Clinical validation of a circulating tumor DNA-based blood test to screen for colorectal cancer (PREEMPT CRC)

Primary publication of PREEMPT CRC (NCT04369053), a prospective, multicentre, cross-sectional observational study at 201 centres across 49 US states and the United Arab Emirates. Asymptomatic adults aged 45 to 85 at average risk of colorectal cancer gave blood before a standard-of-care screening colonoscopy; participants, staff, pathologists and the laboratory were blinded. Primary endpoints were sensitivity for colorectal cancer and specificity, negative predictive value and positive predictive value for advanced colorectal neoplasia; the secondary endpoint was sensitivity for advanced precancerous lesions.

In the evaluable cohort of 27,010 (median age 57.0 years, 55.8 percent women), sensitivity for colorectal cancer was 79.2 percent (57 of 72; 95 percent CI 68.4 to 86.9) and specificity for advanced colorectal neoplasia 91.5 percent (22,306 of 24,371; 91.2 to 91.9). Negative predictive value was 90.8 percent (22,306 of 24,567) and positive predictive value 15.5 percent (378 of 2,443). All primary endpoints met prespecified acceptance criteria. Sensitivity for advanced precancerous lesions was 12.5 percent (321 of 2,567; 11.3 to 13.8), which did not meet its criterion.