Colorectal cancer is the second-leading cause of cancer death in the United States. Colorectal cancer is most frequently diagnosed among adults aged 65 to 74 years. The median age at death from colorectal cancer is 68 years. The USPSTF recommends screening for colorectal cancer in all adults aged 50 to 75 years (A recommendation). It also recommends screening adults aged 45 to 49 years (B recommendation). USPSTF recommends that clinicians selectively offer screening to adults aged 76 to 85 years (C recommendation). Evidence indicates the benefit of screening all persons in this age group is small.
The harms of screening for colorectal cancer in adults aged 50 to 75 years are small. The majority of harms are related to colonoscopy, either as a screening test or as follow-up for positive findings detected by other screening tests. USPSTF estimates there are 4 perforations and 8 major bleeding events per 10,000 colonoscopies. Colonoscopy risks increase with age.
Several options are available for colorectal cancer screening including fecal-based tests, endoscopic tests and imaging. USPSTF did not express a preference for one type of testing over another. Colonoscopy is by far the most commonly used method for colorectal cancer screening in the United States. However, no randomized clinical trial has been published showing that colonoscopy reduces colorectal cancer mortality. In contrast, multiple randomized clinical trials (RCTs) have shown that screening with guaiac-based fecal occult blood test (gFOBT) reduces colorectal cancer deaths.
FOBT is based upon the principle that advanced adenomas and colorectal cancer are friable lesions that leak trace amounts of blood as a result of stool trauma and contractions of the colon. The overall specificity of guaiac FOBT has varied in the literature, ranging from 88% to 98%. Compared to colonoscopy, sensitivity is only 12% for advanced adenomas and 26% for colorectal cancer.
To improve sensitivity of FOBT, Beckman Coulter developed two newer versions, Hemoccult II and the Hemoccult II SENSA. Hemoccult II has a sensitivity of 25% to 38% and a specificity of 98% to 99% according to the US Preventive Services Task Force. Hemoccult SENSA has a sensitivity of 62% to 79% and a specificity of 87% to 96% for detecting colorectal cancer. Although this test has improved sensitivity over the previous versions, it has lower specificity and, therefore, more false-positive results.
Immunochemical FOBT (iFOBT) or fecal immunochemical test (FIT) were developed to specifically detect intact human hemoglobin. This test uses monoclonal antibodies directed against the globin moiety of human hemoglobin. These antibodies do not react with hemoglobin from nonhuman dietary sources. They also do not detect partly digested human hemoglobin from the respiratory or upper gastrointestinal tract. Thus, FIT is more specific than gFOBT. Hemoccult ICT (Beckman Coulter) and OC FIT-CHEK by Polymedco are the two most popular brands of FIT available in the United States. According to USPSTF, OC FIT-CHEK has the highest sensitivity and specificity. Using a cutoff of 10 μg hemoglobin per gram of feces, OC FIT CHEK had a sensitivity that ranged from 79% to 88% and specificity from 91% to 93%. Using the manufacturer’s recommended cutoff of of 20 μg hemoglobin per gram of feces sensitivity ranged from 73% to 75% and specificity from 91% to 95%. USPSTF recommends screening every year by this method.
Multitargeted stool DNA testing (FIT-DNA) is an emerging screening strategy that combines FIT with testing for altered DNA biomarkers in cells shed into the stool. In 2014, the U.S. Food and Drug Administration approved Cologuard (Exact Sciences) as a screening test for colorectal cancer. Cologuard detects both hemoglobin and gene mutations associated with colorectal cancer. Patients with positive test results are advised to undergo a diagnostic colonoscopy.
The safety and effectiveness of Cologuard was established in a clinical trial that screened 10,023 participants for colorectal cancer with Cologuard and a fecal immunochemical test (FIT). Cologuard was more sensitive than FIT. It detected 92 percent of colorectal cancers and 42 percent of advanced adenomas, while FIT detected 74 percent of cancers and 24 percent of advanced adenomas. Cologuard had more false positive results and, therefore, lower specificity than FIT. Cologuard correctly ruled out colon cancer only 87% of the time versus 95% for FIT.
Cologuard’s lower specificity means that an additional 13% of patients will be referred for unnecessary follow-up colonoscopies. However, the less invasive nature of Cologuard may mean that more people might be willing to be screened for colorectal cancer. If everyone was screened with Cologuard, 87% of colonoscopies could be avoided.
Cologuard costs $599 compared to $25 for FIT. Medicare covers the new test once every three years for Medicare beneficiaries who meet all of the following criteria:
- age 50 to 85 years,
- asymptomatic and
- average risk of developing colorectal cancer
Even though Cologuard was not directly tested against colonoscopy, it is being marketed as an alternative. Approval of the Cologuard does not change current practice guidelines for colorectal cancer screening. The United States Preventive Services Task Force (USPSTF) does not recommend stool DNA testing as a method to screen for colorectal cancer. USPSTF recommends adults age 50 to 75, at average risk for colon cancer, be screened using fecal occult blood testing, sigmoidoscopy, or colonoscopy.
In March 2025, launched its Cologuard Plus test after obtaining FDA approval and Medicare coverage. The addition of new genetic biomarkers reduced its false-positive rate while maintaining its sensitivity in detecting advanced precancerous polyps and tumors.
References
United States Preventive Services Task Force, May 18, 2021
Lin JS, Piper M, Perdue LA, et al. Screening for Colorectal Cancer: A Systematic Review for the U.S. Preventive Services Task Force. Evidence Synthesis No. 135. AHRQ Publication No. 14-05203-EF-1. Rockville, MD: Agency for Healthcare Research and Quality; 2016.
Imperiale TF, Ransohoff DF, Itzkowitz SH, , et al. Multitarget stool DNA testing for colorectal-cancer screening. N Engl J Med. 2014;370(14):1287-97.
Premarket approval (PMA) for Epi proColon. US Food and Drug Adminstration. http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfPMA/pma.cfm?id=P130001This link goes offsite. Click to read the external link disclaimer. Accessed April 21, 2016.
Centers for Disease Control and Prevention. Vital signs: colorectal cancer screening test use--United States, 2012. MMWR Morb Mortal Wkly Rep. 2013;62(44):881-8.
Bosch LJW, et al, Stool DNA Test Performance in an Average-Risk Colorectal Cancer Screening Population. Am J Gastroenterol. 2019 Dec;114(12):1909-1918.
How to resolve AdBlock issue? 