Screening for CRC

It is possible to prevent many CRCs even though we do not know the exact cause of most CRC. One of the most powerful weapons is regular screening or testing. Regular CRC screening can, in many cases, prevent the neoplasm altogether. This is because polyps can be detected and removed before they have the chance to turn into cancer. Screening can also result in finding CRC early, when the disease is highly curable.

The observation that a particular cancer has a more favourable survival rate if diagnosed at an early stage (like CRC) is important, but is only one element in the decision matrix used to determine whether or not to offer cancer screening to an asymptomatic population [157-159]. In general, the following criteria should be met [160,161]:

1. The disease should be an important public health problem, as measured by incidence, mortality and other measures of disease burden.

2. The disease should have a detectable preclinical phase.

3. Treatment of disease detected before the onset of clinical symptoms should offer benefits compared with treatment after the onset of symptoms.

4. The screening test should meet acceptable levels of accuracy and cost.

5. The screening test and follow-up requirements should be acceptable to individuals at risk and to their healthcare providers.

6. Treatment or intervention that improves survival or quality of life (compared with not screening) should be available for patients with recognised disease.

7. Adequate staffing and facilities for recruitment, testing, diagnosis and follow-up, treatment and programme management should be available.

8. The resources allocated to the screening programme (including testing, diagnosis and treatment of patients diagnosed) should be economically balanced in relation to other healthcare priorities.

Screening measures decrease the mortality and incidence of CRC by detecting early disease (when it is highly curable) and removing precancerous lesions [162].

Research supports the benefits of screening. In 1993, the Minnesota Colon Cancer Control Study, a randomised controlled clinical trial, showed that after 13 years of follow-up, annual faecal occult blood testing (FOBT) reduced CRC mortality by at least 33%, a result that was statistically significant [163]. Subsequently, two European randomised trials, the Nottingham trial [164] and the Funen trial [165], have also found statistically significant CRC mortality reductions from biennial screening with Hemoccult.

Moreover, five case-control studies [166-170] have shown a reduction in the risk of dying from CRC using faecal occult blood screening or sigmoi-doscopy. A meta-analysis of six controlled trials using Hemoccult found a 16% reduction in CRC mortality (95% confidence interval (CI) 7-23%) [171] in the populations.

after FOBT, a significant reduction has also been demonstrated, not only in mortality, but also in the incidence of CRC. The most plausible explanation is the identification and removal of the precursor lesions for CRC (adenomatous polyps) [172]. Combining FOBT with flexible sigmoidoscopy could further reduce mortality.

A sigmoidoscopy may discover many adenomas and early cancers that do not bleed and FOBT confers some added protection against proximal tumours unaccompanied by distal marker lesions discoverable at the time of a sigmoidoscopy. However, this added benefit may be quite small. Empirical studies are needed to establish and quantify any benefit and to determine if the combination is cost-effective and acceptable to patients.

Evidence for the effectiveness of the other approaches, colonoscopy and double-contrast barium enema (DCBE), is less direct and rests primarily on the studies of FOBT and sigmoidoscopy. Given the relative length of the instruments, it is not surprising that colonoscopy is more sensitive than sig-moidoscopy [173, 174]. It seems highly plausible to extrapolate the proven benefits of sigmoidoscopy to the entire colon for colonoscopy, particularly when results of the three FOBT trials are considered (studies designed on the assumption that colonoscopic screening could lower CRC mortality rates). The goal of FOBT is simply to make colonoscopic screening more efficient by identifying those most likely to benefit.

The evidence for DCBE is limited to descriptive studies showing that it has a relatively high sensitivity (50-94%) when compared with endoscopy for cancer and larger adenomatous polyps [175,176]. Compared with FOBT, DCBE's sensitivity is much higher for adenomas and at least as high for cancer. It therefore seems plausible that screening with DCBE may also provide benefit when positive results are followed up with endoscopic polypectomy or surgery.

Although there is a general consensus concerning the efficacy of CRC screening [163-165, 173-179], there is a lack of agreement about which routine screening strategy should be adopted.

In Italy, a multicentre, randomised trial was conducted from November 1999 through June 2001 among a sample of 55-64 years olds in the general population who had an average risk of CRC, to evaluate patient compliance to different screening strategies [180]. The eligible subjects were randomly assigned to: (1) biennial FOBT (delivered by mail); (2) biennial FOBT (delivered by general practitioner or a screening facility); (3) patient's choice of FOBT or "once-only" sigmoidoscopy; (4) "once-only" sigmoidoscopy; or (5) sigmoidoscopy followed by biennial FOBT.

The participation rates for groups 1, 2, 3, 4 and 5 were 30.1% (682/2266), 28.1% (1654/5893), 27.1% (970/3579), 28.1% (1026/3650) and 28.1% (3049/10 867), respectively. Of the 2858 subjects screened by FOBT, 4.3% had a positive test result, 10 (3.5 per 1000) had CRC and 39 (1.4%) had an advanced adenoma. Among the 4466 subjects screened by sigmoi-doscopy, 341 (7.6%) were referred for colonoscopy, 18 (4 per 1000) had CRC and 229 (5.1%) harboured an advanced adenoma. Segnan et al. concluded their studying saying that the participation rates were similar for sigmoidoscopy and FOBT, and, the detection rate for advanced neoplasia was three times higher following screening by sigmoidoscopy than by FOBT [180].

Perspectives on screening must concern new techniques of imaging and new analytical approaches.

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