How FDA Approval of SimpleScreen CRC Could Expand Colorectal Cancer Screening With Mark Fendrick, MD

The US Food and Drug Administration (FDA) has approved Freenome's SimpleScreen™ CRC, a blood-based screening test for colorectal cancer (CRC) in asymptomatic adults aged 45 years and older who are at average risk for the disease. The approval expands the range of noninvasive CRC screening options available to clinicians and patients and is intended to help improve screening participation among eligible adults.

SimpleScreen CRC detects cell-free DNA (cfDNA) signals associated with colorectal cancer from a blood sample. FDA approval was supported by findings from the PREEMPT CRC study, the largest prospective clinical validation study conducted for a blood-based colorectal cancer screening test.

Mark Fendrick, MD, director of the University of Michigan Center for Value-Based Insurance Design and professor of internal medicine at the University of Michigan, said the availability of a blood-based screening option could help engage patients who have been reluctant to undergo existing CRC screening methods.

"I believe that a blood-based test, which is something that most of my patients undergo a blood draw on a regular basis, will be able to afford some of those individuals who have been reluctant to undergo colorectal cancer screening to actually begin the screening process," Fendrick told HCPLive.

PREEMPT CRC Supports FDA Approval

The FDA approval was based on data from PREEMPT CRC, a prospective clinical validation study that enrolled more than 48,000 asymptomatic adults aged 45-85 years at average risk for colorectal cancer across more than 200 sites. All participants were scheduled to undergo screening colonoscopy, which served as the reference standard for evaluating test performance.

In a prespecified analysis adjusted to reflect the US Census population, SimpleScreen CRC demonstrated 81.1% sensitivity for colorectal cancer and 90.4% specificity for advanced colorectal neoplasia. Sensitivity for advanced precancerous lesions was 13.7% overall and 30.7% for advanced precancerous lesions with high-grade dysplasia.

According to the company, the findings indicate the test correctly detected approximately 8 in 10 colorectal cancers while correctly producing negative results for about 9 in 10 individuals without colorectal cancer or advanced precancerous lesions.

Expanding Screening Options

Colorectal cancer remains the second-leading cause of cancer-related death in the United States despite being highly preventable through routine screening. According to Freenome, an estimated 60 million Americans remain overdue for recommended colorectal cancer screening.

Fendrick said the persistent screening gap reflects more than a lack of awareness, noting clinicians often default to recommending colonoscopy even though many patients prefer less invasive options.

"Our work shows that nine out of 10 clinicians recommend colonoscopy. This same work shows that only a quarter of patients actually would choose colonoscopy when told about the various options that are available to them, which at the time of the study was stool-based testing in addition to colonoscopy. And now we have an additional modality that might be able to tie into those patient preferences that neither like colonoscopy or stool-based testing."

He added that some patients remain interested in screening but are unwilling to undergo colonoscopy or complete stool-based testing.

"There are some patients who would like to be screened for colorectal cancer, but do not want to undergo colonoscopy or deal with their stool, even if it's delivered at home."

For Fendrick, the introduction of blood-based screening is less about replacing existing screening modalities than expanding patient choice and increasing overall screening participation.

"The more options we have and the choices we can make available to our patients will increase the likelihood of screening."

He added that clinicians should continue emphasizing colorectal cancer screening while helping patients choose the option they are most likely to complete.

"I'd really like to abandon the idea of pushing colonoscopy primarily. We should continue to push the importance of colorectal cancer screening in general, and make absolutely sure that we let patients know about the choices that are available to them," he said.

Fendrick emphasized, however, that blood-based screening should be viewed as one component of the screening process rather than a replacement for colonoscopy.

"It's really important for my colleague clinicians, whether they be primary care or in specialty, to make sure that patients know that a stool-based test or a blood-based test is just part of the process,” said Fendrick. “And those who test positive, which is the reason why we have a screening program in the first place, it must be easy, not hard, for them to get a colonoscopy."

SimpleScreen CRC is indicated for adults aged 45 years and older who are at average risk for colorectal cancer. As with other noninvasive CRC screening modalities, a positive result should be followed by diagnostic colonoscopy and the test is not intended to replace diagnostic or surveillance colonoscopy in individuals at increased risk for colorectal cancer.

Editors’ note: Fendrick reports relevant disclosures with AbbVie, Exact Sciences, Johnson & Johnson, Medtronic, Merck and Company, Phathom Pharmaceuticals, and others.

References

1. Shaukat A, Burke CA, Chan AT, et al. Clinical validation of a circulating tumor DNA-based blood test to screen for colorectal cancer. JAMA. 2025;334(1):56-63. doi:10.1001/jama.2025.7515.

2. US Preventive Services Task Force. Screening for colorectal cancer: US Preventive Services Task Force recommendation statement. JAMA. 2021;325(19):1965-1977. doi:10.1001/jama.2021.6238.