Colorectal cancer screening: prospects for molecular stool analysis

Colorectal cancer (CRC) is amenable to screening: it has a recognizable early stage and a defined natural history; surgical treatment of malignancy is effective; and pre-malignant lesions can be removed if detected. However, it is not yet clear whether screening should target early cancers or pre-malignant adenomas.Current screening tests either detect the presence of blood in stool (faecal occult blood testing) or identify gross abnormalities (for example, flexible sigmoidoscopy and colonoscopy). All current tests are limited in patient acceptability and/or effectiveness.There are prospects for new screening tests based on increased understanding of the biology and natural history of CRC. There is considerable interest in stool testing, which is non-invasive; does not require bowel preparation; potentially enables screening of the entire length of the colon and rectum; and produces specimens that are transportable.One category of stool test involves detecting cells or cell contents in stool, for which colonocytes are likely to be a better target than blood. Biomarkers such as minichromosome maintenance proteins could indicate the presence of CRC cells in stool and/or facilitate the identification of such cells following colonocyte isolation.An alternative approach involves testing for abnormal DNA in stool, using target genes identified as being abnormal in the colorectal adenoma–carcinoma sequence. Individual DNA tests generally have high specificity but low sensitivity, so multitarget DNA assays have been developed.Large-scale evaluation of candidate tests, either singly or in combination, is now required. Of particular value would be randomized controlled trials showing a reduction in CRC incidence and/or mortality in the tested individuals.An effective screening strategy would produce extra health-care provision costs, although these would be balanced by a reduced requirement to treat patients with established CRC. 'Halo effects' of an effective screening test would produce benefits for patients with symptomatic CRC as well as the screened population.