Preface: On issues such as this, I think it’s always good for me to emphasize my disclaimer, in particular:
Dr. Gorski must emphasize that the opinions expressed in his posts on Science-Based Medicine are his and his alone and that all writing for this blog is done on his own time and not in any capacity representing his place of employment. His views do not represent the opinions of his department, university, hospital, or cancer institute and should never be construed as such. Finally, his writings are meant as commentary only and are therefore not meant to be used as specific health care recommendations for individuals. Readers should consult their physicians for advice regarding specific health problems or issues that they might have.
Now, on to the post…
“Early detection saves lives.”
Remember how I started a post a year and a half ago starting out with just this statement? I did it because that is the default assumption and has been so for quite a while. It’s an eminently reasonable-sounding concept that just makes sense. As I pointed out a year and a half ago, though, the question of the benefits of the early detection of cancer is more complicated than you think. Indeed, I’ve written several posts since then on the topic of mammography and breast cancer, the most recent of which I posted a mere two weeks ago. As studies have been released and my thinking on screening for breast cancer has evolved, regular readers have had a front row seat. Through it all, I hope I’ve managed to convey some of the issues involved in screening for cancer and just how difficult they are. How to screen for breast cancer, at what age to begin screening, and how to balance the benefits, risks, and costs are controversial issues, and that controversy has bubbled up to the surface into the mainstream media and public consciousness over the last year or so.
This week, all I can say is, “Here we go again”; that is, between downing slugs of ibuprofen for the headaches some controversial new guidelines for breast cancer screening are causing many of us in the cancer field.
I see that the kerfuffle over screening for cancer has erupted again to the point where it’s found its way out of the rarified air of specialty journals to general medical journals and hence into the mainstream press.
Over the last couple of weeks, articles have appeared in newspapers such as the New York Times and Chicago Tribune, radio networks like NPR, and magazines such as TIME Magazine pointing out that a “rethinking” of routine screening for breast and prostate cancer is under way. The articles bear titles such as A Rethink On Prostate and Breast Cancer Screening, Cancer Society, in Shift, Has Concerns on Screenings, Cancers Can Vanish Without Treatment, but How?, Seniors face conflicting advice on cancer tests: Benefit-risk questions lead some to call for age cutoffs, and Rethinking the benefits of breast and prostate cancer screening. These articles were inspired by an editorial published in JAMA last month by Laura Esserman, Yiwey Shieh, and Ian Thompson entitled, appropriately enough, Rethinking Screening for Breast Cancer and Prostate Cancer. The article was a review and analysis of recent studies about the benefits of screening for breast and prostate cancer in asymptomatic populations and concluded that the benefits of large scale screening programs for breast cancer and prostate cancer tend to be oversold and that they come at a higher price than is usually acknowledged.
For regular readers of SBM, none of this should come as a major surprise, as I have been writing about just such issues for quite some time. Indeed, nearly a year and a half ago, I first wrote The early detection of cancer and improved survival: More complicated than most people think. and then followed it up with Early detection of cancer, part 2: Breast cancer and MRI. In these posts, I pointed out concepts such as lead time bias, length bias, and stage migration (a.k.a. the Will Rogers effect) that confound estimates of benefit due to screening. (Indeed, before you continue reading, I strongly suggest that you go back and read at least the first of the aforementioned two posts to review the concepts of lead time bias and length bias.) Several months later, I wrote an analysis of a fascinating study, entitling my post Do over one in five breast cancers detected by mammography alone really spontaneously regress? At the time, I was somewhat skeptical that the number of breast cancers detected by mammography that spontaneously regress was as high as 20%, but of late I’m becoming less skeptical that the number may be somewhere in that range. Even so, at the time I did not doubt that there likely is a proportion of breast cancers that do spontaneously regress and that that number is likely larger than I would have guessed before the study. Of course, the problem is that we do not currently have any way of figuring out which tumors detected by mammography will fall into the minority that do ultimately regress; so we are morally obligated to treat them all. My most recent foray into this topic was in July, when I analyzed another study that concluded that one in three breast cancers detected by screening are overdiagnosed and overtreated. That last post caused me the most angst, because women commented and wrote me asking me what to do, and I had to answer what I always answer: Follow the standard of care, which is yearly mammography over age 40. This data and these concerns have not yet altered that standard of care, and I am not going to change my practice or my general recommendations to women until a new consensus develops.
Screening for disease is a real pain. I was reminded of this by the publication of a study in BMJ the very day of the Science-Based Medicine Conference a week and a half ago. Unfortunately, between The Amaz!ng Meeting and other activities, I was too busy to give this study the attention it deserved last Monday. Given the media coverage of the study, which in essence tried to paint mammography screening for breast cancer as being either useless or doing more harm than good, I thought it was imperative for me still to write about it. Better late than never, and I was further prodded by an article that was published late last week in the New York Times about screening for cancer.
If there’s one aspect of medicine that causes more confusion among the public and even among physicians, I’d be hard-pressed to come up with one more contentious than screening for disease, be it cancer, heart disease, or whatever. The reason is that any screening test is by definition looking for disease in an asymptomatic population, which is very different from looking for a cause of a patient’s symptoms. In the latter case, the patient is already being troubled by something that is bothering him. There may or may not be a cause in the form of a disease or syndrome that is responsible for the symptoms, but the very existence of the symptoms clues the physician in that there may be something going on that requires treatment. The doctor can then narrow down range of possibilities for what may be the cause of the patient’s symptoms by taking a careful history and physical examination (which will by themselves most often lead to the diagnosis). Diagnostic tests, be they blood tests, X-rays, or other tests, then tend to be more confirmatory of the suspected diagnosis than the main evidence supporting a diagnosis.
It’s easy to think of medical tests as black and white. If the test is positive, you have the disease; if it’s negative, you don’t. Even good clinicians sometimes fall into that trap. Based on the pre-test probability of the disease, a positive test result only increases the probability by a variable amount. An example: if the probability that a patient has a pulmonary embolus (based on symptoms and physical findings) is 10% and you do a D-dimer test, a positive result raises the probability of PE to 17% and a negative result lowers it to 0.2%.
Even something as simple as a throat culture for strep throat can be misleading. It’s possible to have a positive culture because you happen to be an asymptomatic strep carrier, while your current symptoms of fever and sore throat are actually due to a virus. Not to mention all the things that might have gone wrong in the lab: a mix-up of specimens, contamination, inaccurate recording…
Mammography is widely used to screen for breast cancer. Most patients and even some doctors think that if you have a positive mammogram you almost certainly have breast cancer. Not true. A positive result actually means the patient has about a 10% chance of cancer. 9 out of 10 positives are false positives.
But women don’t just get one mammogram. They get them every year or two. After 3 mammograms, 18% of women will have had a false positive. After ten exams, the rate rises to 49.1%. In a study of 2400 women who had an average of 4 mammograms over a 10 year period, the false positive tests led to 870 outpatient appointments, 539 diagnostic mammograms, 186 ultrasound examinations, 188 biopsies, and 1 hospitalization. There are also concerns about changes in behavior and psychological wellbeing following false positives.
Until recently, no one had looked at the cumulative incidence of false positives from other cancer screening tests. A new study in the Annals of Family Medicine has done just that. (more…)
You’ve all heard the dramatic testimonials in the media: “I had a PSA test and they found my prostate cancer early enough to treat it. The test saved my life. You should get tested too.” The subject of screening tests is one that confuses the public. On the surface, it would seem that if you can screen everyone and find abnormalities before they become symptomatic, only good would result. That’s not true. Screening tests do harm as well as good, and we need to carefully consider the trade-offs.
About half of American men over the age of 50 have had a PSA (prostate-specific antigen) screening test for prostate cancer. Recommendations for screening vary. The US Preventive Services Taskforce (USPSTF) says there is insufficient evidence to recommend screening. The American Urological Association and the American Cancer Society recommend screening. Urologists practice what they preach: 95% of male urologists over the age of 50 have been screened. But other groups like the American Academy of Family Physicians recommend discussing the pros and cons of screening with patients and letting them make an informed choice.
Two recent studies published simultaneously in The New England Journal of Medicine have added to the controversy. One concluded that screening does not reduce deaths from prostate cancer; the other concluded that it reduces deaths by 20%. (more…)
Thankfully, I don’t receive all that much blog-related mail. But this weekend I received several communications about a piece in popular liberal blog. The piece is (ostensibly) about Lyme disease, which coincidentally happens to be one of the topics of my first post here at SBM. In fact, I’ve written about Lyme disease a number of times, and Dr. Novella has a very good summary of the controversy at one of his other blogs. Since we’ve discussed this so many times, I won’t be reviewing the entire controversy, but looking at this particular blog post to examine how our personal experiences and errors in reasoning can distort our view of reality.
The topic of Lyme disease has come up recently in the press, and as the weather improves, cases in the northeastern U.S. should start to increase soon. Just as a reminder, so-called “chronic” Lyme disease is not Lyme disease at all. Lyme disease can have early and late manifestations, none of which correspond to the vague, protean symptoms labeled as “chronic” by some. The disease is often diagnosed without resort to objective evidence, such as reliable, positive lab tests. But let’s look at the blog post in question and see what’s there.
Last Wednesday, right before the four-day Thanksgiving holiday weekend, as I was far more interested in preparing to have family over the next day than in what was going on in the medical news or the blogs, the results of a most fascinating study hit the news. In Medscape, the title of the news report was Mammography Study Suggests Some Breast Cancer May Spontaneously Regress; on WebMD, the story ran under the title Can Breast Cancer Disappear?; on Medical News Today, Mammograms May Identify Cancers That Would Otherwise Just Regress by Drs. Per-Henrik Zahl, Jan Maehlen, and H. Gilbert Welch. Not surprisingly, the study found its way out of the medical news and into mainstream media outlets as well, given how provocative the findings seemingly are. From the Medscape report on this study:
A mammography study from Norway has come up with the controversial proposal that one fifth of breast cancer detected on screening may spontaneously regress. But there is no easy way to verify whether this is the case, say experts.
The study was published in the November 24 issue of the Archives of Internal Medicine. It found that the cumulative incidence of invasive breast cancer in a cohort of women, aged 50 to 64 years, who received 3 mammograms over 6 years was 22% higher than in a control group of age-matched women who received only 1 mammogram at the end of a 6-year period.
In their review of possible explanations for the difference in the breast cancer rates between the 2 groups — which had similar risk factors for breast cancer — the researchers write that the “natural course for some screen-detected breast cancers may be to spontaneously regress.”
“I anticipate that many clinicians will react negatively to the possibility of spontaneous regression, said coauthor Jan Maehlen, MD, PhD, professor of pathology at the Ulleval University Hospital, in Oslo, Norway, in an interview with Medscape Oncology.
Before I discuss the study itself, let me briefly discuss why clinicians may have a bit of a problem with the implications of this study, if they accurately reflect the biology of breast cancer.
Sometimes diagnosis is straightforward. If a woman has missed several periods and has a big belly with a fetal heartbeat, it’s pretty easy to diagnose pregnancy. But most of the time diagnosis is much more difficult. Alzheimer’s can’t be diagnosed for sure until the patient dies and you do an autopsy. If only we had one of those Star Trek gadgets to point at our patients and give us a quick and accurate answer! Alas! We are far from perfect. All too often, we really have no idea what’s causing a patient’s symptoms. We do a complete workup and still don’t know. What then?
We all know people who have symptoms that a series of doctors have failed to diagnose, who continue to doctor-shop, hoping to find that one doctor somewhere who will find something the others have missed. Occasionally they do; but far more often these people spend a great deal of time and money chasing a will-o’-the-wisp. Sometimes as they are searching, the illness gradually runs its course and goes away. When this happens, whatever they tried last gets the undeserved credit for the “cure.” Sometimes the symptoms persist and these searches consume their life, encourage unhealthy self-absorption, and permanently ensconce them in the “sick” role.
One of the attractions of alternative medicine is that it offers far more certainty than scientific medicine. If your scientific doctor can’t see anything on x-rays, your chiropractor can. He’ll tell you he knows exactly what’s wrong: a subluxation that he can fix. Sherry Rogers will tell you all illness is due to toxins accumulating in your cells and you must “detoxify or die.” Hulda Clark will tell you it’s all parasites that she can eliminate with her magic zapper. Robert Young says the cause of all disease is acidosis. They all have confident, precise answers. Wrong ones.
The One Cause of All Disease?
It’s really easy to figure out what’s causing a patient’s symptoms if you believe there is one simple cause for all disease. While I was writing this I got sidetracked and searched the Internet for “the one cause of all disease.” I found a lot of them, including: (more…)