Posts Tagged lung cancer

“Liquid biopsies” for cancer screening: Life-saving tests, or overdiagnosis and overtreatment taken to a new level?

Could a blood draw be all you need to diagnose cancer and identify the best treatment for it? Not so fast...

Could a blood draw be all you need to diagnose cancer and identify the best treatment for it? Not so fast…

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…)

Posted in: Basic Science, Cancer, Diagnostic tests & procedures, Public Health

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Recent Developments and Recurring Dilemmas in Cancer Screening: Colon, Lung, Thyroid

Cancer screening - lead time bias small

Screen detection and tumor growth rates. Cancers have different growth rates, which determine their potential to be detected by screening. Tumor A remains microscopic and undetectable by current technology (although more sensitive tests in the future might render it detectable). Tumor B eventually becomes detectable by screening (*), but its growth rate is so slow that it will not cause symptoms during the life of the individual; its detection will result in overdiagnosis. Tumor C is capable of metastasizing, but it grows slowly enough that it can be detected by screening (*); for some, this early detection will result in survival. Tumor D grows very quickly and therefore is usually not detected by screening. This will present as an interval cancer (i.e. detected clinically in the interval between screening examinations) and has a particularly poor prognosis. Note that of the four tumor types, only Tumor C has the potential to benefit from screening. Red dashed lines represent the natural history of a tumor in the absence of detection by screening. (Figure 1 from Gates, 2014).

A new stool DNA test was recently approved by the FDA for colon cancer screening. My first reaction was “Yay! I hope it’s good enough to replace all those unpleasant, expensive screening colonoscopies.” But of course, things are never that simple. I wanted to explain the new test for our readers; but before I could start writing, some other issues in cancer screening barged in and demanded to be included. They exemplify the dilemmas we face with every screening test. We have covered these issues before, but mainly in reference to mammography and prostate (PSA) screening. My article morphed into a CLT sandwich: colon, lung, and thyroid cancer screening.

The current issue of American Family Physician has a great article on cancer screening. It uses lucid graphics to illustrate lead time bias, length time bias, and overdiagnosis bias, as well the effect of varying tumor growth rates on screening success rates, all concepts that have been covered by Dr. Gorski here. Briefly, screening may do more harm than good if:

  1. It detects cancerous cells that never would have developed into invasive cancers or harmed the patient in any way;
  2. Early diagnosis and treatment decrease quality of life without reducing death rates; or
  3. The test falsely indicates cancer in patients who don’t have it or fails to indicate cancer in some who do. (more…)

Posted in: Cancer, Diagnostic tests & procedures

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Hyping Health Risks

Three kids on the same block were diagnosed with leukemia last year. That couldn’t happen just by chance, could it? There MUST be something in the environment that caused it (power lines, the chemical plant down the street, asbestos in their school, iPods, Twinkies?). Quick, let’s measure everything we can think of and compare exposures to other blocks and find an explanation.

That may be the common reaction, and it may seem plausible to the general public, but it’s not good science.

I have just read a book that does a great job of elucidating the pitfalls of epidemiologic studies, the problematic interface between science and emotion-laden public concerns, and the way environmental hazards have been hyped far beyond the evidence. Hyping Health Risks: Environmental Hazards in Daily Life and the Science of Epidemiology by Geoffrey C. Kabat.

He covers the uses, strengths and limitations of epidemiology, discusses the pros and cons of different study designs, and explains how to judge whether an association is causal.

Posted in: Book & movie reviews, Science and the Media

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