On "Liquid biopsies" and other screening tests

Coming to a mall near you! Or at your doctor’s office or via direct mail: the chance to have a “simple blood test” to detect very early cancer and perhaps save your life. What is the truth behind the hype?

The term “liquid biopsy” refers to the screening of a blood sample for traces of abnormal DNA that are felt to be the markers of a variety of cancers. These tests were approved by the FDA in 2020 for a very limited purpose: to detect DNA markers of specific subtypes of known cancers that meant the cancers would respond to specific treatments. The tests were meant to identify specific cancer-related genetic changes which could influence patients’ treatment choices or make them eligible to participate in clinical trials.

While that is a lucrative market, what has Wall Street salivating is a much larger potential: offering such tests to everyone, with the promise of detecting cancer long before it caused symptoms. We have been conditioned to believe that early detection = greater chance for cure, and in some cancers this is valid. If everyone had regular colonoscopies, the death rate from colon cancer would fall. Early detection of lung cancer in smokers using low-dose CT scanning has been shown to reduce lung cancer death and regular mammograms reduce death from breast cancer, though in neither of these latter cancers is the screening test “dramatically” effective.

Before we start recommending very expensive “liquid biopsies” for widescale use, it is critical to look at what they will accomplish rather than what they might.

The idea behind screening tests is to look for disease in apparently well people with the expectation that finding and treating disease before symptoms develop will lead to better health and/or longer life. In the case of colonoscopy, the theory has been validated, but this is not always the case.

Example 1: screening for atrial fibrillation (AF). We know that AF, a heart rhythm disorder that is very common as we age, is a major cause of stroke, and that by putting patients with AF on blood thinners we can reduce their stroke risk by as much as 80%. A recently published study looked at using small monitors implanted under the skin to detect episodes of AF that would never be found routinely. They did detect three times as many episodes of AF – BUT – when they treated these people with blood thinners, there was no real difference in strokes or deaths compared to the group not screened. It appears the brief asymptomatic episodes of AF that were found may not be as serious as AF found in routine practice.

Example 2: screening for thyroid cancer. In 1999, Korea embarked on an aggressive national cancer screening program. While ultrasound screening of the thyroid was not initially included, it quickly became a widely used study. As a result, by 2011 the rate of thyroid cancer diagnosis increased 15-fold over the rate in 1993. Thyroid cancer is now the most common cancer diagnosed in Korea. At the same time, the death rate from thyroid cancer did not budge. Almost all of these cancers are low-grade and small, and we have known for 70 years that low-grade thyroid cancer is very common and rarely kills. Thyroid surgery is not innocuous: patients can have vocal cord paralysis, accidentally have their parathyroid glands damaged and usually need to take thyroid hormone for life. All for a disease that would never have bothered them if not found.

SO: before the FDA approves “liquid biopsies” for screening use and before you consent to having one done, we need evidence that these tests not only detect cancers not otherwise easily found, but that finding these cancers will let you live a longer and/or healthier life. Otherwise, I fear, we are going to see your health made worse by extensive imaging studies looking for this possible hidden cancer and your life put at risk by having surgery that you do not need.

Let’s not put the cart before the horse.

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