The FDA recently approved Cologuard Plus, the next generation of the Cologuard fecal DNA test used to screen for colon cancer. Cologuard Plus includes a new molecular panel intended to improve the test's specificity (i.e., fewer false positives). Like the original Cologuard test, a fecal immunochemical test (FIT) is performed with the DNA assay. If either test is positive, results are deemed positive without details on the individual tests. Cologuard Plus was evaluated in the BLUE-C cohort study, where 20,176 participants 40 years and older (average age 63 years) took the test before undergoing screening colonoscopy. The original Cologuard test was evaluated in a similar study published in 2014. A comparison of how the two tests performed is presented in the table below.

• PMID 38477986, PMID 24645800

Measure	Cologuard	Cologuard Plus
Colorectal cancer (Sensitivity)	92.3%	93.9%
Colorectal cancer (Specificity)	89.8%	92.7%
Precancerous lesion (Sensitivity)	42.4%	43.4%

While the absolute difference in specificity may seem small (2.9%), when applied to a large screening population, the improvement is meaningful. Consider the following: Since its launch in 2014, over 16 million Cologuard tests have been processed. Assuming 2 million tests are performed annually on a population with a colorectal cancer prevalence of 0.3%, an improvement in specificity of 2.9% equates to 57,826 fewer false positives (and follow-up colonoscopies) per year. On the sensitivity side, a 1.6% improvement means 96 fewer cancer cases will be missed. Presumably, the manufacturer, Exact Sciences, will now phase out Cologuard and replace it with Cologuard Plus.

• Colon cancer screening recommendations (average-risk)
• Colon cancer screening recommendations (increased-risk)