Best choice for colorectal cancer screening at the population level: fecal immunochemical test, stool DNA test, or...

Fecal immunochemical testing (FIT) remains the cornerstone of organized, population-based colorectal cancer (CRC) screening owing to its noninvasive nature, affordability, and proven mortality reduction. FIT facilitates early detection; however, its population impact depends on sustained participation, adequate colonoscopy capacity for positive results, and data-driven optimization of thresholds and intervals. Stool DNA-based tests offer higher sensitivity for CRC and advanced adenomas than FIT, with lower specificity and higher costs. Multitarget stool DNA tests may serve as complementary options within hybrid risk-stratified strategies; however, further evidence is needed regarding their long-term effectiveness, programmatic feasibility, and economic sustainability before widespread adoption at the population level. In contrast, methylation-based stool DNA tests utilize stable epigenetic alterations and simpler laboratory workflows, offering advantages in logistics, scalability, and cost-effectiveness, and thus represent promising candidates for organized screening. Colonoscopy remains the most comprehensive screening modality, enabling the detection and removal of precancerous lesions, thereby preventing the development of CRC. However, its use as an organized screening tool at the population level is limited by its invasiveness, cost, logistical complexity, and suboptimal participation, which compels most organized programs to position colonoscopy primarily as a confirmatory test following noninvasive screening rather than as a universal first-line modality.