The following non-invasive stool tests for
colorectal cancer (CRC) screening exist:
guaiac or immunochemical fecal occult blood testing (FOBT), genetic stool tests and the M2-PK. Currently the most widely used tests are
guaiac-based (gFOBT). Several randomized controlled trials have shown that gFOBT are able to achieve a reduction in CRC-related mortality. This reduction is achieved by detecting asymptomatic
cancers at an early stage with a better prognosis. However, gFOBT have a low sensitivity for colorectal
adenomas and are thus unlikely to be able to reduce the incidence of CRC. Furthermore, gFOBT are not specific for human blood and can be influenced by external factors. Immunochemical tests (iFOBT) only detect human blood in the stool. In two recent randomized studies from the Netherlands comparing
guaiac and immunochemical tests in the asymptomatic population, iFOBT were found to detect more
cancers than gFOBT. Furthermore, iFOBT were able to detect more advanced
adenomas thus having the potential to be able to reduce the incidence of CRC as well as CRC-related mortality. In the recently released European CRC screening guidelines, iFOBT are considered the screening test of choice. Several questions remain however. It is currently unknown what the optimal cut-off value for an iFOBT to be considered positive should be and what the number of stool samples is that are required. Genetic stool tests detect mutations in stool that can be found in CRC. The original test testing for 21 genetic changes was found to be superior to gFOBT for the detection of
cancers. However, the sensitivity was moderate (51.6%) and the sensitivity for advanced
adenomas was low. In the meantime the test has been modified improving
DNA extraction and reducing the number of mutations tested for as well as including a methylation marker. The efficacy of the modified test in the screening population is unknown. M2-PK is an isomer of the
enzyme pyruvate kinase that is involved in glycolysis. Studies have found a good sensitivity for
cancers, a low sensitivity for advanced
adenomas with a specificity of around 80%. Further studies in the screening population are required.