FDA Approves Noninvasive Stool DNA Test for Colorectal Cancer Screening

Developers anticipate launching the Cologuard Plus test with Medicare coverage and supplementary guidelines in 2025.

The FDA has approved a next-generation multitarget stool DNA test, the Cologuard® Plus test, as a screening tool for individuals who are 45 years or older and are at average risk of having colorectal cancer (CRC), according to a press release from the developer, Exact Sciences Corp.¹

Developers designed the Cologuard Plus test to employ new biomarkers and enhanced laboratory processes while making use of improved sample stability components, thereby giving patients a larger window to return their sample to the lab. Developers anticipate launching the Cologuard Plus test with Medicare coverage and supplementary guidelines in 2025.

Supporting findings for the approval came from the BLUE-C study (NCT04144738), in which investigators assessed the use of the Cologuard Plus test compared with an independent fecal immunochemical test (FIT) for more than 20,000 adults who were 40 years or older and at risk of having CRC. Data from the BLUE-C study were published in The New England Journal of Medicine.²

Use of the multitarget stool DNA test yielded a sensitivity rate of 93.9% (95% CI, 87.1%-97.7%) for CRC screening. Additionally, the test demonstrated a specificity rate of 90.6% (95% CI, 90.1%-91.0%) for detecting advanced neoplasia and a sensitivity rate of 43.4% (95% CI, 41.3%-45.6%) for advanced precancerous lesions. Investigators also reported that the test produced a specificity rate of 92.7% (95% CI, 92.2%-93.1%) among individuals with nonneoplastic findings or a negative colonoscopy result.

Compared with FIT, use of the stool DNA test was associated with improved sensitivity when screening for CRC (P <.001) and advanced precancerous lesions (P <.001). With a fixed specificity rate of 90.6% for the stool DNA test, FIT demonstrated a sensitivity of 75.5% (95% CI, 65.8%-83.6%) and 31.8% (95% CI, 29.8%-33.8%) in the detection of CRC and advanced precancerous lesions, respectively, which were lower than those achieved with the stool DNA test.

“To meaningfully improve outcomes in [CRC], we must catch cancer early—when it is most treatable—and find advanced precancers, which can prevent cases of this cancer,” lead study author Thomas F. Imperiale, MD, professor of medicine at the Indiana University School of Medicine, research scientist at the Regenstrief Institute, stated in the press release.¹ “The high [CRC] sensitivity and specificity of the Cologuard Plus test gives me confidence in the test’s ability to do just that while simultaneously maintaining a low risk of false positives. This makes the Cologuard Plus test a strong option for first-line screening of [patients who are] average risk.”

Investigators of the BLUE-C study assessed individuals who were 40 years or older, asymptomatic, and scheduled to receive a colonoscopy. Prior to colonoscopy, investigators collected stool specimens for the next-generation multitarget DNA test and FIT, which were inspected for acceptability. All samples underwent central evaluation by 1 or more independent pathologists.

The trial’s primary end points were the sensitivity of the multitarget stool DNA test in detecting CRC and its specificity in detecting advanced neoplasia. Secondary end points included sensitivity for advanced precancerous lesions, specificity for nonneoplastic findings or negative colonoscopy, and sensitivity for CRC and advanced precancerous lesions with the stool DNA test vs commercial FIT.

“Cologuard Plus sets a new performance standard in noninvasive [CRC] screening for patients. Cologuard Plus detects cancers and precancerous polyps with even greater sensitivity than Cologuard while reducing false positives by more than 30%. This breakthrough comes at a critical time, when 60 million Americans are not up to date with screening,” Kevin Conroy, chairman and chief executive officer at Exact Sciences, concluded.¹

References

1. FDA approves Exact Sciences’ Cologuard Plus test, setting a new benchmark in non-invasive colorectal cancer screening. News release. Exact Sciences Corp. October 4, 2024. Accessed October 4, 2024. https://tinyurl.com/568rp6ux
2. Imperiale TF, Porter K, Zella J, et al. Next-generation multitarget stool DNA test for colorectal cancer screening. N Engl J Med. 2024;390(11):984-993. doi:10.1056/NEJMoa2310336