Evaluation of Flexible Sigmoidoscopy Screening as an Adjunct to the National FOBT Screening Programme in Scotland - A Random Evaluation

Screening for colorectal cancer is now being introduced in many countries worldwide, but there is still considerable uncertainty as to the ideal modality. Population based trials of guaiac faecal occult blood testing (gFOBT) have consistently demonstrated significant reductions in disease specific mortalities and three randomised population based trials of biennial gFOBT have demonstrated reductions in deaths from colorectal cancer of around 16%. As a result of these trials, a demonstration pilot was performed in the United Kingdom which has led to the introduction of gFOBT screening in all four countries of the United Kingdom.

However, gFOBT has significant limitations. It is clear that this form of screening is associated with a substantial interval cancer rate in the region of 50 %, indicating a severe deficiency in sensitivity for cancer. Furthermore, as it is now well established that the majority of colorectal cancers arise from pre-existing adenomas, it is important for any colorectal screening programme to detect adenomas in order to reduce the incidence of the disease as well as the associated mortality. Although gFOBT does detect some adenomas, the randomised studies have not demonstrated a reduction in colorectal cancer incidence with the exception of the Minnesota Study that used rehydrated gFOBT resulting in a high positivity rate and a large number of colonoscopies. It should be borne in mind however, that the newer faecal immunochemical tests (FIT), which, unlike gFOBT, are specific for human haemoglobin, perform better in terms of both cancer and adenoma detection.

It is also of interest that recent scrutiny of the interval cancer data from the Scottish demonstration pilot has clearly demonstrated that gFOBT screening tends to under-detect cancers in women when compared with men. In addition, it is relatively insensitive for rectal cancer when compared with colon cancer. Analysis of quantitative FIT data in our laboratory as part of an evaluation of FIT as a first line test in Scotland, has shown that the mean faecal haemoglobin concentration in women is lower than that in men, and that the cutoff value required for women to give a 2% positivity rate (similar to that achieved by the gFOBT currently in use in the UK) is less than half that for men. Thus, for gender at least, FIT will have the same limitations as gFOBT.

In a recent randomised trial carried out in 14 UK centres, a single flexible sigmoidoscopy (FS) between the ages of 55 and 65 years has been shown to bring about a significant reduction in colorectal cancer mortality. In addition, and most importantly, after a period of four years a significant reduction in colorectal cancer incidence was observed, presumably as a result of the routine removal of adenomas at FS. Interestingly, the reduction in incidence was restricted to left-sided cancers despite the fact that total colonoscopy was carried out in all those with a significant index lesion found at FS (5% of the screened population). FS does not suffer from low specificity since false positives do not occur, and there is independent evidence that it is more sensitive than a single gFOBT or FIT. In addition, FS is ideally suited to detecting rectal cancers and adenomas, and it is unlikely that there would be a gender difference in the sensitivity.

This landmark study (henceforth referred to as the "UK FS trial") was, however, an efficacy study since it was carried out in a population who had already indicated an interest in participating and, as a result, the uptake in those randomised to FS was an impressive 71%. This, however, leaves significant questions surrounding the introduction of FS screening, as it is not clear how it would perform as a population screening tool. Extrapolation of the results of the FS trial to the general population would suggest an uptake in the region of around 30% and although it is not clear what the uptake of FS would be in the Scottish population, data from the Glasgow centre that participated in the FS indicate a likely uptake of 24%. This compares with an overall uptake of around 60% in the current Scottish Bowel Screening Programme based on gFOBT.