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Establishment of screening programs has allowed earlier diagnosis and understanding of early steps of pathogenesis of CRC.

Considering that approximately three-quarters of colorectal cancers are located in the sigmoid colon and rectum, it seems reasonable to use flexible sigmoidoscopy as a screening tool, particularly as the finding of a significant distal adenoma (see Figure 1) may act as an indicator of more proximal disease. Based on these premises, it has been initially proposed that a single flexible sigmoidoscopy at about the age of 60 years with removal of all adenomas at the time of examination and performing colonoscopy for this at high risk for adenoma or cancer would be an effective screening modality for colorectal cancer (Atkin et al. 2001). In addition, this strategy might be expected to reduce the incidence of colorectal cancer by removal of adenomas. Compliance with screening using sigmoidoscopy was reported to range between 46.6% and 71% (Atkin et al. 2017; Segnan et al. 2011; Verne et al. 1998). This compliance could be increased from 46.6% to 61.8% when associated with telephone reminders (Verne et al. 1998). In terms of findings, polyps are found in 19.3%, adenomas in 6.8% and colorectal cancer in 0.4% of sigmoidoscopies performing in patients aged 50–75 years (Verne et al. 1998). Screening using flexible sig­moidoscopy with a repetition at year three or five was demon­strated to decrease the incidence of colorectal cancer (relative risk: 0.82) and mortality (relative risk: 0,75) after approximately 16 years when compared to usual care. This reduction of mortality was limited to the distal colon, where sigmoidoscopy allowed early detection of precursor lesions and cancer (Miller et al. 2019). In per protocol analysis, reduction of the incidence (by 31–35%) and the mortality (by 38–43%) in patients screened by flexible sigmoidoscopy when compared to non-screened patients was confirmed by other randomized controlled trials,

even if the examination was performed only once (Atkin et al. 2010; Atkin et al. 2017; Holme et al. 2014; Segnan et al. 2011). In England, national flexible sigmoidoscopy screening has recently been stopped in favor of initial FIT testing and recommenda­tion for a colonoscopy for patients who are FIT-positive.

When compared to other screening modalities, colonoscopy performs well but suffers from low uptake. For instance, a randomized controlled trial, including approximately 30,000 subjects, compared screening using 4 rounds of FIT (and colo­noscopy if positive), once-only flexible sigmoidoscopy (and completion colonoscopy if worrisome findings) and once-only colonoscopy. Of note, compliance with the screening program was higher for FIT (73%) and lower for flexible sigmoidoscopy (31%) and colonoscopy (24%). As a corollary, in intention-to­treat screen analysis, FIT allowed identifying more cases of advanced colorectal neoplasia (4.5%) than both flexible sigmoid­oscopy (2.3%) and colonoscopy (2.2%). When looking at patients who received screening (per protocol analysis), colonoscopy was the most efficient screening modality (9.1% of advanced colo­rectal neoplasia), followed by flexible sigmoidoscopy (7.4%) and FIT (6.1%). Finally, both endoscopic techniques led to less false negative results. For instance, interval colorectal cancer was found in 0.13% of patients with negative FIT, when compared to

These biases are volunteer bias, length bias, and lead-time bias. Volunteer bias results from the fact that invitations to be screened are more likely to be accepted by those who are health conscious than those who are not. Therefore, people who accept invitations to be screened are likely to have a better