One of my favorite television shows right now is The Knick, as I described before in a post about medical history. To give you an idea of how much I’m into The Knick, I’ll tell you that I signed up for Cinemax for three months just for that one show. (After its second season finale airs next Friday, I’ll drop Cinemax until next fall.) The reason why I’m bringing up The Knick (besides I love the show and need to bring it up at least once a year) is because an article by Malcolm Gladwell in The New Yorker entitled “Tough Medicine“, which is a commentary based on a new book on cancer by a veritable god of cancer research, Vincent T. DeVita, Jr., immediately resonated with a storyline in this season of The Knick. I haven’t yet read The Death of Cancer: After Fifty Years on the Front Lines of Medicine, a Pioneering Oncologist Reveals Why the War on Cancer Is Winnable–and How We Can Get There by Vincent T. DeVita and Elizabeth DeVita-Raeburn, but I want to. I can tell, though, that there will be parts of the book I find annoying just from Gladwell’s take on it, which approvingly describes DeVita as railing against the cautiousness and incremental nature of today’s cancer research. To give you an idea of where Gladwell’s coming from, I note that his article shows up in the title bar of my web browser not as “Tough Medicine” but rather “How To Cure Cancer”, even as the title on the web page itself remains “Tough Medicine”. On the other hand, the article does conclude with Gladwell demonstrating a better understanding of the disadvantages of what DeVita is proposing than it seems that he will in the beginning. In fact, it is Gladwell who is more reasonable than his subject, although he does appear share DeVita’s apparent assumption that potentially all cancer patients are savable if only we try hard enough. (more…)
Archive for Cancer
American charlatan Brian Clement made another trip to Canada recently and was caught on audiotape claiming multiple sclerosis could be “reversed” at the Hippocrates Health Institute (HHI), where he serves as Director. This is yet another in a series of his misrepresentations about the effectiveness of the quack treatments offered at HHI. Indeed, Clement calls to mind the old joke about inveterate liars:
Q: Know how can you tell this guy is lying?
A: His lips are moving.
Once again, the Canadian Broadcasting Corporation (CBC), which has done an outstanding job exposing Clement and his mendacity, caught him in this particular fabrication. (The American media, by contrast, has largely ignored the story, even to the point of printing credulous puff pieces about Clement.) According to the CBC, it:
obtained a recording of a lecture Clement gave in September in Montreal where he said, “Last week, we had somebody at the institute that reversed multiple sclerosis.”
He went on to claim that many other people who visited his Florida spa, the Hippocrates Health Institute, saw similar results.
“A nurse that came to us two years ago was crippled, had braces on. By the time she left Hippocrates, she reversed the multiple sclerosis.
“And mainstream medicine, they think it’s remarkable. I’ve seen lots and lots of people over the years did that.”
The Truth About Cancer: A Global Quest is billed as “the documentary series the mainstream media refused to air.” It consists of eleven episodes and is produced by Ty Bollinger, an outspoken supporter of natural treatments for cancer. Episodes 1 and 2 are currently available online.
Ty Bollinger started his quest because several of his family members had died of cancer despite conventional cancer treatment. He believed they had died not of the cancer but of the cancer’s “so-called treatments” and “false treatments.” He doesn’t explain which cancers they had, what the treatments were, or why he calls them “false.” He was angry, and he wanted his relatives’ lives to matter; he thought he could give their deaths meaning by seeking out alternative treatments that would have saved them and could save others. He was an accountant and bodybuilder, untrained in science or medicine. He started out with the conviction that conventional cancer treatment was a fraud, and confirmation bias had a field day. Instead of learning about cancer from reliable sources, he avoided mainstream cancer experts and researchers and only interviewed alternative practitioners from all over the world who agreed with his premise. He eagerly swallowed everything they told him.
He says, “You are about to learn the best treatments and preventions to cancer, protocols that won’t harm your body, from the world leading doctors across the globe.” He promises to show viewers science and documented evidence. He promises to expose the lies of conventional cancer treatment. He thinks he has information that will eradicate cancer once and for all. He couldn’t be more wrong. (more…)
Gideon Burrows has an inoperable brain cancer that is slow growing but is inevitably going to kill him. He has written a remarkable book about his experience, This Book Won’t Cure Your Cancer. A professional wordsmith, he is able to describe his experience of illness so vividly that the reader enters into his life, feels what he feels, and shares his suspense about what the next scan or doctor’s visit will reveal. Along with him, we suffer through the panic and fear, the chaos, the agonies of delays and uncertainty, the unpleasant hospital environment, and specialists with poor bedside manners. We follow him through difficult decisions about how to share the bad news with friends, relatives, and his young children; and we understand why this engenders guilt feelings. The story is as engaging as a detective story; we can hardly wait to see what the next scan will show and how the story of his illness will play out. It puts a human face on the cancer experience, and it would be valuable for that alone, but it is much more. The gradually unfolding episodes of his personal story are interwoven with what amounts to a primer on how to think critically about science-based medicine vs. alternative treatments. I can’t recommend this book highly enough.
One of the things that feels the weirdest about having done the same job, having been in the same specialty, for a longer and longer time is that you frequently feel, as the late, great Yogi Berra would have put it, déjà vu all over again. This is particularly true in science and medicine, where the same issues come up again and again and again, often with the same arguments on either side. Sometimes the same players are even involved. So it is with mammography recommendations. Indeed, I’m feeling déjà vu all over again right now, as I read headlines like “Women advised to get mammograms later, less often“, “American Cancer Society, in a Shift, Recommends Fewer Mammograms“, and “ACS: Breast cancer screening should begin at age 45“. What provoked these headlines was a major revision in the American Cancer Society’s recommendation for mammographic screening for breast cancer in women at average risk of the disease. In a seeming replay from 2009, when the United States Preventative Services Taskforce (USPSTF) sent shockwaves through the breast cancer world by recommending that most women not start mammography until age 50 and then only to have it done every two years instead of every year, the American Cancer Society (ACS) has now just similarly ratcheted back its recommendations for screening mammography, just not as much as the USPSTF did. The new recommendations were communicated in a special communication published by JAMA on Tuesday.
What changed regarding mammography recommendations
Before we get to the issues, how, specifically, did the ACS change its mammography recommendations? Before this change, the ACS basically recommended the same thing that most other American professional societies dealing with breast cancer did: yearly mammography starting at age 40 for the rest of a woman’s life. The new guidelines now recommend that women with an average risk of breast cancer should undergo regular screening mammography starting at age 45 years and continuing annually until age 54. From age 55 and older, the ACS recommends that women transition to every two years. (More details below.) As I Tweeted when I saw these recommendations, basically it appears that the ACS has more or less split the difference between the old recommendations and the USPSTF recommendations.
So why is the ACS changing its recommendations? And what does this say about the science and our values regarding cancer screening? If you’ve been reading this blog, you know that over the last several years there has been a steady drip, drip, drip of studies that range from highlighting the downside of widespread mammographic screening to downright questioning the value of mammography. That’s why I’ve been discussing rethinking screening for breast cancer since at least 2008. Basically, you can go back and read my old posts and, if you have a lot of time and are enough of a glutton for punishment to read them all, watch the evolution of my thinking about breast cancer screening over the last seven years.
Back in the day, I used to fully support breast cancer screening beginning at age 40 and proceeding yearly throughout. As I examined more and more of the evidence, I became less enthusiastic about screening so intensely and started to believe that starting at 40 was too young for most women. Indeed, I was probably the only breast cancer doctor at my cancer center in 2009 who supported the USPSTF recommendations when they were announced, which led to some—shall we say?—interesting discussions about what should be said to the press and what a press release our cancer center wanted to release ASAP should actually say. I also got myself into a little…trouble…for criticizing colleagues in radiology—not from my institution, I hasten to add!—for some rather blatant turf protection. Let’s just say that a prominent radiologist, one who’s achieved far more renown in his field than I ever have in mine, was most displeased with some of my commentary and let me know about it. I found this displeasure odd, given that I am most definitely not a nihilist with respect to mammography screening (and, make no mistake, there are quite a few of those out there these days). I’m just a lot more balanced and aware of its limitations than I used to be. On the other hand, I did call him out for some of his more obnoxious comments that implied that those who question mammography are cackling gleefully at the thought of more women dying of breast cancer. Interestingly, I don’t seem to get asked to contribute to such press releases that much anymore, but in fairness neither do most of the other breast cancer clinicians I work with; so I probably can’t blame it on my previous outspokenness.
What brought me to this point is an increasing understanding of the concepts of overdiagnosis and lead time bias, coupled with a string of studies that show more modest benefits (and, in one case, no benefit) from screening mammography. To be honest, the attack dog reaction by some mammography supporters to some of these negative studies also set my skeptical antennae a’twitchin’ as well.
One of the more depressing topics that I regularly write about on this blog includes of analyses of news stories of children with cancer whose parents decided to stop science-based treatment (usually the chemotherapy) and use quackery instead. There are, of course, variations on this theme, but these stories take form that generally resembles this outline: A child is diagnosed with a highly treatable cancer with an excellent cure rate. Standard science-based treatment is begun, but the child suffers severe side effects from the chemotherapy. After an incomplete course of chemotherapy, the parents, alarmed at their child’s suffering, start balking at further chemotherapy, either because the child refuses further treatment or because they do. At some point in this process the parents become aware of the claims of practitioners of this or that alternative medicine, who tell them that their child’s cancer can be cured without toxic chemotherapy, and, wooed by the siren song of a promise of a cure without suffering, the parents choose that instead. At this point, physicians, alarmed at the parents’ choice, call in their state’s child protective services team, and a court battle ensues. Sometimes the court battle results in an order that the child complete conventional therapy, as it did with, for example, Daniel Hauser or Cassandra Callender. Sometimes it ends with a compromise in which the child and/or parents can choose an unconventional practitioner, as in the case of Abraham Cherrix. All too often the courts utterly fail to protect children with cancer, as the Canadian courts did in the cases of Makayla Sault and JJ. Not infrequently, if the court rules against the parents, the parents flee with their child to avoid treatment, as happened with Daniel Hauser, Abraham Cherrix, and Sarah Hershberger. Usually, they ultimately come back.
However they turn out, over the years of looking into them I’ve found that these stories tend to bear a depressing similarity and predictability. For example, if the child does well, it is always attributed to the alternative treatment, even when the child received a significant amount of conventional therapy. This attribution derives from a fundamental misunderstanding of how the treatment of cancer works in that the problem with incomplete cancer treatment is not that it can’t cure the cancer but that it has less of a chance of doing so. As I’ve explained many times, the reason that treatment regimens for many pediatric cancers involve two years’ worth of chemotherapy is that over time pediatric oncologists learned the hard way that, although the first cycle of chemotherapy (usually called induction chemotherapy) can lead to remission, without the additional cycles the chances of recurrence are very high—unacceptably so. Consequently, children who stop chemotherapy early can be in remission; they’ve just been put at a high risk of recurrence.
Presidential candidate Ben Carson: Shilling for Mannatech with his very own alternative cancer cure testimonial?
Over the years, mainly at my not-so-super-secret other blog, I’ve frequently made the points that the vast majority of physicians are not scientists and, in fact, that many of them suffer from a severe case of Dunning-Kruger when it comes to science outside of biomedical sciences—or even biomedical sciences outside of their medical field of expertise. The most common science I’ve seen physicians embarrass themselves attacking has generally been evolution, with a disturbingly high number of physicians denying evolution and embracing creationism. Of these, the doctor I wrote about most frequently back in the day was the creationist neurosurgeon Michael Egnor, but with the onset of the 2016 Presidential race there’s been a new creationist neurosurgeon in town with arguably even more ignorant attacks on evolution. I’m referring, of course, to noted neurosurgeon Ben Carson, whose creationist stylings have been so bad that I had to use him as a poster child to demonstrate how the vast majority of physicians are not scientists and all too many of us have an inordinate and unjustified confidence in medicine as a “check on BS.”
Over the last couple of weeks since my post on the second Republican debate, in which Donald Trump spewed antivaccine nonsense and Ben Carson pandered to antivaccine views, even though past statements by him demonstrate that he knows better, unfortunately Carson has continued to spew statements that are nothing but downright embarrassing, be they his statement in the wake of the Oregon mass shooting that it would be better to attack an armed gunman during a mass shooting “because he can’t get us all” (complete with a seeming attitude that those who died were cowardly), his doubling down on that by claiming that if the Jews had been armed maybe things would have turned out differently in the Holocaust (neglecting the fact that Jews did resist), or his many other statements that make me wonder how someone with so little critical thinking skills could get through medical school and a neurosurgery residency to become such a respected surgeon.
“Liquid biopsies” for cancer screening: Life-saving tests, or overdiagnosis and overtreatment taken to a new level?
I’ve written many times about how the relationship between the early detection of cancer and decreased mortality from cancer is not nearly as straightforward as the average person—even the average doctor—thinks, the first time being in the very first year of this blog’s existence. Since then, the complexities and overpromising of various screening modalities designed to detect disease at an early, asymptomatic phase have become a relatively frequent topic on this blog. Before that, on my not-so-super-secret other blog, I noted that screening MRI for breast cancer and whole body CT scans intended to detect other cancers early were not scientifically supported and thus were far more likely to cause harm than good. That was well over ten years ago. Now we have a company offering what it refers to as a “liquid biopsy” for the early detection of cancer. I fear that this is the recipe for the ultimate in overdiagnosis. I will explain.
The problem, of course, is that disease progression, including cancer progression, is not always a linear process, in which the disease progresses relentlessly through its preclinical, asymptomatic phase to symptoms to complications to (depending on the disease) death. There is such a thing as disease that remains asymptomatic and never progresses (at which point it’s hard to justify actually calling it a disease). As I pointed out in my first SBM post on the topic, at least three-quarters of men over 80 have evidence of prostate cancer in autopsy series. Yet nowhere near three-quarters of men in their 80s die of prostate cancer—or ever manifest symptoms from it. This is what is meant by overdiagnosis, the diagnosis of disease that doesn’t need to be treated, that would never cause a patient problems.
When teaching medical students and residents, I frequently emphasize that overdiagnosis is different from a false positive because overdiagnosis does diagnose an actual abnormality or disease. For example, ductal carcinoma in situ (DCIS) diagnosed by mammography leading to a biopsy is a real pathological abnormality; it is not a false positive. We just do not know which cases of DCIS will progress to cancer and which will not, leading to a question of how DCIS should be treated or at the very least whether we should treat it as aggressively as we do now, particularly given that the apparent incidence of DCIS has increased 16-fold since the 1970s, all of it due to mammographic screening programs and the increased diagnosis of DCIS and early stage breast cancer has not resulted in nearly as much of a decrease in the diagnosis of advanced stage breast cancer as one would expect if early diagnosis were having an impact in reducing the diagnosis of late stage disease.
Overdiagnosis would not be such an issue if it didn’t inevitably lead to overtreatment. DCIS, for instance, is treated with surgery, radiation, and anti-estrogen drugs. Early stage prostate cancer used to be treated with radical prostatectomy, but now more frequently with radiation. Many of these men and women didn’t actually need treatment. We just don’t know which ones. This is why over the last six or seven years a significant rethinking of screening for breast and prostate cancer has occurred. There has been a backlash, of course, but the rethinking seems to have taken hold.
Not everywhere, of course. (more…)
I am fortunate to have become a physician in a time of great scientific progress. Back when I was in college and medical school, the thought that we would one day be able to sequence the human genome (and now sequence hundreds of cancer genomes), to measure the expression of every gene in the genome simultaneously on a single “gene chip,” and to assess the relative abundance of every RNA transcript, coding and noncoding (such as microRNAs) simultaneously through next generation sequencing (NGS) techniques was considered, if not science fiction, so far off in the future as to be unlikely to impact medicine in my career. Yet here I am, mid-career, and all of these are a reality. The cost of rapidly sequencing a genome has plummeted. Basically, the first human genome cost nearly $3 billion to sequence, while recent developments in sequencing technology have brought that cost down to the point where the “$1,000 genome” is within sight, if not already here, as illustrated in the graph above published by the National Human Genome Research Institute. Whether the “$1,000 genome” is truly here or not, the price is down to a few thousand dollars. Compare that to the cost of, for instance, the OncoType DX 21-gene assay for estrogen receptor-positive breast cancer, which costs nearly $4,000 and is paid for by insurance because its results can spare many women from even more expensive chemotherapy.
So, ready or not, genomic medicine is here, whether we know enough or not to interpret the results in individual patients and use it to benefit them, so much so that President Obama announced a $215 million plan for research in genomic mapping and precision medicine known as the Precision Medicine Initiative. Meanwhile, the deeply flawed yet popular 21st Century Cures bill, which passed the House of Representatives, bets heavily on genomic research and precision medicine. As I mentioned when I discussed the bill, it’s not so much the genomic medicine funding that is the major flaw in the bill but rather its underlying assumption that encouraging the FDA to decrease the burden of evidence to approve new drugs and devices will magically lead to an explosion in “21st century cures,” the same old antiregulatory wine in a slightly new bottle. Be that as it may, one way or the other, the federal government is poised to spend lots of money on precision medicine.
Because I’m a cancer doctor, and, if there’s one area in medicine in which precision medicine is being hyped the hardest, it’s hard for me not to think that the sea change that is going on in medicine really hit the national consciousness four years ago. That was when Walter Isaacson’s biography of Steve Jobs revealed that after his cancer had recurred as metastatic disease in 2010. Jobs had consulted with research teams at Stanford, Johns Hopkins, and the Broad Institute to have the genome of his cancer and normal tissue sequenced, one of the first twenty people in the world to have this information. At the time (2010-2011), each genome sequence cost $100,000, which Jobs could easily afford. Scientists and oncologists looked at this information and used it to choose various targeted therapies for Jobs throughout the remainder of his life, and Jobs met with all his doctors and researchers from the three institutions working on the DNA from his cancer at the Four Seasons Hotel in Palo Alto to discuss the genetic signatures found in Jobs’ cancer and how best to target them. Jobs’ case, as we now know, was a failure. However much Jobs’ team tried to stay one step ahead of his cancer, the cancer caught up and passed whatever they could do. (more…)
I’ve written more times than I can remember about the phenomenon of overdiagnosis and the phenomenon that is linked at the hip with it, overtreatment. Overdiagnosis is a problem that arises when large populations of asymptomatic, apparently healthy people are screened for a disease or a condition, the idea being that catching the disease at an earlier stage in its progression will allow for more successful treatment. Two prominent examples include—of course—screening for breast cancer with mammography and screening for prostate cancer with prostate-specific antigen (PSA) testing, and I’ve written about the problem of overdiagnosis with each of them on many occasions. Basically, overdiagnosis occurs when the screening test picks up what we call “preclinical” disease (i.e., disease that hasn’t become symptomatic) that, if left untreated, would never become symptomatic or endanger the health or life of the patient). Although intuitively, it seems to the lay public (and, truth be told, most doctors) that detecting cancer earlier must be inherently better, it turns out that it’s way more complicated than you think. There is a price to be paid for early diagnosis in the form of overtreatment of disease that doesn’t need treatment and for disease that is destined to threaten the life of the patient earlier treatment doesn’t always result in better outcomes. Also, whenever you screen for a condition in asymptomatic people, you will always—always—find much more of it, and the significance of those added diagnoses is not always clear, as a new study in JAMA Oncology shows.
DCIS and mammography: Some background
Before I get to the meat of the study, from my perspective, nowhere is the problem of overdiagnosis and overtreatment in cancer screening as pronounced than in the condition known as ductal carcinoma in situ (DCIS). DCIS is commonly referred to as “stage 0” breast cancer and is characterized by milk duct cells that appear malignant but remain confined to the milk ducts. In other words, they haven’t invaded the tissue surrounding the ducts. In general, DCIS is treated similarly to breast cancer, with surgical excision, either by mastectomy or breast-conserving surgery, followed by radiation therapy if breast conserving surgery is used. Then, depending on its hormone receptor status, adjuvant treatment consists of blocking estrogen for five years. The rationale for this treatment is the view of DCIS as being a precursor to fully invasive breast cancer and that treating the DCIS will prevent the development of breast cancer. Over the last couple of decades, however, it has become clear that not all DCIS is created equal. Much of it will never progress to breast cancer in the lifetime of the woman (particularly if the woman is older, which means less time for fully malignant transformation to occur). Evidence suggesting this includes studies showing an increase in DCIS incidence by 16-fold since the 1970s, when mammography started to be introduced on a large scale, with little change in the incidence of invasive cancer. Today, 20-25% of mammography-detected breast cancer diagnoses are DCIS; forty years ago, DCIS was an uncommon diagnosis, except associated with an invasive cancer.