Proximal shift of colorectal cancer. A persistent phenomenon with multiple causes, patterns and clinical implications.

A considerable change in the anatomical distribution of colorectal cancer (CRC) towards more proximal sites has been observed in Western countries within the last 6-7 decades. As a result, tumors located proximally to the splenic flexure are now accounting for 30-40% (or even more) of overall CRC cases. This proximal migration is not always representing a true increase of proximal cancer, arising from various combinations of changes in the rates of proximal and distal cancer (e.g. proximal increase with distal stability/reduction, or decline in both sites albeit higher distally etc) in different areas and periods. Principal potential causes include ageing in Western populations (since proximal cancers are more common among the aged), various potentially site-specific exposures (lifestyle and medical) and systematic screening. Their effect is reflected in the particular shift patterns; for instance, widespread screening in USA has led to an overall CRC decline, more evident distally (for technical, anatomical and morphological reasons). Segmental disparities in particular characteristics (age, gender, morphology) and responses to various exposures are etiologically associated (for the most part) with underlying genetic differences between proximal and distal tumors. From clinical aspect, proximal shift necessitates a more generalized use of colonoscopy in screening programs. Potential interventions in treatment (segmental patient stratification) and prevention (identification of particular site-specific exposures) require further investigation.