28 June 2013

The Case for Colorectal Cancer Screening Professor Bob Steele University of Dundee 1600-1700 Hall 1A Tuesday 2nd July Bowel Cancer Screening 2013 Given the biases inherent in any form of screening, it is essential that population-based randomised controlled trials are carried out before any national screening programme is introduced. In the field of colorectal screening there have been four such trials carried out using biennial guaiac faecal occult blood testing (gFOBT) and these studies have consistently demonstrated significant reductions in disease specific mortality. As a result, the UK National Screening Committee recommended that a demonstration pilot be carried out, and this was performed in England (Coventry and Warwick) and Scotland (Grampian, Tayside and Fife) starting in March 2000. After a single biennial round of screening with a gFOBT, analysis of the data demonstrated that the short-term outcomes were almost identical to those predicted by the Nottingham Trial and therefore consistent with a significant mortality reduction. The UK Departments of Health therefore took a decision to introduce national screening programmes based on biennial gFOBT and these commenced in June 2007. In the interim, screening continued in the pilot areas in Scotland offering the opportunity for a natural experiment comparing the population offered screening in Scotland with a population matched for age, gender and deprivation that had not been offered screening during the same time interval. This comparison showed a 10% reduction for colorectal cancer specific mortality in the group offered screening and a 27% reduction in those accepting the invitation to be screened. Thus, taking into account the results of the previous randomised trials and the analysis of data from the programme, there is no doubt that the UK Programme prevents colorectal cancer deaths. However, scrutiny of other performance data has revealed significant limitations. Firstly, approximately half of all colonoscopies performed for a positive faecal occult blood test are negative for neoplasia indicating limited specificity. More importantly, over a 6-year period, almost 50% of all cancers diagnosed in the screened population were interval cancers indicating a sensitivity of only around 50%. Further analysis of interval cancers demonstrates that gFOBT is less sensitive for cancer in women than in men and is also less sensitive for both rectal and right-sided cancers when compared with left-sided cancers. Finally, uptake of screening in the UK remains just above 50%, is greater in women than in men and displays a marked deprivation gradient. Therefore, although the UK screening programmes are performing as predicted, there is considerable room for improvement and alternative strategies are being sought. The MRC/ICRF Trial of single flexible sigmoidoscopy (FS) between the ages of 55 and 65 demonstrated not only a significant reduction in colorectal cancer mortality but also a reduction in disease incidence consequent on removal of adenomas. As a result of this study, a commitment has been made to roll out FS screening before the age of 60 throughout England. Concerns remain, however, regarding the practicalities of delivering of FS and the uptake that can be achieved in an unselected population. Alternative approaches include the introduction of quantitative faecal immunochemical testing (FIT) as the first line test. FIT has several advantages. Firstly, unlike the guaiac test, it is specific for human haemoglobin. Secondly, it is associated with a higher uptake owing to its user friendly design and thirdly, as it is quantitative, the cut off used to trigger colonoscopy can be adjusted in order to obtain the optimal balance between sensitivity and colonoscopy capacity. Quantitative FIT also opens up the possibility of multi-modal risk prediction by employing not only faecal haemoglobin levels but age, gender, deprivation and genetic risk. In summary, the principle that early detection of colorectal cancer by screening reduces disease specific mortality is now established but current screening practices are suboptimal. Improvements in the screening process have the potential to have an immense impact.

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