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man using an asthma inhaler, treated for asthma Another study finding overdiagnosis (diagnosing something that isn't likely to cause problems) and misdiagnosis (diagnosing something that isn't there) which leads to overtreatment (unnecessary treatment) - this time of asthma in adults. A new study found that as many as 1 in 3 adults diagnosed with asthma may not actually have the disease. Was this due to spontaneous remission or to initial misdiagnosis? After all, many other diseases mimic the symptoms of asthma, and there is no test that can diagnose asthma with 100% accuracy. The study authors thought that of the 33% without asthma - that many of the adults had been originally misdiagnosed, while others had gone into remission. Excerpts from the thought-provoking site Health News Review:

Is it asthma? Many diagnosed with condition receiving unnecessary or incorrect treatment

As many as 1 in 3 adults diagnosed with asthma may not actually have the disease, according to new research published in the Journal of the American Medical Association (JAMA). Canadian researchers evaluated 613 patients with physician-diagnosed asthma and found that 203 participants (33%) most likely did not have the disease. After an additional 12 months of follow-up of this latter group, 181 subjects (30%) continued to exhibit no clinical or laboratory evidence of asthma.

This study, and its accompanying editorials, hit on a theme we’ve often raised with regard to cancer and many other chronic diseases: overdiagnosis leading to overtreatment. But it also raises the specter of misdiagnosis from the get-go, which can lead to erroneously treating a condition that isn’t there. The Canadian results may also confuse many of us who have grown accustomed to news stories warning us that asthma is on the rise. So which is it? More asthma which needs more aggressive treatment or less asthma warning against overtreatment?

“I think asthma is both overdiagnosed and underdiagnosed,” says Dr. Nancy Ott, an allergy and immunology specialist in practice for 28 years. “We don’t have a specific test that is definitive for asthma, and the diagnosis is nuanced. You need to look at the symptoms, the patient’s history, their family history, and the objective tests collectively. And I think we need to be much more strict in what constitutes asthma because the symptoms alone overlap with so many other conditions.”

This is not a message we hear nearly enough in news stories: the diagnosis of asthma, although common, is anything but cut-and-dried. In outpatient clinics – where most asthma is diagnosed – time pressures can lead to incomplete evaluations, which lead to misdiagnoses (which, by the way, includes over-, under-, and no diagnoses), and this can ultimately lead to patients suffering physically, emotionally and financially.

“We think that a large proportion of them had been misdiagnosed in the first place and another proportion that (was) a bit smaller had actually gone into remission, their asthma was no longer active,” said principal investigator Dr. Shawn Aaron, head of respirology at the University of Ottawa. Medical textbooks say about six per cent of people with asthma go into remission over a 10-year period, said Aaron. “But we found at least 20 per cent had gone into remission.” However, “one of the main messages I want to get across is that some people are being misdiagnosed because they’re not being properly investigated to begin with,” he said from Ottawa.

Which brings up an important point: the symptoms of asthma overlap with several other diseases. In the Canadian study, 12 people, or 2 percent of the participants, had serious conditions other than asthma, like heart disease and pulmonary hypertension. Others had problems such as hyperventilation from panic attacks, and gastroesophageal reflux (GERD). These latter two conditions frequently mimic asthma. As does vocal cord dysfunction. Suffice to say that if you were to take each of the classic symptoms of asthma individually, the list of diseases associated with that symptom is well over a dozen.

 Another large study looking at screening mammograms for breast cancer has raised the issue of overdiagnosis and overtreatment once again. The purpose of mammography screening is to find cancer when it is small and so prevent cancer from growing and becoming advanced cancer. However, the researchers did not find this - there was a major increase in finding small cancers (the kind that may grow so slowly as to never cause any problems or that may even regress), but the rate of advanced cancers stayed the same.

The problem of overdiagnosis (finding small tumors that may never cause problems) and overtreatment (treating unnecessarily), which is leading to medical experts "rethinking cancer screening" is a major shift in how cancer screening is being viewed for a number of cancers. This is because studies show that overall death rates are basically the same in screened vs non-screened persons for mammography, colon, prostate, and lung cancer screening (see post). The view of how cancer grows and spreads may have to be reexamined and changed. One possibility suggested by Dr. H. Gilbert Welch is that aggressive cancer is already "a systemic disease by the time it's detectable" (Oct. 28, 2015 post).

The following excerpts are from the thoughtful review of the study in Health News Review: Overdiagnosis of ductal carcinoma in situ: ‘the pathology equivalent of racial profiling’

Danish researchers are providing new evidence that many breast cancers found via screening mammograms don’t need to be treated. Women with these non-threatening tumors are said to be “overdiagnosed” with breast cancerOverdiagnosis occurs when breast screening such as mammography detects small, slow-growing cancers that may never cause the patient any trouble. Yet, women diagnosed with such tumors are exposed to very real harms–possible surgery, chemotherapy, radiation, and living life as a “cancer patient.”

How much overdiagnosis are we talking about? If you don’t include cases of ductal carcinoma in situ (DCIS) in the tallies, anywhere from 14.7% to 38.6% of breast cancers found via screening represent overdiagnosis, the study authors found. The rate ranges from 24.4% to as high as 48.3% when DCIS is included.

DCIS is a collection of abnormal cells inside a milk duct that may–but usually doesn’t–break out to become invasive and potentially lethal cancer. About 60,000 women are told they have DCIS each year in the United States. Some experts estimate that up to 80% of women with DCIS found via screening may not need any treatment at all–and instead should just keep an eye on things. Obviously, women need to be fully and accurately informed about the benefits and risks — including the risk of overdiagnosis — before embarking on any decision to get screened for breast cancer or choosing a course of action following a diagnosis.

Otis Brawley, MD, Chief Medical Officer for the American Cancer Society, says it’s been difficult for modern medicine to wrap its brain around the concept of overdiagnosis. The natural inclination is to assume that cancerous-looking cells “will grow, spread, and eventually kill,” he writes in an editorial accompanying the Danish study. “However, some of these lesions may be genomically predetermined to grow no further and may even regress. In many respects, considering all small breast lesions to be deadly and aggressive types of cancer is the pathologic equivalent of racial profiling.

Excerpts from the original study from the Annals of Internal Medicine: Breast Cancer Screening in Denmark: A Cohort Study of Tumor Size and Overdiagnosis

Background: Effective breast cancer screening should detect early-stage cancer and prevent advanced disease. Objective: To assess the association between screening and the size of detected tumors and to estimate overdiagnosis (detection of tumors that would not become clinically relevant).... Setting: Denmark from 1980 to 2010. Participants: Women aged 35 to 84 years. Intervention: Screening programs offering biennial mammography for women aged 50 to 69 years beginning in different regions at different times.

Conclusion: Breast cancer screening was not associated with a reduction in the incidence of advanced cancer. It is likely that 1 in every 3 invasive tumors and cases of DCIS (ductal carcinoma in situ) diagnosed in women offered screening represent overdiagnosis (incidence increase of 48.3%).

Breast screening is associated with a substantial increase in the incidence of nonadvanced tumors and DCIS (ductal carcinoma in situ) in Denmark but not with a reduction in the incidence of advanced tumors, and the overdiagnosis rate is substantial. These findings support that screening has not accomplished the promise of a reduction in invasive therapy or disease-specific mortality.

 The problem of overdiagnosis and overtreatment has been discussed in a number of posts on this site. And back in April 15, 2016 I posted that a type of noninvasive thyroid cancer had just been reclassified as a noncancer. Now a study in the prestigious New England Journal of Medicine finds that looking at 12 countries (including the USA): "Overall, we estimate that more than 470,000 women and 90,000 men may have been overdiagnosed with thyroid cancer over two decades in these 12 countries..."

The researchers further state that the "vast majority" of these patients received a diagnosis of small, low-risk papillary carcinomas, and they underwent surgery and other treatments, but these interventions have not shown "benefits in terms of improved survival". In fact, studies show that watchful waiting is just as effective. From Medscape:

Thyroid Cancer Overdiagnosis in Half a Million Patients

A large fraction of thyroid cancer cases represent overdiagnoses, and at least half a million patients, most of them women, may have received unnecessary surgery and other cancer treatments, say researchers from the the International Agency for Research on Cancer (IARC), in Lyons, France.

Their warning about an epidemic of thyroid cancer overdiagnosis comes from an analysis of cancer registry data from 12 countries published August 17 in the New England Journal of Medicine . Salvatore Vaccarella, PhD, and colleagues at the IARC estimate that more than 470,000 women and 90,000 men may have been overdiagnosed withthyroid cancer in 12 "high-income" countries (Australia, Denmark, England, Finland, France, Italy, Japan, Norway, Republic of Korea, Scotland, Sweden, and the United States) from 1987 to 2007.

Most of these thyroid cancers were small, low-risk papillary carcinomas, they note. The "vast majority" of these patients underwent total thyroidectomy, and a "high proportion" also received neck lymph-node dissection and radiotherapy, but these interventions do not have "proven benefits in terms of improved survival," the researchers point out...."However, if we take the most recent available period, 2003 - 2007, as typical of current practice, we estimate that overdiagnosis in women accounts for 90% of thyroid-cancer cases in South Korea; 70 to 80% in the United States, Italy, France, and Australia; and 50% in Japan, the Nordic countries, and England and Scotland."

The overdiagnosis is blamed on increasing medical surveillance and the introduction of new diagnostic techniques, such as neck ultrasonography (since the 1980s) and, more recently, CTscanning and MRI. This new technology has led to the detection of a large number of indolent, nonlethal diseases that exist in abundance in the thyroid gland of healthy people of any age, the researchers comment, adding that most of these tumors are very unlikely to cause symptoms or death....."It is fair to say that the large number of thyroid cancers being diagnosed represent an epidemic of diagnosis, or an epidemic of medical testing, rather than an epidemic of true disease."

These results also mean that most patients are receiving treatment that does not benefit them and that subjects them to risks of injury to the voice, permanent hypoparathyroidism, as well as the attendant risks of radioactive iodine treatment, he pointed out.  

The researchers caution against systematic screening for thyroid cancer and overtreatment of nodules <1 cm. "Watchful-waiting approaches should be considered a research priority and a preferable option for patients with low-risk papillary thyroid cancers," they say. Studies from Japan suggest that immediate surgery and watchful waiting are equally effective in preventing mortality, Dr Vaccarella said. One study showed that of 1235 patients with papillary microcarcinomas, only 3.5% experienced clinical progression of disease during a 75-month follow-up, and there were no deaths.

At Memorial Sloan Kettering Cancer Center, active surveillance has been offered to patients with low-risk, small, intrathyroidal cancers for several years, Dr Morris said. "Our results have mirrored the Japanese results, and fewer than 5% of patients end up showing any signs of tumor growth under close observation," he said.

 For the first time ever, one type of cancer has been reclassified as a non-cancer. An international panel of pathologists and clinicians has reclassified a type of thyroid cancer to reflect that it is noninvasive and has a low risk for recurrence.The panel renamed encapsulated follicular variant of papillary thyroid carcinoma (EFVPTC) as noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP). There has been concern for a while of the costs (financial, physical, and mental) of the overdiagnosis and overtreatment for something that won't spread (it's "indolent" and "low-risk").

There have been discussions for some time now in the medical community regarding the move away from the word "cancer" in the description of early stages of both breast and prostate cancer. In 2013, a medical team sanctioned by the National Cancer Institute proposed that a number of premalignant conditions, including ductal carcinoma in situ and high-grade prostatic intraepithelial neoplasia, should no longer be called "cancer." Instead, the conditions should be labeled something more appropriate, such as indolent lesions of epithelial origin (IDLE), the group suggested. " Use of the term 'cancer' should be reserved for describing lesions with a reasonable likelihood of lethal progression if left untreated," the group said at the time.

From Futurity: NONINVASIVE THYROID ‘CANCER’ ISN’T CANCER

The reclassification of a noninvasive type of thyroid cancer that has a low risk of recurrence is expected to reduce the fears and the unnecessary interventions that come with a cancer diagnosis, experts say. The incidence of thyroid cancer has been rising partly due to early detection of tumors that are indolent or non-progressing, despite the presence of certain cellular abnormalities that are traditionally considered cancerous, says senior investigator Yuri Nikiforov, professor of pathology at the University of Pittsburgh.

“This phenomenon is known as overdiagnosis,” Nikiforov says. “To my knowledge, this is the first time in the modern era a type of cancer is being reclassified as a non-cancer. I hope that it will set an example for other expert groups to address nomenclature of various cancer types that have indolent behavior to prevent inappropriate and costly treatment.”

In particular, a tumor type known as encapsulated follicular variant of papillary thyroid carcinoma (EFVPTC) has increased in incidence by an estimated two- to three-fold over the past 20 to 30 years and makes up 10 to 20 percent of all thyroid cancers diagnosed in Europe and North America. Although studies have shown EFVPTC is not dangerous, it is typically treated as aggressively as other types of thyroid cancer. At the recommendation of the National Cancer Institute, the panel sought to revise the terminology and to see if the word “cancer” could be dropped from its name.

As reported in JAMA Oncology, two dozen experienced pathologists from seven countries and four continents independently reviewed 268 tumor samples diagnosed as EFVPTC from 13 institutions....In a group of more than 100 noninvasive EFVPTCs, there were no recurrences or other manifestations of the disease at a median follow-up of 13 years. They decided to rename EFVPTC as “noninvasive follicular thyroid neoplasm with papillary-like nuclear featuresor NIFTP. The new name cites key features to guide pathologists in diagnosis, but omits the word “cancer,” indicating that it need not be treated with radioiodine or other aggressive approaches.

“We determined that if NIFTP is carefully diagnosed, the tumor’s recurrence rate is extremely low, likely less than 1 percent within the first 15 years,” Nikiforov says. “The cost of treating thyroid cancer in 2013 was estimated to exceed $1.6 billion in the US. Not only does the reclassification eliminate the psychological impact of the diagnosis of ‘cancer,’ it reduces the likelihood of complications of total thyroid removal, and the overall cost of health care.”

The issue of overdiagnosis and overtreatment rears its head again - this time in a study looking at thyroid cancer detection and death rates. The death rate from thyroid cancer has stayed the same since 1935, as has the number of thyroid cancers presenting with symptoms of thyroid cancer. But...the number of new cases of silent thyroid cancer -- the kind where patients have no symptoms -- almost quadrupled in recent years, and these are the tiny cancers that probably won't cause a problem in the person's lifetime. The researchers then discuss how NOT to find these tiny silent thyroid cancers, so as to avoid overdiagnosis and the harms of overtreatment. From Science Daily:

Increased detection of low-risk tumors driving up thyroid cancer rates, study finds

Low-risk cancers that do not have any symptoms and presumably will not cause problems in the future are responsible for the rapid increase in the number of new cases of thyroid cancer diagnosed over the past decade, according to a Mayo Clinic study published in the journal Thyroid. According to the study authors, nearly one-third of these recent cases were diagnosed when clinicians used high-tech imaging even when no symptoms of thyroid disease were present.

"We are spotting more cancers, but they are cancers that are not likely to cause harm," says the study's lead author, Juan Brito Campana, M.B.B.S., an assistant professor of medicine at Mayo Clinic. "Their treatment, however, is likely to cause harm, as most thyroid cancers are treated by surgically removing all or part of the thyroid gland. This is a risky procedure that can damage a patient's vocal cords or leave them with lifelong calcium deficiencies." Dr. Brito says harm is not limited to physical suffering. "Treatment can cause financial hardship for patients and their families and for society as a whole, as millions of dollars are spent for unnecessary and problematic surgeries," he says....At the same time, the incidence of thyroid cancer is increasing more rapidly than that of any other cancer and is on track to become the third most common cancer in women.

In this study, Dr. Brito and his colleagues drew on data from the Rochester Epidemiology Project. They analyzed the records of 566 men and women who were diagnosed with thyroid cancer in Olmsted County, Minnesota, between 1935 and 2012. Specifically, they examined the number of new cases of thyroid cancer, the deaths due to the disease, and the method of diagnosis.

Researchers found that the number of new cases of thyroid cancer doubled in recent years -- from 7.1 per 100,000 people from 1990 to 1999 to 13.7 per 100,000 people from 2000 to 2012. Over the same period, the number of new patients with thyroid cancer presenting with symptoms of thyroid cancer remained the same. In contrast, the number of new cases of silent thyroid cancer -- the kind where patients have no symptoms -- almost quadrupled. The proportion of patients with thyroid cancer who die of the disease has not changed since 1935.

The study found that the most frequent reasons for identifying silent thyroid cancer were review of thyroid tissue removed for benign conditions (14 percent); incidental discovery during an imaging test (19 percent); and investigations of patients with symptoms or palpable nodules that were clearly not associated with thyroid cancer, but triggered the use of imaging tests of the neck (27 percent)."We are facing an epidemic of diagnosis in thyroid cancer," says Dr. Brito. 

Researchers say one approach to curtail the detection of these lesions would be to limit the use of certain imaging technologies. Another tactic would be to engage patients in deliberating their treatment options. In many cases, active surveillance may be preferred over surgery by patients with small, relatively benign cancers that could take decades to grow to any appreciable size or cause life-threatening problems. Dr. Brito thinks something as simple as not using the word "cancer" to refer to these small and silent thyroid lesions could reduce the number of unnecessary treatments for patients with a more favorable prognosis. Rather than calling these lesions thyroid cancer, he would recommend a less emotionally charged term, such as papillary lesions of indolent course.

 Credit: Mayo Foundation for Medical Education and Research

The issue of overdiagnosis and overtreatment has recently been in the news, especially when discussing breast cancer, prostate cancer, and thyroid cancer. Meaning too much unnecessary treatment with harms, when the best approach would have been to do nothing, as studies have suggested or actually shown. Now here is an article in Medscape suggesting that rather than be quick to operate or treat, the best approach for nearly 70% of prostate cancers may be just "watching".

The U.S. Preventive Task Force, which analyzes the value of screening tests, in May 2012 recommended AGAINST routine prostate-specific antigen (PSA)-based screening for prostate cancer for all age groups. According to them, studies do not show that benefits of routine screening of asymptomatic prostate cancer and the resulting treatment outweigh the harms of treatment (e.g., surgical complications including death from surgery, erectile dysfunction, urinary incontinence, bowel dysfunction, and bladder dysfunction), or that prostate cancer treatment even reduces mortality (deaths). They point out that: "There is convincing evidence that PSA-based screening programs result in the detection of many cases of asymptomatic prostate cancer. There is also convincing evidence that a substantial percentage of men who have asymptomatic cancer detected by PSA screening have a tumor that either will not progress or will progress so slowly that it would have remained asymptomatic for the man's lifetime. The terms "overdiagnosis" or "pseudo-disease" are used to describe both situations." (NOTE: others have argued against this recommendation)

When reading the full Medscape article, it was pointed out that in the study being discussed, one person who was offered active surveillance but declined and was treated with an immediate radical prostatectomy, still died of metastatic prostate cancer. This was an example of a case where when the disease is truly aggressive, it may have spread "like a bird" throughout the body (in Dr. H. Gilbert Welch's terms in his books Overdiagnosed and Less Medicine, More Health) from the very beginning, and may be unstoppable no matter what is done. I have also noticed reading other prostate cancer studies that a certain percentage of prostate cancers regress from the point of diagnosis (the PSA test and biopsy). In other words, researchers are finding that cancer can have different paths: regresses, stays the same, grows slowly (and can be treated when symptoms appear), or grows very quickly and is so aggressive and unstoppable that it goes through the body "like a bird". And we don't know which will be the aggressive ones when we first find them, thus the controversies over what to do: screen or not?, and treat or not? From Medscape:

Nearly 70% of US Prostate Cancers Could Be Watched

More than two-thirds (68%) of all prostate cancers in the United States qualify for active surveillance, according to a study published in the September issue of the Journal of Urology. And if a more stringent definition of surveillance eligibility is used, 44% of cases would be candidates for monitoring instead of immediate treatment, say senior author Ian M. Thompson III, MD, from the University of Texas Health Science Center at San Antonio, and colleagues. These "target" figures are especially credible because they come from a population-based study funded by the National Cancer Institute, and the 3828 participants from Texas undergo regular prostate-specific antigen (PSA) testing.

Of the 320 men in the cohort who developed prostate cancer from 2000 to 2012, 281 had data that were sufficient to allow scoring on very detailed surveillance scorecard.Disease characteristics, such as a high Gleason score, rendered 131 of the 320 men ineligible for active surveillance. But 123 of the men (44%) met a conservative set of criteria and were eligible for surveillance.These "lowest-risk" patients had a PSA density below 15%, fewer than three cores involved with cancer, a Gleason score of 6 or less, and cancer involving 50% of biopsy volume or less. Another 64 men (24%) were eligible when a more expansive set of criteria was used. These "higher-risk" men had fewer than five cores with Gleason 3 + 3 cancer and only one core of Gleason 3 + 4 cancer with up to 15% of the core involved with the Gleason 3 + 4 disease.

When the two groups were combined, 187 patients (68%) were eligible for active surveillance. Predictably, the number of men who actually chose active surveillance was much lower. From 2000 to 2007, 11% of the men diagnosed with prostate cancer opted for surveillance. From 2007 to 2012, 35% of the men opted for surveillance.

Active surveillance should be offered to "an expanded population of well-informed men who may value preserving function above a small risk of disease progression," write Marc Dall'Era, MD, from the University of California, Davis, and Peter Carroll, MD, from the University of California, San Francisco, in an accompanying editorialIn other words, the approach is not just for the lowest-risk cases, they opine.They explain that "the risks of adverse disease-specific outcomes will likely be higher with the inclusion of men with more intermediate-risk features." However, the "absolute risk may still be low," they write.

Perhaps even more important, the study authors observe, is that if the well-documented phenomenon of upgrading or upstaging "truly translated to subsequent consequential outcomes," then "far greater" rates of disease progression, metastases, and death would have been reported in other series of patients. And that has not happened.

 The pair also point to the current study as proof that active surveillance is a reasonable approach, not just for "very-low-risk" disease, but for low- and intermediate-risk prostate cancer, too.

Notably, two of the 320 patients in the Texas cohort either experienced metastatic disease or died of prostate cancer.One of these patients met the expanded criteria and was eligible for active surveillance. "While this could argue against active surveillance, it is notable that this patient underwent radical prostatectomy immediately following diagnosis," the authors explain. The other patient, who was ineligible for surveillance under either definition, was treated definitively but experienced disease progression.     

The prostate gland is located beneath a man's bladder.    Credit: Alila Medical Media | Shutterstock