BACKGROUND

The third millennium is witnessing the emergence of preventive medicine as a cornerstone in our concept of health. Colorectal cancer (CRC) is a major health concern (Chapter 17), and one that fits the criteria of a preventable disease. Approximately two-thirds of the cases involve average-risk men and women, with a sharp increase of its incidence starting from the fifth decade of life.

Detection and removal of colonic adenomas, the non-invasive neoplasm that are the precursors of CRC, could prevent up to 90% of CRC cases. The transition process between adenomas to carcinoma is estimated as 5–10 years and that of normal mucosa thorough adenoma to adenocarcinoma as 15–20 years. This interval provides a unique window of opportunity for screening and effective interventions to reduce CRC-associated mortality. The respective curative benefits that can be gained by detecting CRC at early stages, e.g. node-negative stages I and II, are as high as 90% and 75%, respectively, with surgery alone, while the 5-year survival rate is close to zero for metastatic CRC.

Most medical societies strongly recommend mass screening of the average-risk adult population starting at age 50 and earlier for individuals at higher risk due to family history or other predisposing factors. Several screening tests are available and are in common use.

FAECAL OCCULT BLOOD TESTING

Faecal occult blood test (FOBT) is a low-cost, non-invasive periodic procedure that detects faecal haemoglobin and does not require cathartic bowel preparation. Currently available approaches include a guaiac test, based on the peroxidase-like activity of haemoglobin, or immunochemical analysis. In the guaiac-based assay, accuracy of FOBT may be affected by stool re-hydration (which increases sensitivity but decreases specificity), haem degradation (reduced sensitivity), medications (false positives with non-steroidal antiinflammatory drugs [NSAIDS] and false negatives with vitamin C) and interfering dietary ingredients (such as peroxidases and meat haem). Recent professional guidelines have suggested that re-hydration is not recommended since the readability of the test is unpredictable, and the false positive rate is substantially increased. Newer guaiac-based and immunochemical tests are now available with improved sensitivity.

Support for the ability of annual FOBT to reduce the mortality from CRC emerged from several large prospective randomised trials. Mortality was reduced by 15%–33% if the test was done yearly, and when positive results were followed by colonoscopy. A meta-analysis that pooled the results of these studies estimated a 16%–23% reduction in CRC mortality. The estimated FOBT sensitivity for cancer ranges between 30% and 90% depending upon the test used. The major limitation of FOBT is its low sensitivity as a screening test, since some carcinomas and most adenomas do not bleed. Only 24% of advanced neoplasia cases had a positive FOBT result on the three consecutive days’ samples obtained prior to bowel preparation. Proper FOBT testing requires examining three different bowel movements. Prerequisite compliance is difficult to achieve from both patients and physicians. In addition, the test gives an indirect result; hence, individuals who test positive have to undergo colonoscopy to confirm the presence of polyps, cancer or other pathology. Survival benefit may therefore reflect the benefit of colonoscopy, for detecting incidental lesions including those of subjects with false positive FOBT results. Lastly, upper gastrointestinal (GI) tract sources of occult bleeding, NSAID use or false positive results due to dietary ingredients may lead to unnecessary colonoscopies. There is often a low referral rate of patients with positive FOBT screening findings.

FOBT testing has no merit as a single test. It should definitely not be done when a patient has overt rectal bleeding (see Chapter 20) or any alarm symptoms. In such cases colonoscopy must be performed.

SIGMOIDOSCOPY

This method provides direct endoscopic visualisation of the distal part of the colon, preferably up to the splenic flexure, and enables biopsies to be taken and polyps resected. Sigmoidoscopy is considered less invasive than colonoscopy and requires a simple bowel preparation of only two fleet enemas, one hour prior to the procedure. It usually does not require sedation and can be performed by trained nurses. A finding of a neoplastic/dysplastic lesion mandates full evaluation of the entire large intestine by colonoscopy although, according to some guidelines, this decision should be individualised and be performed in high-risk subjects (e.g. age ≥65 years, villous histology in the large adenoma ≥1 cm or multiple adenomas). The currently published data on reducing CRC mortality by screening sigmoidoscopy are derived from non-prospective case-controlled trials which report that screening sigmoidoscopy can reduce the incidence and death rates of distal CRC by 59%–80% and lower overall CRC mortality by up to 40%–50%.

The main drawback of sigmoidoscopy is the limit of its extension, which is up to the splenic flexure at best. Unfortunately, the distance is often significantly shorter. Sensitivity actually depends on the varied experience of the examiners, and on patient discomfort, two factors that have a major impact on the depth of insertion and adequacy of mucosal inspection. Even in the hands of expert endoscopists, the sigmoidoscope was found to traverse the sigmoid colon in only 66% of cases. For more than 50% of proximal advanced lesions (i.e. advanced adenoma or carcinoma) there were no lesions in the distal colon, so those would have been missed by sigmoidoscopy. Sigmoidoscopy is even less rewarding in subjects aged 65–75 years, as a proximal shift of neoplasia in this age group is suggested.

COMBINED FOBT AND SIGMOIDOSCOPY

There is a lack of prospective data regarding the value of a combined approach of 5-year sigmoidoscopy and annual FOBT. Some evidence suggests that it may possess some advantage, as sigmoidoscopy is intended to screen the distal colon, and FOBT is more effective in detecting proximal lesions. Supporting data from case-control studies report that screening FOBT and sigmoidoscopy are individually associated with reduced CRC mortality after controlling for the other test. When both tests are to be done, the FOBT should be performed first because a positive result is an indication for colonoscopy, obviating the need for sigmoidoscopy. This combination may improve the relative efficacy of each test alone, and has been suggested as an alternative strategy for screening colonoscopy. The limitation of this combined approach is exposing individuals to inconvenience, cost and complications of both FOBT and sigmoidoscopy with an uncertain gain in efficacy.

COLONOSCOPY

Colonoscopy is the gold standard procedure to identify colorectal neoplasia. Skilled gastroenterologists perform the examination after a cathartic bowel preparation. Using back-to-back colonoscopies, it was shown that the sensitivity of a single colonoscopy is about 90%–95% for cancers and large adenomas and 75% for polyps <1 cm. The detection rates for adenomas ≥10 mm, 5–10 mm and 1–5 mm were found to be 98%, 87% and 74%, respectively. Colonoscopy miss rates are related to the skills of the endoscopist, withdrawal technique and, in particular, withdrawal time that reflects the time spent to inspect the colon. Although there are no published prospective studies on direct reduction of CRC mortality by primary screening colonoscopy, there is a large body of evidence to support it. The National Polyp Study has demonstrated a 76%–90% decrease in the incidence of CRC at 6 years after the index colonoscopy and polypectomy, compared with several appropriately selected control groups. A prospective 13-year follow-up demonstrated a relative risk of 0.2 for CRC in subjects who underwent colonoscopy with polyp removal compared with the control group. The prevalence of CRC in asymptomatic patients being screened aged 50–75 years in the USA is approximately 1%. Overall, the findings support the use of colonoscopy rather than sigmoidoscopy for screening in this age group.

The bowel preparation is inconvenient and poses a major obstacle. The myths of the discomfort of colonoscopy may be unjustified, since the examination is performed under conscious sedation and discomfort is rare. Indeed, patients who have undergone both endoscopic examinations report that non-sedated sigmoidoscopy is associated with a significantly higher recalled level of discomfort compared with conscious sedated colonoscopy. Studies on colonoscopy in the setting of ambulatory screening examinations have shown a considerably low risk of morbidity (0.1%–0.3%) with no procedure-related deaths. Colonoscopy costs more than FOBT and sigmoidoscopy. The true calculations, however, should be based on the long-term costs for a life-year saved. In a realistic model of a <50% compliance rate, the estimated cost per death prevented was similar for FOBT and endoscopy. Furthermore, if colonoscopy costs are below $750, once-in-a-life-time colonoscopy was found to be more cost effective than any other screening modality at every level of compliance.