NASHVILLE, Tenn. — Updates to an FDA-approved colorectal cancer (CRC) blood test increased the detection of advanced precancerous lesions (APLs), a new study showed.

“The updated test has improved performance, better detection of advanced precancerous lesions, resulting in larger projected reductions in CRC incidence and mortality at the population level,” said first author Aasma Shaukat, MD, MPH, of the NYU Grossman School of Medicine in New York City.

Although colonoscopy and stool-based testing continue to be recommended as first-line screening in American Cancer Society guidelines, “for patients who are unwilling or just will not proceed with screening, we can consider offering them a blood test,” said Shaukat, who presented the findings at the American College of Gastroenterology (ACG) 2026 Annual Scientific Meeting.

“It’s still better than no screening,” she noted.

SimpleScreen CRC Blood-Based Test

Blood-based CRC screening tests, which evaluate cell-free DNA changes in the blood, are recommended mainly as a secondary screening option due to their lower accuracy compared with fecal immunochemical testing (FIT) and colonoscopy; however, as technology advances, ongoing updates continue to improve results.

In her talk, Shaukat reported on results observed following updates to the assay and algorithms of the SimpleScreen CRC test, which was introduced in 2025 and subsequently received FDA approval.

The analysis included 9131 samples from an average-risk population, including 26 previously untested CRC samples and 1142 APL samples from the PREEMPT CRC trial, the prospective, multicenter validation study for SimpleScreen of patients undergoing screening colonoscopy.

Additional previously tested samples were added to increase the statistical power of CRC (n = 70) and APL samples (n = 517, randomly selected, and n = 70 with high-grade dysplasia [HGD]), and together, those samples were matched with nearly 7342 tested and untested samples without advanced colorectal neoplasia. The results were adjusted for age and weight distribution.

With a 90% specificity, the updated test showed a sensitivity of 80.4% for the detection of CRC, including a 52.1% sensitivity for stage I, 100% for stage II, 97.3% for stage III, and 100% for stage IV.

While the sensitivity generally was unchanged across cancer stages with the updates and declined for stage I (from a pre-update sensitivity of 63.5%), the notable improvement was in stage III CRC, which increased by 16.8%.

In the detection of APL, the overall sensitivity with the updates was 18.2% compared with 13.7% in the test’s first version. For the detection of APL with HGD, the sensitivity was 41.9% compared with a pre-update sensitivity of 30.5%.

“Overall, the updated version of the [SimpleScreen] CRC blood test showed significant improvement in APL sensitivity,” Shaukat said.

Importantly, “compared with the previous test, this improved performance would result in nearly 10% fewer CRC cases and deaths, and nearly 8% more life-years gained,” she pointed out.

From Cancer ‘Detection’ to ‘Prevention’?

Not only do the findings show the test to be better than no screening, “they are quite significant because they are the first to suggest a blood-based test can actually detect a precancerous lesion, rather than only an invasive cancer,” said Michael Dougherty, MD, attending gastroenterologist at University of North Carolina Rex Digestive Healthcare in Chapel Hill, in comments on the study to Medscape Medical News.

“This potentially moves this test slightly over into the ‘cancer prevention’ space instead of merely a ‘cancer detection’ one,” he explained.

Dougherty noted that the previous low sensitivity in detection of APLs of about 13% with SimpleScreen and other blood-based tests made sense because precancerous polyps, by definition, “don’t invade to the depth of the submucosa where all the blood and lymphatic vessels are, so for a marker from a merely precancerous polyp to make it to the general [blood] circulation, in a detectable concentration, should be very difficult in principle.”

“But to reach 18% seems like the test is really detecting something, somehow,” he said.

Furthermore, Dougherty said the “impressive” sensitivity for HGD was “particularly striking.”

“This is encouraging because it also makes intuitive sense and is important for patient outcomes.”

Dougherty noted that overall, blood-based CRC tests still have pros and cons to be weighed.

“If they help to get more people screened overall, they are a win and will save some lives,” he said.

“But if some individuals who would have otherwise opted for a superior test [such as FIT or colonoscopy] opt for SimpleScreen out of convenience, that is detrimental to population cancer prevention.”

Shaukat reported having consulted for Freenome Holdings, Inc., the manufacturer of SimpleScreen. Dougherty reported having no disclosures to report.