Overdiagnosis and Pseudodisease

What is overdiagnosis? 

Overdiagnosis is the diagnosis of “disease” that will never cause symptoms or death during a patient’s lifetime. It’s a side effect of our relentless desire to find disease early through annual checkups and screening.  Overdiagnosis occurs when a disease is diagnosed correctly, but the diagnosis is irrelevant. A correct diagnosis may be irrelevant because treatment for the disease is not available, not needed, or not wanted.

What’s the problem with wanting to know if there’s a cancer or disease lurking in our bodies?

The problem is, we all harbor abnormalities. Today with our technology we have all sorts of tests that are increasingly able to find our potential health problems, yet most of these abnormalities will not go on to cause disease.

Jennifer Durgin wrote: “Due to the sophisticated scanning technology, like computed tomography (CT) and magnetic resonance imaging (MRI), we’re able see ourselves at a level of detail that has never before been possible. Dartmouth radiologist William Black, M.D, said.”Because we’re now able to see every millimeter of the body, we of course find a lot more abnormalities in the body than we ever knew existed. Oh, there is this ton of tumors out there and other diseases, so disease must really be increasing in frequency.'” But is it?”

But because doctors don’t know which abnormality will and which will not develop into full blown disease, they tend to treat everybody. That means doctors are treating those who cannot benefit because there’s nothing to fix, and these people can be harmed.

What’s the harm?

Overdiagnosed patients cannot benefit from the detection and treatment of their “cancer”, because the nature of the cancer was never destined to cause symptoms or death in the first place. So patients can only be harmed instead due to the following.

  • Overdiagnosis triggers overtreatment or unnecessary treatments.  All medical interventions have side effects. This is particularly true of cancer treatments. Surgery, radiation and chemotherapy all pose varying morbidity and mortality risks.
  • Psychological effects – just being told that you have “cancer” makes your world turns upside down. Unknown to both doctors and patients, this so-called “cancer” may not be harmful after all.
  • Unnecessary expenditure due to the cost of treatment from which the patient cannot benefit, because the disease posed no threat.

Who benefits from overdiagnosis?

 A lot of people: drug companies, device manufacturers, imaging centers, hospitals and of course the doctors. The easiest way to make money is not to make a better drug or build a better device—it’s to expand the market for existing drugs and devices by expanding the indication to include more patients. Similarly, for hospitals, the easiest way to make money isn’t to deliver better care; it’s to recruit new patients—and to make patients to come for regular checkups.

Early detection of cancer – the cause of overdiagnosis

Overdiagnosis is the side effect of the systematic evaluation of asymptomatic patients to detect early forms of cancer, as in the widely promoted “Early Detection” or “Screening” for cancers (in breast, prostate, etc.). This procedure may detect abnormalities that meet the pathologic definition of cancer as seen under the microscope and interpreted by the pathologists. But these abnormalities will not progress to cause symptoms or death during a patient’s lifetime.

A patient once said this to me, A cancer is a cancer. And like it or not it must be taken out. There is this long-standing assumption that all cancers when found early will inevitably progress to become full blown cancer. This assumption does not hold true all the times. Some pre-clinical cancers will not progress to cause problems for patients.

It has long been known that some people have cancers with short pre-clinical phases (fast growing, aggressive cancers), while others have cancers with long pre-clinical phases (slow growing cancers). Pre-clinical phase is defined as the time period that begins with the onset of an abnormal cell and ends when the patient notices symptoms from the cancer.

The figure below depicts the heterogeneity of cancer progression using 4 arrows to represent 4 categories of cancer progression.

Source: Gilbert Welch, Should I Be Tested for Cancer? pg.55

  1. The arrow labeled “Fast” represents a fast growing cancer, one that quickly leads to symptoms and to death. These are the worst forms of cancer.
  2. The arrow labeled “Slow” represents a slow growing cancer, one that leads to symptoms and death but only after many years.
  3. The arrow labeled “Very Slow” represents a cancer that never causes problems because it is growing very slowly. If a cancer grows slowly enough, then patients will die of some other cause before the cancer gets big enough to produce symptoms.
  4. The arrow labeled “Non-progressive” represents a cancer that never causes problems because it is not growing at all. In other words, they are cellular abnormalities. They meet the pathologic definition of cancer but never grow to cause problem simply because it stops growing or perhaps even shrinks. You may have thought that all cancers progress. That is not the case.

Some cancers outgrow their blood supply and are starved, others are recognized by the host’s immune system and are successfully contained, and some are not that aggressive in the first place. They don’t need to be treated and are harmless.

From the above it is clear that all cancers are not created equal. Some grow rapidly and invade other tissue, others grow slowly and remain noninvasive, and some don’t grow at all or may even recede. So many of the cancers that doctors are finding and treating today are what’s called “pseudodisease”—tumors that will never cause harm, let alone kill you.

Pseudodisease

Nonprogressive cancers and very slow growing cancers are collectively referred as pseudodisease (meaning “false disease’). Pseudodisease is, therefore, a type of cancer that need not be treated.  Steven H Woolf, MD, MPH, writing in the British Medical Journal, 18 November 2003, said, “Pseudodisease is the portion of the iceberg below the waterline. Modern medicine is too ignorant to know for sure which of the submerged parts are worth detecting. Doctors of the future will know better. Until then, caution is warranted as we probe beneath the water. (http://www.bmj.com/content/327/7418/E206.full)

Dr. William Black said, “It should be pointed out that pseudodisease is almost impossible to document in a living individual. When pseudodisease is treated, as it almost always is, long-term survival is attributed to the treatment and is labeled a cure. In the rare instances when it is not treated because of old age or other contraindication, pseudodisease cannot be confirmed as such while the patient is still alive because, by definition, it must remain asymptomatic until the patient dies of other causes. These problems with documentation probably explain why pseudodisease has received relatively little attention.”

The medical community doesn’t know enough about some cancers to predict how they will behave over time. So it’s safer, they reason, to label a questionable abnormality as “cancer” and to treat it, than it is to risk its growing out of control. Only after an untreated person dies from other causes can a cancer be declared pseudodisease. Only then is it clear that treatment of the cancer would have provided no benefit, only potential harm.

Examples of cancers that don’t progress 

1. Neuroblastma:  This is a rare form of cancer that typically affects young children. This cancer generally starts near the kidney. It  can grow to as large as a grapefruit, can invade major blood vessels and can metastatasize to major organs like the liver. They can kill children. In Japan, parents of 11 six-month-old infants declined surgery or chemotherapy for their infants. Instead they opted for watchful waiting.  This decision turned out to be a blessing. The cancers in these 11 children began to grow smaller and eventually regress.

2.  Kidney cancer: Radiologists at New York University Medical Center reported the growth of 40 small kidney tumours (less than 3.5 cm in diameter). The three fastest-growing tumours increased  in diameter by about 1 cm per year. The remaining 37 grew considerably slower – less than 0.6 cm per year. Some did not grow at all. Twenty-six of the tumours grew large enough that they were ultimately removed, but fourteen never grew large enough for the doctors to recommend surgery. More important , no one developed metastases or any symptoms from their cancer and no one died of renal cell carcinoma.

3.  Breast cancer: The incidence of ductal carcinoma in situ (DCIS) rose dramatically in the US after mammography screening became widespread. DCIS now accounts for 1 out of 5 newly diagnosed breast cancers.

More than one half million women have been diagnosed with DCIS in the past 20 years in the US. Virtually all of them were treated with surgery, radiation and chemotherapy as if they had invasive breast cancer.  DCIS is actually quite prevalent in the population and is present in 40% of the findings of autopsies conducted in middle-age women who die of other causes.

Most DCIS is psedodisease. Although rarely done, watchful waiting may be a reasonable strategy for many women with DCIS.

4. Prostate cancer: Autopsy studies had shown that elderly men who died of other causes often had histologic evidence of prostate cancer, latent disease that was clinically silent while these men were alive. Introduction of a screening test (prostate-specific antigen – PSA) in the late 1980s brought an “epidemic” of prostate cancer to the United States in the early 1990s.

“The most compelling evidence that pseudodisease is a real problem comes from the experience with prostate cancer. Prostate cancer is the second-leading cause of cancer-related death in American men, and over the last 30 years, more and more of it has been found. In 1975, about 100,000 new cases were diagnosed; in 2003, about 220,000. At first glance, one might conclude that prostate cancer is on the rise. However, if a cancer is “really increasing,” you’d expect death rates to rise. And that hasn’t happened with prostate cancer. The death rate has remained more or less constant, hovering around 30,000 deaths per year in the U.S.

5. Lung cancer:  Swensen describes the pseudodisease that emerges when computed tomography (CT scan) is used to screen for lung cancer. It detected 56 lung cancers over 4 years at the Mayo Clinic, but also a much larger number of uncalcified chest nodules, 98% of which were benign. He notes that wedge resection carries a 4% mortality rate, raising the prospect of patients’ dying on the operating table in the pursuit of pseudodisease.

Twenty years ago, Yale researchers examined the autopsy reports of patients (generally over age 60) who died at Yale-New Haven Hospital and who were not known to have lung cancer during life. The rate of surprise cases of lung cancer in these autopsies was 10 times the rate of lung cancer diagnosed in the general population. What does this mean?

If pathologists found very few kung cancers in patients not known to have cancer in life, doctors could expect that most small lung cancers they do find will progress to be the type of lung cancer we all fear.

However, if pathologists find a high incidence of lung cancers in patients not known to have cancer in life, doctors need to recognize that many small lung cancers detected by CT scan may be pseudodisease.

6. Thyroid cancer:  Pathologists in Finland examined the thyroid gland in 101 autopsies. Over a third of the autopsied patients had thyroid cancers! But thyroid cancer is rare in Finland as well as in the United States. However, many of the cancers they found were small, some as small as 0.2 mm in diameter. The researchers concluded that virtually everybody would have some evidence of thyroid cancer if examined carefully enough.  Put another way, we might say that the smallest forms of thyroid cancer are so common that they should be regarded as normal.

Summary

Let me end this discussion with the following statements by Dr. Gilbert Welch:

  1. Not all cancers should be treated. Some small cellular abnormalities that are called “cancer” will not progress to cause symptoms or death. Others will progress so slowly that people will die of something else before they ever have symptoms of cancer.
  2. It is practically impossible to know for sure whether an individual cancer is, in fact, pseudodisease.
  3. There is a bottomless reservoir of cancer in the general population – the harder you look for it, the more you find but this pseudodisease will never harm the individual anyway.
  4. As  diagnostic methods and equipments become more sophisticated doctors are beginning to find smaller and smaller tumours in such organs as the thyroid gland, kidney, lung and breast.
  5. The fact that pseudodisease exists suggests that the correct approach to cancer is not always treatment. Instead, watchful waiting may be a reasonable strategy.

Points for You to Ponder On

  1. Given that there is such a thing as pseudodisease, do you really need to go “hunting” for cancer every  year  in the forms of mammogram, PSA test, colonoscopy, etc, etc?
  2. The person who determines whether you have cancer or not is really not your doctor but the pathologist. He studies a bit of your tissues under a microscope and decides if you have cancer or not. Do you think he is 100 percent right all the time? Can he be 100 percent sure that the abnormal cells that he observe under the microscope  would grow in you and become a full blown, dangerous cancer?
  3. Given that all cancers are not created equal, is the standard “all-size-fits-all”  recipe of surgery, chemotherapy, radiotherapy (and taking hormones in breast cancer) the only correct solution for every cancer?

Read more:

  1. Gilbert Welch, M.D., M.P.H. Should I Be Tested for Cancer? Maybe not and here’s why, University of California Press.
  2.  Lisa Chedekel, http://www.bu.edu/today/2011/medical-overdiagnosis-bad-for-you-good-for-business/
  3. http://en.wikipedia.org/wiki/Overdiagnosis
  4. William Balck, http://jnci.oxfordjournals.org/content/92/16/1280.full.pdf
  5. Jennifer Durgin, http://dartmed.dartmouth.edu/summer05/print/hunting.php

 

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