A single examination of the lower colon and rectum using sigmoidoscopy, between the ages of 55 and 64 years, reduced colorectal cancer mortality by 43% in those screened and incidence by one third.

These are findings of a long-term UK study reported in an upcoming edition of The Lancet. The article was written by Professor Wendy Atkin, Imperial College London, UK, and Professor Jane Wardle, University College London, UK, and colleagues from the UK Flexible Sigmoidoscopy Trial Investigators. The trial was funded by the UK Medical Research Council, Cancer Research UK, The UK National Institute for Health Research, and KeyMed.

Colorectal cancer is the third most frequently diagnosed cancer worldwide, accounting for more than 1 million cases and 600 000 deaths every year. Survival is strongly related to stage at diagnosis, with survival rates of 90% for localised cases. Current screening methods using the faecal occult blood test, which detects early cases, reduce mortality by around 15%, and many countries have introduced screening programmes based on this test.

Most colorectal cancers arise from adenomas: predominantly symptomless growths that develop in 20–30% of the population. Two-thirds of colorectal cancers and adenomas are located in the rectum and sigmoid (lower) colon, which can be examined by flexible sigmoidoscopy. The authors of this study proposed that one flexible sigmoidoscopy screen undertaken between ages 55 and 64 years is a cost-effective and acceptable method to reduce colorectal cancer incidence and mortality. Their hypothesis is based on observations suggesting that most people who develop a distal colon cancer will have developed an adenoma by 60 years of age, and that removal of adenomas by sigmoidoscopy provides long-term protection against the development of distal colorectal cancer.

Recruitment and screening were started in November, 1994 and completed in March, 1999. The study took place in 14 UK centres: 11 in England, two in Wales, and one in Scotland. Baseline findings from the trial were published in 2002, and in this Article the authors report the results after a median of 11 years of follow-up.

Participants underwent flexible sigmoidoscopy with polypectomy for small polyps and referral for colonoscopy if there were polyps meeting any of the following high-risk criteria: 1 cm or larger; three or more adenomas; tubulovillous or villous histology; severe dysplasia or malignant disease; or 20 or more hyperplastic (benign) polyps above the distal rectum. Individuals who had no polyps or only low-risk polyps at flexible sigmoidoscopy were discharged. A total of 170,432 eligible men and women, who had indicated on a previous questionnaire that they would accept an invitation for screening, were randomly allocated to intervention (flexible sigmoidoscopy screening) or control groups. The primary outcome was the incidence of colorectal cancer, including prevalent cases detected at screening.

113,195 people were assigned to the control group and 57,237 to the intervention group, of whom 112,939 and 57,099, respectively, were included in the final analyses. 40,674 (71%) people underwent flexible sigmoidoscopy. During screening and median follow-up of 11 years, 2,524 participants were diagnosed with colorectal cancer (1818 in control group vs 706 in intervention group) and 20,543 died (13 768 vs 6775; 727 certified from colorectal cancer [538 vs 189]). In intention-to-treat analyses (which included people assigned to screening but who did not attend), colorectal cancer incidence in the intervention group was reduced by 23% and mortality by 31%. Incidence of distal colorectal cancer (rectum and lower colon) was reduced by 50%. Incidence of colorectal cancer in people attending screening (excluding non-attendees) was reduced by 33% and mortality by 43%. The numbers needed to be screened to prevent one colorectal cancer diagnosis or death, by the end of the study period, were 191 and 489, respectively.

The authors say: "After 11 years of follow-up, colorectal cancer incidence was reduced by a third and colorectal cancer mortality by more than 40% in those who underwent screening. Confining results to the rectum and sigmoid (lower) colon, incidence was reduced by half in those who were screened." Furthermore, they point out that 59% (126) of the 215 colorectal cancer cases that developed were detected at screening and very few cases were detected post screening—suggesting that screening has a lasting protective effect.

The researchers also add that results of previous case-control studies suggested that flexible sigmoidoscopy could reduce distal colon cancer incidence and mortality by around 70%. They say: "So far the cumulative reduction in people attending screening in our study is 50%. This lower value is most likely attributable to dominance of screen-detected prevalent cancers in the first four years of follow-up, and only after this point did a benefit in terms of incidence reduction become apparent. If incidence in the screened participants remains low during further follow-up, the magnitude of the incidence reduction will continue to increase."

While the study recorded no effect of screening on the upper or proximal colon, sigmoidoscopy does not examine the upper colon so this result could be expected. Only the 5% participants with high-risk polyps were referred for more complete colonoscopy examination.

The authors add: "Rates of all-cause mortality excluding colorectal cancer were slightly, although not significantly, reduced in the intervention compared with the control group. This reassuring finding suggests that the screening did not have unexpected harms."

They continue: "Economic analyses suggest that, with pre-existing assumptions, a once-only flexible sigmoidoscopy screen at age 55 or 60 years would be cost saving, largely because of the avoided costs of treatment resulting from the reduction in incidence... Our study population is representative in terms of risk of colorectal cancer and there is no reason to believe that the potential benefits of screening would differ in people who chose not to participate."

They conclude: "The results from our trial show that flexible sigmoidoscopy is a safe and practical test and, when offered only once to people between ages 55 and 64 years, confers a substantial and longlasting protection from colorectal cancer."

In an accompanying Comment, Professor David F Ransohoff, Department of Medicine and Epidemiology, University of North Carolina at Chapel Hill, NC, USA, says that although sigmoidoscopy screening is not perfectly protective, "the good news is that this size of benefit is large for any cancer screening test, certainly compared with mammography for breast cancer or assay of prostate-specific antigen for prostate cancer".

He adds: "Perhaps even greater reduction for screening sigmoidoscopy will be observed after more follow-up in the UK and Norwegian randomised trials, because long follow-up is needed to account for the 'prevalent (screen detected) colorectal cancers [that] dilute any incidence reducing effect of polypectomy', as well as to detect mortality reduction...More frequent endoscopy might lead to still greater reductions in colorectal cancer, as may be assessed in the US randomised trial of screening sigmoidoscopy repeated at 5 years. In 2010, the UK randomised study must be regarded as the most reliable evidence about the size of the reduction in colorectal cancer for 10 years after endoscopic examination of the left [lower] colon."


Source: The Lancet