From the Guidelines
Cologuard is a non-invasive screening test for colorectal cancer that works by detecting altered DNA and blood in stool samples, with a sensitivity of 92.3% in detecting CRC, as shown in a study of 9989 participants 1. The test requires you to collect a stool sample at home using a kit provided by your healthcare provider. Once collected, you send the sample to a laboratory where it's analyzed for specific DNA mutations, including KRAS mutations, aberrant NDRG4 and BMP3 methylation, and ACTB, in conjunction with a hemoglobin immunoassay 1. The test looks for abnormal changes in DNA that occur as cells in the colon lining become cancerous, as well as microscopic amounts of blood that might be released by polyps or tumors. Some key points to consider about Cologuard include:
- It is more sensitive than fecal immunochemical test (FIT) in the detection of CRC, advanced precancerous lesions, polyps with high-grade dysplasia, and sessile serrated polyps larger than 1 cm 1
- However, it has a lower specificity compared to FIT, with 86.6% vs 94.9% among participants with nonadvanced or negative findings 1
- The test is effective because cancer cells and precancerous polyps shed DNA into the stool as they grow, and these genetic changes can be detected before symptoms appear
- A positive result will still require follow-up with a diagnostic colonoscopy to confirm findings The FDA approved Cologuard as the first stool DNA test for primary screening of CRC in August 2014, and it is recommended every three years for average-risk adults aged 45 and older as an alternative to colonoscopy 1.
From the Research
Mechanism of Cologuard
- Cologuard is a multi-target stool DNA test that detects colorectal cancer (CRC) non-invasively 2, 3, 4.
- The test combines the detection of haemoglobin with DNA methylation markers (NDRG4 and BMP3) and KRAS mutations 4.
- It is designed to identify genetic alterations in the adenoma-cancer sequence, allowing for early detection of CRC 5.
How Cologuard Works
- The test analyzes a stool sample for the presence of abnormal DNA and haemoglobin 3, 4.
- The abnormal DNA is detected through the identification of specific genetic mutations and methylation markers 2, 4.
- The presence of haemoglobin in the stool sample indicates bleeding in the gastrointestinal tract, which can be a sign of CRC 2, 4.
Effectiveness of Cologuard
- Studies have shown that Cologuard has a positive predictive value (PPV) of 1.3% for colorectal cancer and 7.7% for precancerous lesions plus colorectal cancer 6.
- While Cologuard is a non-invasive screening tool, its detection accuracy remains unsatisfactory, and it is not cost-effective 4.
- The test has been shown to increase colorectal cancer screening in otherwise non-compliant Medicare patients due to its non-invasive nature 6.