Establishing a biological profile for interval colorectal cancers

Colorectal cancer (CRC) remains the second leading cause of cancer-related deaths in North America. Screening for CRC and its precursor lesions is highly effective in reducing the incidence and deaths due to the disease. However, there remain a substantial number of individuals who are diagnosed with CRC soon after a negative/clearing colonoscopy with no documented evidence of CRC. The occurrence of these interval CRCs (I-CRCs) reduces the effectiveness of CRC screening and detection tests and has only recently attracted wide spread attention. I-CRCs can be subdivided into those that occur most likely due to the failure of the colonoscopy examination (missed CRC and CRC that developed from missed or incompletely resected precursor lesions) and those that develop rapidly after the colonoscopy (de novo I-CRCs). In this review, we discuss the current literature and present both the clinical and biological factors that have been identified to account for I-CRCs, with a particular focus on the aberrant molecular features that are candidate causative agents for I-CRCs. We conclude additional studies are required to fully understand the molecular features that lead to the development of I-CRCs, which in turn is essential to develop measures to prevent the occurrence of this group of CRCs and thereby improve CRC screening and detection strategies.