Prenatal testing, cancer risk and the overdiagnosis dilemma

Abstract

In March, US company Sequenom revealed that its MaterniT21 non-invasive prenatal test (NIPT) has detected potential cancer in some pregnant women (see BioNews 793). As well as receiving information about their fetus, around 40 of the 400,000 or so women who have had this test have been informed that they may have cancer. One example of this was Dr Eunice Lee, who had investigations following an abnormal NIPT result that identified a 7cm colorectal tumour, which was then surgically removed. This is a good thing, right? Women in the prime of their lives receiving information that may catch a cancer early. But, we suggest, it is not this simple. So-called liquid biopsies lead to ethical issues that go beyond the matter of using a test for one thing and finding out about something else. They are also a prime example of the problem of overdiagnosis. Before diving into this particular biopsy pool, we need to think carefully about what might be under the surface. Overdiagnosis is hard to define, but, loosely, an overdiagnosis is a correct diagnosis that doesn’t benefit a patient. It occurs when a test finds something that, if left alone, would regress, or never become symptomatic. Although in practical terms the line between false positives and overdiagnosis can be blurry, the conceptual distinction is this: an overdiagnosis is a correct diagnosis that doesn’t benefit, while a false positive is an incorrect test result: a finding that is not actually true. Both can lead to harm, such as having unnecessary medical interventions. They also consume valuable and often scarce health resources. We know neither the extent of overdiagnosis nor the false-positive rate for suspected cancer detection following NIPT. The latter will be measurable soon enough, but pinning down rates of overdiagnosis will be difficult.