Lawrence Herman DMSc, MPA, PA-C
In the March 2020 issue of Annals of Oncology, Liu and colleagues detailed a 'sensitive and specific multi-cancer detection and localization using methylation signatures in cell-free DNA' circulating in blood. This test is now entering clinical practice in a limited number of healthcare systems, and it is important that clinicians understand the risks and limitations associated with the test.
The Galleri test, expected to cost approximately $1000, is intended for patients who are at an increased risk of cancer, such as those 50 years of age or older; it is intended to be used as a complement to existing screening and can detect up to 50 different cancers. It is not yet FDA-approved, but developers expect it to be approved in the second half of 2021. The concept is to detect methylation patterns using cell-free DNA circulating in blood, which can then identify the tissue of origin with a 93% accuracy in samples with cancer-like signals. Liu and colleagues trialed 6689 participants, 2482 of whom had identified cancers. The study results revealed a 99.3% specificity (95% CI), a false-positive rate of 0.7%, and a 54.9% sensitivity in stage I to IV across all cancer types. The higher the stage of the cancer, the greater the sensitivity.
The idea of screening and locating a cancer from a venipuncture is what some might describe as the 'Holy Grail' of preventive screening. However, there remain at least 3 concerns with respect to this test. The first is that the goal of any cancer screening test is to identify the cancer as early as possible, increasing the likelihood of a positive treatment outcome; discovering a late-stage cancer largely obviates the purpose of the screening test. The test has a 43.9% sensitivity in stage I to III cancers, which presents a problem in the fact that a negative result can provide a false sense of security in those with the limited number of cancers detected by the Galleri test.
Secondly, the test does not provide data on other types of cancers not included in its testing. Patients may subsequently decline standard-of-care screenings that could detect an undetected cancer, delaying diagnosis and reducing the likelihood of a positive outcome.
And thirdly, a 0.7% false-positive rate, while small, would trigger not only significant psychological distress on the part of the patient and family, but will result in significant imaging and invasive testing—both short-term and ongoing—to attempt to rule out that false-positive. It is almost impossible to prove a negative. Should this exhaustive additional testing identify no cancer, it is likely that the patient would still experience lasting psychological distress.
Cancer screenings present complex decisions for both the individual patient and population health. These decisions involve sensitivity, specificity, cost, and other factors. This complexity is but one reason why we have recommendations from the United States Preventive Services Taskforce. Currently, I believe that the risks outweigh the benefits for this new test.