in any great degree the potential of mixing two or more of these targeted therapies—which may have different targets in the cancer cell—together.

But funds aren’t limitless.   Medicare and Medicaid already are facing significant budgetary problems, and when you consider that many cancer patients fall into the Medicare category you can understand why we are facing such difficult choices on how to sustain that system.

We can make progress, but inevitably we are going to have to face the cost of that progress.

In our American Cancer Society comments today, we said the following:

“There’s no question that bringing these drugs to market includes substantial investments    in    research, clinical trials, and manufacturing.  But their high costs can have an immediate and dramatic effect on cancer patients and their families.  These costs have the potential to reduce access to the best available treatment because families with limited incomes will be forced to make choices based on their finances.  Nonetheless, targeted therapies like Avastin that guild upon the substantial research of the past 30 years, supported by the ACS and others, point to the value of what can be accomplished over time with solid, basic research into the mechanisms of cancer.”

We find ourselves on the horns of a dilemma, and I don’t believe a $55,000 annual cap on costs is going to get us where we need to be.

I don’t have an answer to the problem, and I suspect there aren’t many others out there who do either.

But if we don’t figure out a way to make this work for more folks, we are going to end up in a situation where we may have miracles to offer, but no way to pay for them.

If we are going to make continued progress in reducing the burden of cancer, then we need to pay close attention to those lifestyle issues that impact cancer incidence, as well as make certain we get recommended cancer screenings at appropriate intervals.

But cancer prevention is not just a topic for adults like you and me. It should also be a topic for kids as well, particularly in the areas of smoking, diet, exercise and sun exposure.

We cannot ignore the fact that many of the habits that lead to cancer and other chronic illnesses start with our children, and we as adults and parents have a responsibility to our kids to set the right example, and to do our best to get them started on the right track.

In one area in particular, however, it looks like we are not doing a very good job, and that is in regards to the risks associated with sun exposure.

Skin cancer remains a serious problem in this country, and the data suggest that problem is increasing.  There are over 1 million “routine” skin cancers diagnosed in this country every year, and more than 62,000 cases of the more serious variety of skin cancer—melanoma—occur annually.

Although many skin cancers, called basal cell and squamous cell carcinomas, don’t lead to death, they can lead to serious medical problems resulting in extensive treatments and occasionally disfigurement.

So, although they are sometimes called “relatively benign,” I don’t believe that someone who has had or knows someone who has had one of these cancers that required extensive surgery would consider them so simple as to be called “benign”.

And, of course, we know that melanoma is a much more serious form of the disease that, in fact, can lead to death if not found early and properly treated.

What we do know is that the behaviors associated with skin cancer later in life start with our sun habits when we are young.    Sun exposure remains the primary cause of melanoma and other skin cancers.  Sunburns are a marker of excessive sun exposure, and sunburns remain a frequent event in the lives of young folks.

The bottom line: sunburn as a youth, skin cancer as an adult.  Not exactly a good combination.

But try convincing a 14 year old that considers themselves invincible (and thinks that age 60 is an eternity away in their lives) that their quest for the golden glow can be dangerous for their health, not to mention may leave them wrinkled and marked with splotches on their skin.  A tough task indeed.

That doesn’t mean that many groups, organizations and governmental agencies haven’t been trying.

How successful have their efforts been?

Not as successful as one would like, based on a recent report in the journal Pediatrics authored by some of my American Cancer Society colleagues.

In this study the authors did a telephone survey of 1613 parents/caregivers in 2004 about the sun safety behaviors of their children and compared the results to a prior survey done in 1998.  Their goal was to detect any changes in those behaviors.

They asked a number of questions, including questions about sun protection, the number of sunburns experienced, and attitudes toward sun exposure.

The findings were not, overall, particularly encouraging.

The number of sunburns experienced during the immediately previous summer remained almost identical between the two surveys (72% in 1998 and 69% in 2004).

For those who had a sunburn—close to 2 out of 3 children questioned—the average number of sunburns per child during the preceding summer was 3.1 in 1998 and 2.9 in 2004.

There was some good news, suggesting that among younger children the frequency of sunburns were fewer in 2004 than in 1998.

One of the disheartening findings of the current survey was that there was a positive relationship between the use of sunscreen and the odds of having a sunburn.

What that means in plain terms was that the kids who used a sunscreen had a greater chance of reporting they had a sunburn.

How could that be?  Isn’t sunscreen supposed to protect against sunburn?

This information suggests that the children are not using the sunscreen properly, and probably have a false sense of protection by not reapplying the sunscreen during the day, or after they sweat or go into the pool or the ocean.

It would appear that just because they use it doesn’t mean they follow the directions on the label.

There was an indication that more children were using sunscreen regularly in 2004 than in 1998 (39% vs. 31%) when going outside on a sunny day for more than one hour.

Other sun-safe behavior patterns did not change over the 6 years, such as wearing sunglasses, wearing protective clothing such as long sleeve shirts or long pants when outside of the sun (when was the last time you saw a young woman or man dressed like that on the beach?), or staying in the shade. 

Only 1 in 20 kids wore a wide-brimmed hat when outside in the sun.

There was a suggestion that more kids did take the sun protection message more seriously, but over 2/3 said they look better with a tan, and over half said they feel healthy when they have a tan.

So what does all this mean?

Despite our efforts to educate our youth about the risks of excessive sun exposure, we aren’t getting the job done.

The survey also found that days at the beach were increasing over the six year interval.

Together, this means that many years from now we will reap the benefits of our non-action in an increased number of people with skin cancer and melanoma.

And if the sunscreen message isn’t getting through to a significant number of children, then certainly the other sun-safety behavioral modification suggestions are doing even worse.

Other countries—particularly Australia—recognized the seriousness of the problem related to sun exposure many years ago.  As a result, they instituted extensive educational programs to educate their population about the risks of excessive sun exposure and the fact that it leads to skin cancer.

Because of this effort, Australians understand the meaning of the UV index, and they know how to incorporate that piece of information into their daily routines. They practice effective sun-safety.  As a consequence of these efforts, their incidence of skin cancer has declined because people have heeded the message.

I can’t say that I am particularly optimistic that we will be as successful as the Australians.  Clearly, the data from this survey suggests that our sun-safety education efforts are not producing meaningful results, especially among our youth.

The authors suggest that to accomplish this goal, “Research is needed on effective mechanisms to broadly diffuse skin cancer prevention intervention and sun-safety policies in communities and in schools and for effective ways to increase the role of pediatricians and health care providers with their patients about sun safety practices to minimize risks associated with excessive UV exposure.”

But how can we do that when it becomes obvious that people at the beach don’t understand that the red flag means stay out of the water?

When it comes to sun-safe behaviors--and prevention in general--we need to find a much better way to communicate with people.  We need to determine ways to persuade folks to really change behaviors and commit themselves to their health.

When we figure that out, we will all be much better off.