Colorectal Cancer _ ___________________________________________________________________________
Fecal Occult Blood Tests In FOBT testing, the patient collects stool samples that are analyzed for presence of blood. Different FOBT tests involve different collection approaches but commonly require collection of consecutive stool specimens for up to three days. The first FOBTs to enter clinical use were guaiac-based (gFOBT); more recent versions employ immunochemical tests (iFOBT) or markers of DNA mutation (stool DNA tests or sDNA) [1]. Colorectal lesions and adenomatous polyps tend to bleed, and the resulting presence of hemoglobin in stool that is detectable even with intermittent or minimal bleeding formed the basis for gFOBT use in colorectal cancer screening. Hemoglobin is used as a biomarker for detecting blood in stool with guaiac, which identifies peroxidase-like activity that characterizes hemoglobin. However, gFOBT cannot discriminate human from nonhuman or intact from partially digested hemoglobin and is being phased out of clinical use. This results in detection of blood from ingested meat and upper airway and gastrointestinal bleeding as well as colorectal lesions. The low specificity of gFOBT requires confirmatory colonoscopy to validate positive findings [159]. iFOBT was developed to detect intact human hemoglobin originating from colorectal tissue. Unlike gFOBT, it does not detect hemoglobin from nonhuman dietary sources or partly digested human hemoglobin originating from the upper respiratory or gastrointestinal tract [160]. The sDNA variation of FOBT incorporates markers of DNA mutation that detect molecular genetic changes associated with colorectal cancer
PRACTICE GUIDELINE RECOMMENDATIONS FOR COLORECTAL CANCER SCREENING American College of Physicians The American College of Physicians (ACP) published their practice recommendations for colorectal cancer screening based on the review and synthesis of guidelines for screening colorectal cancer produced by several other professional organizations. Several tests to detect adenomatous polyps and cancer were evaluated for colorectal cancer screening efficacy, including flexible sigmoidoscopy, colonoscopy, DCBE, and CT colonography. Tests to primarily detect cancer (e.g., gFOBT, iFOBT, and sDNA) were also assessed [84]. Screening Initiation The ACP recommends that individualized assessment of colorectal cancer risk should be performed in all adults [84]. Average-risk patients should begin at 50 years of age with a stool-based test, flexible sigmoidoscopy, or optical colonoscopy [163]. High-risk patients should begin at 40 years of age or 10 years younger than age of colorectal cancer diagnosis in the youngest family member. Test selection should be based on the benefits and harms of the specific test, the availability of the test, and patient preference. Screening is not recommended in adults older than 75 years of age or with a life expectancy of less than 10 years [84; 163]. Note: The National Cancer Institute disputes recommendations of initiating colorectal cancer screening 10 years before the age at diagnosis in the youngest family colorectal cancer case, stating that direct evidence or strong rational argument is absent for aggressive screening methods in patients with modest family history of colorectal cancer [1]. In response to rising rates of colorectal cancer among persons younger than 50 years of age, the U.S. Preventive Services Task Force (USPSTF) lowered its recommended age of initiation of screening to 45 years of age, though the strength of recommendation is slightly lower than for those 50 years of age and older [121]. Clinical Considerations and Best Practice Advice for Colorectal Cancer Screening African American individuals with average risk should begin colorectal cancer screening at 40 years of age due to the higher colorectal cancer incidence and mortality rates. Healthcare professionals should consider patients’ personal, cultural, and religious preferences in screening test selection. For example, annual FOBT is not a good strategy for patients who may be unwilling or unable to follow-up yearly. Some women prefer a female endoscopist, and colonoscopy by a male endoscopist should be recommended only after discussion and patient consent.
gene mutations shed into the stool [161]. Potential Complications and Harms
The very low sensitivity of gFOBT leads to a high proportion of false-positive results when confirmed by colonoscopy or DCBE plus flexible sigmoidoscopy, which a systematic review of published clinical trials estimated at greater than 80% [162]. iFOBT is increasingly recognized as superior to gFOBT for sensitivity, accuracy, and compliance, and it shows greater ability in detecting advanced neoplasia. While iFOBT requires colonoscopy confirmation of positive results and cannot detect many precancerous polyps, higher participation in iFOBT than in colonoscopy screening may offset some of its comparative limitations [120]. DNA fecal testing is emerging as a potentially important addition to the stool-based tests for colorectal cancer screening. More research is needed to understand the role of sDNA testing in organized colorectal cancer screening and unaddressed factors, such as screening interval, patient adherence, and costs [120].
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