Commentary on "A Clinician's Guide to Fecal Occult Blood Testing for Colorectal Cancer".

The 2015 Surveillance, Epidemiology, and End Results database reports 132,700 new colon cancer cases in the United States, with 49,700 estimated deaths. Colon cancer is a potentially preventable disease as a result of its relatively indolent natural history, making it ideal for screening and intervention. According to the American College of Gastroenterology, there are prevention and detection tests for colorectal cancer (CRC) screening. Colonoscopy, flexible sigmoidoscopy, and computed tomographic colonography are classified as prevention tests, whereas stool-based testing options, which include fecal occult blood testing (FOBT), fecal immunochemical testing (FIT), and stool DNA (sDNA), are detection tests. Strictly speaking, colonoscopy and stool blood testing are secondary prevention tests; they detect disease after it has occurred. Primary prevention is to manage the root cause in the general population. These two types of secondary prevention differ in effectiveness, invasiveness, and compliance. In this issue of the Southern Medical Journal, Bechtold and colleagues emphasize the importance of colon cancer screening without defining whom to screen and highlights two main points. Despite colon cancer awareness, participation in screening programs in the United States is estimated to be only 65%. According to Centers for Disease Control and Prevention data of those screened for CRC, colonoscopy was the most commonly used test (61.7%), followed by FOBT (10.4%), and sigmoidoscopy + FOBT combination (0.7%). Men 50 to 64 years old, certain ethnic groups, and people not living in metropolitan areas had lower screening rates. Although colonoscopy is the gold standard, it can have cost and social implications. As such, alternatives such as stool-based tests become invaluable in the clinician’s arsenal, and an understanding of these tools is emphasized in this review article. One principle of stool-based testing is excreted blood (heme) in stool caused by friability of neoplasms such as adenomas or early cancer. Guaiac-based stool tests have evolved through the years, with the newest generation of Hemoccult II SENSA (Beckman Coulter, Brea, CA) having 64% to 80% sensitivity and 87% to 90% specificity. FIT has better performance, with 79% to 91% sensitivity and 91% to 97% specificity for colon cancer detection. These results need to be tempered by FIT testing drawbacks. Allison et al highlight a lack of standardization between cutoff values and the testing kit which both impact sensitivity. Guaiac-based stool tests have some provisos of false-positives with dietary heme content and false-negatives with some medications; therefore, a specific diet is recommended. Multiple stool samples also are required for guaiac-based stool tests. FIT does not have these limitations, hence no special diet is recommended and most medications can be continued. An alternative technology for stool-based testing is sDNA, which is based on the shedding of aberrant colonic cells with certain DNA characteristics. The US Food and Drug AdministrationYapproved test, Cologuard (Exact Sciences, Madison, WI), uses a multitarget approach: seven DNA mutations biomarkers, two DNA methylation biomarkers, one hemoglobin biomarker, and one beta actin. It offers some benefit in being more sensitive in detecting precancerous lesions such as adenomas with high-grade dysplasia, sessile serrated adenomas, and advanced adenoma. There is some lack of specificity of sDNA compared with FIT, however, and therefore it demonstrates poorer performance than FIT in this regard. There are serum methylated DNAYbased tests that are being studied for colon cancer screening. With regard to cost, guaiac-based tests are the least expensive at $1, FIT has a reasonable cost of $30, and the more recently approved sDNA test Cologuard is $599. Stool collection methods vary, with FIT requiring small samples and sDNA-based testing requiring whole stool samples.When used alone, stool-based testing is recommended annually. In addition, the strategy of using stool-blood testing in the interval Invited Commentary