Next-Generation Cologuard Plus Test Receives FDA Approval for Colorectal Cancer Screening

On October 4, 2023, the United States Food and Drug Administration (FDA) approved Exact Sciences' test for average-risk adults aged 45 and older: a next-generation multitarget stool DNA (mt-sDNA) test known as Cologuard Plus. Exact Sciences, which worked with Mayo Clinic to develop the new test, says it substantially improves colorectal cancer screening performance.

NOTE: Being at average risk means having no clear risk factors such as family history, genetic predisposition, or personal medical history. In other words, these individuals have the same likelihood of developing cancer as others in the general population. 

The Need for Noninvasive Colorectal Cancer Screening

Although highly treatable when detected early, colorectal cancer ranks second among causes of cancer death in both Western countries and Turkey.

More than two-thirds of people who die from colorectal cancer have not undergone screening for early detection. Early diagnosis is critical: when found at an early stage before spread, the five-year relative survival rate is 91%; if the cancer has metastasized , five-year relative survival is 14%.

Colorectal cancer screening uptake in the United States is only about 59%, well below the recommended 80% target; uptake is also low in Turkey. Most people who should be tested do not complete screening, often because existing options, such as colonoscopy or stool-based tests, are perceived as invasive, unpleasant, or inconvenient.

The persistent screening gap shows that current options do not appeal to millions of people. FDA approval of stool-based Cologuard Plus, together with approval of the blood-based test in 2024, Shield, marks a major step toward closing this gap. These decisions will bring screening to broader populations and usher in a new era of noninvasive colorectal cancer screening. Increased screening and earlier detection could save many lives.

Improved Test Sensitivity and Patient Convenience with Cologuard Plus

Cologuard Plus aims to improve test sensitivity and prevent unnecessary colonoscopies by reducing the likelihood of false-positive results, potentially helping patients avoid unnecessary invasive procedures. Improved sample stability also gives patients more time to return samples to the laboratory, making timely testing more convenient.

Cologuard Plus tests three new DNA methylation markers and hemoglobin in stool to help detect colorectal cancer and precancerous lesions.

FDA Approval Based on BLUE-C

Approval was based on BLUE-C, a study evaluating Cologuard Plus in more than 20 thousand average-risk adults. It compared the next-generation mt-sDNA test with a fecal immunochemical test (FIT) and colonoscopy.

According to BLUE-C, Cologuard Plus had:

• Sensitivity of 95% for colorectal cancer and 43% for advanced precancerous lesions,
• Specificity of 94% (the rate of detecting colon cancer without false-negative results).

Cologuard Plus also had significantly higher overall sensitivity than FIT, indicating better detection of stage I-III cancer, high-grade dysplasia, and advanced precancerous lesions.

Expected Market Launch in 2025

Exact Sciences plans to launch Cologuard Plus in 2025. The company expects Medicare coverage and inclusion in United States Preventive Services Task Force (USPSTF) guidelines and quality measures. This could make the test more accessible to average-risk individuals and support wider use in colorectal cancer screening.

The Study Behind FDA Approval: Comparing Shield and Cologuard Plus

Cologuard Plus uses stool samples, whereas Guardant Health's newly FDA-approved Shield screens for colorectal cancer using blood. Shield offers a different approach to detecting colorectal cancer and advanced neoplasia.

The FDA's decision on Shield followed a strong recommendation for approval from an advisory committee panel in May 2024. Approval was based on ECLIPSE, a registration study involving more than 20 thousand patients. Designed to reflect the diverse United States population, it was conducted at more than 200 trial sites in rural and urban communities across 37 states.

Chung and colleagues published the results in The New England Journal of Medicine in March 2024. Shield demonstrated 83% sensitivity for colorectal cancer and 90% specificity for advanced neoplasia. This performance falls within the range of existing guideline-recommended noninvasive screening methods, whose overall colorectal cancer sensitivity ranges from 74% to 92%.

Conclusion: New Hope in Colorectal Cancer Screening

Cologuard Plus raises the performance bar with 95% sensitivity for colorectal cancer, 43% sensitivity for advanced precancerous lesions, and 94% specificity. Through improved sensitivity, it aims to minimize unnecessary follow-up colonoscopies and offer a less invasive approach. Exact Sciences also expects Medicare coverage, guideline inclusion, and widespread use in 2025.

Widespread use of Cologuard Plus could make an important difference in detecting early cancer and precancerous lesions. Blood-based tests such as Shield could meet different needs by expanding noninvasive screening options. Broader uptake of these next-generation tests could be an important step in preventing and treating colorectal cancer at both individual and population levels.