Fecal DNA Biomarkers for the Detection of Colorectal Neoplasia: Attractive, but Is It Feasible?

Because of the high mortality associated with advanced disease, accessibility to direct visual examination, extensive research, and recognition of the genetic mechanisms associated with its carcinogenesis, the colon and rectum have emerged as an important model for the introduction of innovative and effective cancer screening and early detection tools for large populations. Wide-scale screening using fecal occult blood testing (FOBT) results in 15%–33% reduction in colorectal adenocarcinoma mortality, but at the expense of many unneeded colonoscopies ( 1 – 6 ) . Despite specificity of approximately 95% and reasonable cost-effectiveness, FOBT's test sensitivity ranges from 15% to 30% ( 7 ) , leaving room for substantial improvement. Traditionally low FOBT sensitivities, reflecting standard office practice ( 8 , 9 ) , may be improved when employed in an organized, structured program ( 10 , 11 ) . The addition of sigmoidoscopy to FOBT increases the detection of adenomas by approximately twofold over FOBT alone, but there are no data demonstrating enhanced mortality reduction ( 7 ) . Colonoscopy, with estimated sensitivity exceeding 90% for detection of adenocarcinoma and large adenomas and specificity exceeding 99%, requires a thorough bowel preparation and sedation, causes patient discomfort and small but nonnegligible risk of major complications ( 7 , 12 – 17 ) . In a recent analysis, colonoscopy has a reported cost-effectiveness of $17 010 incremental costs per life-year gained ( 18 ) . Although differences in model assumptions will result in different incremental costs per life-year gained, colonoscopy is considered to have borderline cost-effectiveness as a screening tool for detection of adenocarcinoma of the colon.