key papersKey paper

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

In more than 27,000 average-risk adults who then had a colonoscopy, Freenome's blood test picked up 79 percent of bowel cancers with few false alarms, but found only one in eight advanced precancerous polyps.

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.

Observational studyChanged practice27,010 participants

Authors

Shaukat A, Burke CA, Chan AT, et al.

Published

JAMA, 2025

Full text

doi:10.1001/jama.2025.7515 PubMed 40455622

Findings

Sensitivity for colorectal cancer 79.2 percent (57 of 72; 95 percent CI 68.4 to 86.9).
Specificity for advanced colorectal neoplasia 91.5 percent; negative predictive value 90.8 percent; positive predictive value 15.5 percent.
Sensitivity for advanced precancerous lesions 12.5 percent, below the prespecified acceptance criterion.

What it means

This is the validation study behind the July 2026 FDA approval of SimpleScreen CRC. For someone who will not take a stool test or colonoscopy it offers a real option for catching cancer, but because it misses most advanced polyps it prevents fewer cancers than the established tests, and a positive result still needs a colonoscopy.

Caveats

Cross-sectional accuracy study; it does not measure whether screening with the test reduces colorectal cancer deaths.
The evaluable cohort of 27,010 is a subset of the 48,995 enrolled on the registry.
Funded by Freenome; several authors are employees or consultants.