New England Journal of Medicine Publishes the Science Powering the Next-Generation Cologuard Test

Almost exactly 10 years ago, the scientific research behind Cologuard^® made its first appearance in the New England Journal of Medicine. 
 
It was a watershed moment for Exact Sciences. Scientists had been working for years to figure out how to detect colorectal cancer (CRC) by analyzing patients’ stool. After the journal published results in March 2014 from the company’s pivotal DeeP-C trial, which included 10,000 patients, Exact Sciences brought Cologuard to market. For the first time, patients could screen for CRC at home using a test that looked for both abnormal DNA and blood in stool.
 
A decade later, Exact Sciences has reached another major milestone. In its March 14, 2024, print issue, The New England Journal of Medicine published results from BLUE-C, a clinical trial designed to evaluate the performance of the next-generation Cologuard® test. Read the press release.

The BLUE-C clinical trial 

BLUE-C is one of the largest CRC screening trials ever conducted. It is a pivotal trial, meaning a clinical study conducted to show the safety and effectiveness of a product for its intended patient population.  
 
Exact Sciences designed BLUE-C to support health equity and to help ensure that the next-generation Cologuard test will meet the needs of all who use it. As a result, the study population of more than 20,000 screen-eligible participants reflects the racial and ethnic makeup of the United States according to the 2020 census.^{1, 2}    
 
BLUE-C assessed the sensitivity and specificity of the next-generation Cologuard test for CRC and advanced precancerous lesions. It also compared the next-generation Cologuard test with FIT (fecal immunochemical test),³ a widely used stool-based test. Learn more about sensitivity and specificity. 
 
Published BLUE-C results show that the study met all endpoints. The next-generation Cologuard test demonstrated high cancer sensitivity and specificity. It showed the ability to detect 75% of high-grade dysplasia, a concerning type of precancerous growth. 
 
The test also was significantly more likely to detect cancer or precancer when compared to FIT.⁴ Learn more about the BLUE-C clinical trial.
 
Exact Sciences believes this next-generation test demonstrates a new performance standard in non-invasive CRC detection. 

The New England Journal of Medicine 

Publishing clinical trial results is a significant step toward Exact Sciences bringing the next-generation Cologuard test to patients.  
 
A company seeking regulatory approval for a new test will submit results from clinical trials and other data to a regulatory body, such as the Food and Drug Administration (FDA). When results from a clinical trial appear in a peer-reviewed journal, that adds credibility to the science. It means that experts in the field have reviewed the results and deemed them reliable to publish. 
 
The influential New England Journal of Medicine delivers peer-reviewed research and other content to the medical community. More than 1 million people around the world read it in print and online each week. It has been published continuously for more than 200 years. 
 
The journal says it receives more than 16,000 research submissions each year to be considered for publication. More than half come from outside the United States. Only about 5% of submissions are published. 
 
Exact Sciences has submitted BLUE-C results to the FDA in support of regulatory approval for the next-generation Cologuard test. Pending approval, the test is expected to be available in 2025. 
 
As it looks to the future, the company in 2024 will mark the 10th anniversary of the Cologuard test. Exact Sciences is celebrating the innovation and teamwork that led up to the 2014 DeeP-C study publication and went on to deliver a critical CRC screening test to patients and to those who provide their health care.    

The impact of Cologuard  

~90% 

The percentage of CRC cases that are treatable when caught in early stages^{*, 5} 
 

14 million+ 

The number of times people have used the Cologuard test to screen for CRC^†  
 

500,000+

The number of times the Cologuard test is estimated to have detected precancerous polyps or early-stage CRC in patients^‡ 
 

60 million+

The number of eligible Americans currently unscreened or under-screened for CRC^{6, 7} 
 

JODY HOYOS, CEO, Prevent Cancer Foundation®  

“Exact Sciences continues to be an inspiration for innovation across the cancer screening space. Every step of the process that led to the availability of Cologuard was charting new territory. The fact that it was done successfully and with thoughtful consideration for the people that would be using these tests gives inspiration to the field.  
 
“The impact on public health goes beyond the increase in colorectal cancer screenings being achieved. It’s an example that it is possible to make significant, positive changes in our healthcare system.” 
 

KATIE COURIC, journalist, media personality, and cancer screening advocate  

“I lost my first husband to colon cancer when he was just 42 — our girls were 6 and 2. But colon cancer is a disease that’s treatable when detected early. Please talk to your doctor to see if you are eligible for colorectal cancer screening. Whether you choose a procedure like colonoscopy or a noninvasive, at-home test like Cologuard, what matters most is that you get screened. I’m so grateful that Cologuard has helped so many people take necessary steps to care for their health.” 
 

MICHAEL SAPIENZA, CEO, Colorectal Cancer Alliance 

“My mom was diagnosed with colorectal cancer when she was 56 years old. She never got screened, and if she had been screened, she'd be alive today, period. She had a prescription for colonoscopy and FIT that had not been done.  
 
“We will not end this disease in our lifetime if we don't have at-home stool tests. Human nature is human nature — people want to have alternatives. There’s been study after study that has shown that. Stool tests and noninvasive tests like Cologuard will continue to have a huge impact in saving lives.” 
 

YLA FLORES, CRC survivor who screened with Cologuard 

“Colon cancer doesn’t care about race, gender, creed. It does not discriminate. People need to take it seriously. Cologuard makes it easy for everyone to get screened.” 
 

Notes and references

Cologuard is the first FDA-approved, noninvasive, at-home stool-based CRC screening test for average-risk individuals 45 years or older. Rx only. The next-generation Cologuard test has not been cleared or approved by the U.S. Food and Drug Administration (FDA) or any other national regulatory authority. 

* Based on 5-year survival.

† Based on internal data.

‡ Based on extrapolated data from the pivotal DeeP-C study.

1. Imperiale T, et al. Oral Presentation 54, ACG 2023.

2. United States Census Bureau. Annual Estimates of the Resident Population by Single Year of Age and Sex for the United States: April 1, 2020, to July 1, 2022 (NC-EST2022-AGESEX-RES). Accessed 16 October 2023. https://www.census.gov/data/tables/time-series/demo/popest/2020s-national-detail.html

3. Polymedco OC-Auto® Micro 80 iFOB Test

4. Polymedco OC-Auto® Micro 80 iFOB Test

5. National Cancer Institute. SEER cancer stat facts: colorectal cancer. Accessed Aug. 30, 2023. https://seer.cancer.gov/statfacts/html/colorect.html 

6. United States Census Bureau. Annual Estimates of the Resident Population by Single Year of Age and Sex for the United States: April 1, 2020, to July 1, 2022 (NC-EST2022-AGESEX-RES). Accessed 10May2023. https://www.census.gov/data/tables/time-series/demo/popest/2020s-national-detail.html

7. ACS. Colorectal cancer facts and figures 2023-2025. Atlanta: American Cancer Society; 2023.