Quantitative Immunochemical Fecal Occult Blood Tests: Is It Time to Go Back to the Future?

Colorectal cancer (CRC) screening rates remain low, despite the fact that it has been nearly 6 years since Medicare and others began reimbursing for screening colonoscopy. Although the proportion of persons age 50 years and older who have had sigmoidoscopy or colonoscopy has increased from 33% in 1999 to 52% in 2004 (1), CRC screening rates still lag behind those of breast and cervical cancer. We need more convenient and less invasive screening tests. Could a fecal occult blood test (FOBT) fit the bill?

Annual or biennial guaiac-based FOBT screening reduces CRC incidence by 17% to 20% (2) and CRC mortality by 16% to 33% (3–5). Guaiac-based FOBT measures the peroxidase activity of hemoglobin (6). Its advantages include privacy, noninvasiveness, and cost-effectiveness. Drawbacks include limited sensitivity for detecting cancer (and worse sensitivity for detecting advanced polyps), the need for periodic testing, and low patient adherence. Another disadvantage is poor specificity (or high false-positive rate); guaiac-based FOBT reacts with nonhuman heme in food and blood from the upper gastrointestinal tract. Efforts to develop a more sensitive guaiac-based FOBT have produced tests with poor specificity (6).

Immunochemical FOBTs (I-FOBTs) were developed to improve specificity and eliminate the need for dietary restriction. They use 1 or more monoclonal antibodies or polyclonal antibodies to detect human hemoglobin (7). The U.S. Food and Drug Administration approved the use of an I-FOBT in 2001 as a qualitative test (that is, positive or negative). Soon afterwards, the American Cancer Society recommended using I-FOBTs instead of guaiac-based FOBTs because the former tests were more patient-friendly and had similar or better sensitivity and specificity (7). In a Japanese study of nearly 22 000 asymptomatic patients who had screening colonoscopy over a 20-year period, a single sample I-FOBT had sensitivities of 66% for detecting cancer …