“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…)