Prevention and early detection of colorectal cancer

Almost 1.4 million new cases of colorectal cancer occur per year world-wide. In the United States, 137,000 new cases and 51,000 related deaths have been estimated for 2014. With globalization, CRC has become a highly prevalent disease in developed countries. Age-adjusted rates per 100,000 in Japan currently exceed those of the US. The long natural history of colorectal neoplasia affords the opportunity to improve survival through preventive measures. While life-style issues (diet,obesity,low physical activity) contribute significantly to risk, they are difficult to affect on an individual basis. Rapid growth of knowledge about the molecular characteristics of cancers has provided useful insights into the pathogenesis of CRC and identification of early lesions. Evolving knowledge is allowing the development of new tools to identify those who will benefit most from preventive measures such as screening and chemoprevention. Currently screening for adenomatous polyps and early-stage cancers provides the best opportunity to improve survival. Professional societies have established evidence-based guidelines for screening, but the recommended primary modality depends not only on individual test effectiveness, but cost-effectiveness when used in programmatic screening. The growing use of colonoscopy as a primary modality or in a two-step screening paradigm requires the institution of quality measure to reduce the rate of interval cancers. While the highest impact form of prevention is CRC screening, the development of effective, inexpensive, and safe chemopreventive agents would be of great benefit. Chemoprevention of CRC through the use of agents to prevent the progression of precursor lesions is a concept that is finding growing acceptance. Initial enthusiasm was based on epidemiology, animal trials, small clinical trials using biomarkers, and trials in high-risk groups. The results of prospective, randomized trials relevant to the general population have in many cases been less impressive, but a number of recent trials have provided evidence that chemoprevention of colorectal neoplasia may become a reality. What is acceptable in terms of safety will depend on the risk for cancer development in a given population, the magnitude of risk reduction (preferably measured in reduced mortality), and the toxicity of a given agent. Successful chemoprevention could supplement the benefit of screening colonoscopy by targeting missed lesions, addressing the development of interval lesions, decreasing the number of adenomas needed to be removed at future colonoscopy, and slowing the growth of early cancers.