Central role of colonoscopy in screening for colorectal cancer:
Colonoscopy is – irrespective of first line screening test – the final common pathway of all screening for colorectal cancer (CRC), and is used for biopsy and polyp removal. For a screening-test in the (healthy) general population colonoscopy is invasive and prone to (unlikely) serious complications. Screening-yield and rates of complications are strongly dependent on the individual operator and on quality assurance. As a result, training and continued education of endoscopists as well as monitoring of both detection and complication rates are key to high screening-quality.

Effectiveness of screening for CRC:
No data is currently available on the impact of CRC-screening on all-cause mortality. Four randomized controlled trials on screening for fecal occult blood as a first-line test (gFOBT) showed a relative risk reduction of 15% for disease-specific CRC-mortality. Absolute risk reduction was between 0.12-0.29%. Two large non-population based randomized controlled trial on once-only flexible sigmoidoscopy as a first-line screening-test showed a relative risk reduction of 31% and 22% (statistically not significant) for disease-specific CRC-mortality and a reduction of CRC incidence of 23% and 18%. Results from a large non-population based two round flexible sigmoidoscopy screening study showed a relative risk reduction of 26% of disease-specific CRC-mortality and a reduction of CRC incidence of 21%. Absolute risk reduction of CRC-mortality through flexible sigmoidoscopy was between 0.11-0.15%. Results from a population based randomized trials on flexible sigmoidoscopy are expected in 2013. To date there is no evidence from randomized controlled trials on CRC-screening using colonoscopy as a first-line screening test. Two randomized studies on screening with either colonoscopy or iFOBT as a first-line test will yield results starting ten years from now. There is only limited evidence on test characteristics (sensitivity, specificity, complication rates) in real life screening-settings. The ideal test strategy in CRC-screening is uncertain, the evidence base evolving.

Choice of first-line screening-test:
When considering first-line screening-tests on which to base an organized program, program sensitivity per invitee through the test's impact on participation in screening (and re-screening) is more important than single test-sensitivity per screened participant. Complications rates are to be taken into account. Program-sensitivity largely depends on participation rates. Recent developments in first-line screening tests include quantitative iFOBTs. CT-colonoscopy, capsule endoscopy and new molecular tests are not yet viable alternatives for use in population-based mass-screening.

Improving screening-effectiveness:
An upper age-limit for CRC-screening is recommended. An integrated screening-program combines screening with screening-relevant considerations in diagnosis, treatment and surveillance. Along with standardized documentation and regular evaluation an integrated program-design provides the quality necessary to consider screening average risk-populations. Giving thorough attention to the design of the surveillance regime is important, because its thresholds determine the numbers of surveillance-colonoscopies resulting from CRC-screening. Incremental implementation of a national population-based screening-program, with targeted research studies, pilot testing and incremental roll-out, like in the Netherlands, should be considered.

Securing comprehensive program-financing:
Population-based screening-programs require significant initial investment in overhead and sustainable financing of ongoing documentation, quality assurance and evaluation. Also, ongoing financing of both program- and provider-independent information dissemination to potential screening-participants enabling informed consent if or if not to participate in screening, and funds for regular program evaluation through an external institution need to be secured.