Blood Test Achieves Improved Detection of Advanced Precancerous Colorectal Lesions

Colorectal cancer is the second-leading cause of cancer-related death in the United States, yet screening uptake remains suboptimal. More than 50 million eligible adults are not up to date with recommended screening, and blood-based options could help reach individuals who otherwise remain unscreened. A newly reported clinical validation of an updated blood-based screening test now demonstrates improved detection of advanced precancerous lesions while meeting all primary and secondary endpoints.

Freenome’s (Brisbane, CA, USA) updated SimpleScreen CRC blood-based colorectal cancer screening test met all primary and secondary endpoints in a pivotal clinical validation evaluating assay and algorithm enhancements over the first-generation test. Adjusted to the age and sex distribution of the U.S. Census, the analysis showed 90% specificity among individuals with no findings on colonoscopy. The test achieved 80.4% sensitivity for colorectal cancer (CRC) and 18.2% sensitivity for advanced precancerous lesions (APLs), including 41.9% sensitivity for APLs with high-grade dysplasia (HGD).

The SimpleScreen CRC platform uses a multiomics approach that analyzes multiple blood-based signals and applies artificial intelligence and machine learning to detect cancer-associated patterns. The updated version reflects improvements to both the underlying assay and the classification algorithm, with the goal of detecting cancer when it is most treatable.

The clinical validation incorporated blinded, previously unevaluated samples from participants enrolled in PREEMPT CRC, a prospective registrational study, along with previously tested samples. PREEMPT CRC was conducted at more than 200 sites and enrolled 48,995 asymptomatic, average-risk adults aged 45–85 who were scheduled for screening colonoscopy. The current analysis included more than 85 individuals with CRC, 1,500 with APLs, and 150 with APLs with HGD.

Stage-specific performance included detection of 52% of stage I cancers overall, comprising 39.9% for stage I (T1) and 81.2% for stage I (T2), as well as 100% of stage II, 97.3% of stage III, and 100% of stage IV cases. The reported APL and HGD sensitivities were described as the highest to date for any noninvasive blood-based screening test evaluated in a prospective registrational pivotal clinical study. Modeling projected that, per 100,000 individuals screened, the updated test performance would yield 1,582 additional life-years gained (7.7%), 426 fewer CRC cases (9.5%), and 143 fewer CRC deaths (9.5%) compared with the first-generation test.

A Premarket Approval application for the first-generation SimpleScreen CRC test was submitted to the U.S. Food and Drug Administration (FDA) in August 2025, with review expected to conclude in mid-2026. A supplemental application is planned for the next-generation version. Upon approval, the test is expected to be exclusively commercialized and made available by Abbott.

“The sensitivity for APL and APL with HGD for the updated SimpleScreen CRC test is a marked improvement and gets us closer to matching the performance of certain stool-based CRC screening tests, with potentially higher adherence,” said Aasma Shaukat, M.D., M.P.H., professor of medicine at NYU Grossman School of Medicine and a co-lead principal investigator on the PREEMPT CRC study.

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