New Blood-Based Colorectal Cancer Screening Test Results

Colorectal

Douglas K. Rex, MD, MASGE reviewing Chung DC, et al. N Eng J Med 2024 Mar 14.

Effective blood-based screening for colorectal cancer (CRC) remains an important goal because adherence to CRC screening is suboptimal, and there is evidence that a notable fraction of patients would prefer blood-based screening to invasive imaging and stool-based testing. The first commercially available blood-based test, which was based on septin 9, had inadequate sensitivity and specificity and was subsequently withdrawn.

A new study describes the performance of a new blood test based on cell-free DNA (cfDNA) in a screening colonoscopy cohort of 7861 patients aged 45 to 84 years, in whom 65 CRCs were detected, including 48 stage I to III cancers. Key findings were:

Overall CRC sensitivity of the cfDNA test was 83.1%, and sensitivity for stage I to III cancers was 87.5%. The test detected 11 of 17 (65%) stage I cancers, 14 of 14 (100%) stage II cancers, and 17 of 17 (100%) stage III cancers. The estimated positive predictive value (PPV) for CRC screening was 3.2%.
Sensitivity for advanced precancerous lesions (adenoma or sessile serrated lesion ≥10 mm, villous features, or high-grade dysplasia) was 13.2%, with an estimated screening PPV of 12.9%.
The specificity for the group without any advanced neoplasia was 89.6%.

Comment:

These performance features meet prespecified criteria from the Centers for Medicare and Medicaid Services for coverage of a test that has received U.S. Food and Drug Administration approval for CRC screening. These performance features are improvements in both sensitivity and specificity for CRC compared with those of the septin 9 test.

Big picture: Blood-based CRC screening has the potential to improve adherence. However, with a 13.2% sensitivity for advanced precancerous lesions, which is barely higher than the false positive rate of 10.4%, the test has extremely poor sensitivity for advanced precancerous lesion detection. It is very unlikely this test will be cost-effective relative to current tests. This test moves the CRC screening concept away from prevention to detection only. Any availability of this test increases the importance of clarifying and educating clinicians on the importance of sequential offers of screening tests. In particular, the availability of the cfDNA test should be accompanied by recommendations for colonoscopy and the currently available fecal tests first, reserving the cfDNA test for patients who decline colonoscopy and fecal testing and understand the limitations of the cfDNA test.

Douglas K. Rex, MD, MASGE

Bio and Disclosures

Citation(s):

Chung DC, Gray DM 2nd, Singh H, et al. A cell-free DNA blood-based test for colorectal cancer screening. N Eng J Med 2024;390:973-983. (https://doi.org/10.1056/nejmoa2304714)