CLINICAL QUESTION

How accurate is a DNA-based blood test for detecting advanced adenoma and colorectal cancer (CRC) in asymptomatic patients?

BOTTOM LINE

The cell-free DNA-based blood test has good sensitivity for detecting stage 2 to stage 4 CRC in asymptomatic patients, and fair sensitivity for stage 1 cancers. However, the sensitivity for advanced adenomas is only 12% and significantly worse than that of a single fecal immunochemical test (FIT), which costs less than $5. There is no evidence regarding the impact of these tests on CRC incidence and mortality when used over a longer duration of screening. Modeling suggests that the use of this test is likely to decrease the uptake of tests known to reduce CRC mortality, with a consequent increase in mortality as a result. Do not order these tests for your patients—instead, make it as easy as possible for them to use FIT or colonoscopy. (Level of Evidence = 2b)

SYNOPSIS

The study evaluated a proposed new screening test for CRC that detects cell-free DNA CpG methylation patterns in a blood sample. The researchers recruited 32,731 asymptomatic participants ages 45 to 85 years who had never had a colonoscopy or had not had one in 9 years. Participants had no specific risk factors for or a history of CRC. Patients had to be willing to undergo colonoscopy within 6 months. Ultimately, 27,010 patients had evaluable results from the blood test and colonoscopy within that time frame. The patients' median age was 57 years, 56% were female, and 27% were non-White. Overall, 0.3% of participants had CRC detected on colonoscopy. The sensitivity of the blood test was 79.2% and the specificity was 81.5%, with a positive likelihood ratio of 9.3 and a negative likelihood ratio of 0.05 compared with colonoscopy. The blood test detected 16 of 28 (57%) stage 1 cancers, 15 of 15 stage 2 cancers, 14 of 17 (82%) stage 3 cancers, and 11 of 11 stage 4 cancers. This is consistent with findings from other similar blood-based tests because they have little chance of detecting a cancer until it invades blood vessels. The test was significantly worse at detecting carcinoma in situ or high-grade dysplasia (32 of 110 [29.1%]) or advanced precancerous lesions (321 of 2,567 [12.5%]). These results are similar to those reported by another study of the blood test Shield by Guardant proposed for CRC screening. The Guardant test has been approved by the US Food and Drug Administration for use every 3 years, with an out-of-pocket cost of $895, but it is covered by Medicare Part B.