Circulating tumor DNA (ctDNA): can it be used as a pan-cancer early detection test?

Abstract

Circulating tumor DNA (ctDNA, DNA shed by cancer cells) is emerging as one of the most transformative cancer biomarkers discovered to-date. Although potentially useful at all the phases of cancer detection and patient management, one of its most exciting possibilities is as a relatively noninvasive pan-cancer screening test. Preliminary findings with ctDNA tests such as Galleri or CancerSEEK suggest that they have high specificity (> 99.0%) for malignancy. Their sensitivity varies depending on the type of cancer and stage of disease but it is generally low in patients with stage I disease. A major advantage of ctDNA over existing screening strategies is the potential ability to detect multiple cancer types in a single test. A limitation of most studies published to-date is that they are predominantly case-control investigations that were carried out in patients with a previous diagnosis of malignancy and that used apparently healthy subjects as controls. Consequently, the reported sensitivities, specificities and positive predictive values might be lower if the tests are used for screening in asymptomatic populations, that is, in the population where these tests are likely be employed. To demonstrate clinical utility in an asymptomatic population, these tests must be shown to reduce cancer mortality without causing excessive overdiagnosis in a large randomized prospective randomized trial. Such trials are currently ongoing for Galleri and CancerSEEK.