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      Long-Term Mortality after Screening for Colorectal Cancer

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          Abstract

          In randomized trials, fecal occult-blood testing reduces mortality from colorectal cancer. However, the duration of the benefit is unknown, as are the effects specific to age and sex. In the Minnesota Colon Cancer Control Study, 46,551 participants, 50 to 80 years of age, were randomly assigned to usual care (control) or to annual or biennial screening with fecal occult-blood testing. Screening was performed from 1976 through 1982 and from 1986 through 1992. We used the National Death Index to obtain updated information on the vital status of participants and to determine causes of death through 2008. Through 30 years of follow-up, 33,020 participants (70.9%) died. A total of 732 deaths were attributed to colorectal cancer: 200 of the 11,072 deaths (1.8%) in the annual-screening group, 237 of the 11,004 deaths (2.2%) in the biennial-screening group, and 295 of the 10,944 deaths (2.7%) in the control group. Screening reduced colorectal-cancer mortality (relative risk with annual screening, 0.68; 95% confidence interval [CI], 0.56 to 0.82; relative risk with biennial screening, 0.78; 95% CI, 0.65 to 0.93) through 30 years of follow-up. No reduction was observed in all-cause mortality (relative risk with annual screening, 1.00; 95% CI, 0.99 to 1.01; relative risk with biennial screening, 0.99; 95% CI, 0.98 to 1.01). The reduction in colorectal-cancer mortality was larger for men than for women in the biennial-screening group (P=0.04 for interaction). The effect of screening with fecal occult-blood testing on colorectal-cancer mortality persists after 30 years but does not influence all-cause mortality. The sustained reduction in colorectal-cancer mortality supports the effect of polypectomy. (Funded by the Veterans Affairs Merit Review Award Program and others.).

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          Most cited references 28

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          Nonparametric Estimation from Incomplete Observations

           E. Kaplan,  Paul Meier (1958)
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            Colonoscopic polypectomy and long-term prevention of colorectal-cancer deaths.

            In the National Polyp Study (NPS), colorectal cancer was prevented by colonoscopic removal of adenomatous polyps. We evaluated the long-term effect of colonoscopic polypectomy in a study on mortality from colorectal cancer. We included in this analysis all patients prospectively referred for initial colonoscopy (between 1980 and 1990) at NPS clinical centers who had polyps (adenomas and nonadenomas). The National Death Index was used to identify deaths and to determine the cause of death; follow-up time was as long as 23 years. Mortality from colorectal cancer among patients with adenomas removed was compared with the expected incidence-based mortality from colorectal cancer in the general population, as estimated from the Surveillance Epidemiology and End Results (SEER) Program, and with the observed mortality from colorectal cancer among patients with nonadenomatous polyps (internal control group). Among 2602 patients who had adenomas removed during participation in the study, after a median of 15.8 years, 1246 patients had died from any cause and 12 had died from colorectal cancer. Given an estimated 25.4 expected deaths from colorectal cancer in the general population, the standardized incidence-based mortality ratio was 0.47 (95% confidence interval [CI], 0.26 to 0.80) with colonoscopic polypectomy, suggesting a 53% reduction in mortality. Mortality from colorectal cancer was similar among patients with adenomas and those with nonadenomatous polyps during the first 10 years after polypectomy (relative risk, 1.2; 95% CI, 0.1 to 10.6). These findings support the hypothesis that colonoscopic removal of adenomatous polyps prevents death from colorectal cancer. (Funded by the National Cancer Institute and others.).
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              Randomised controlled trial of faecal-occult-blood screening for colorectal cancer.

              There is growing evidence that faecal-occult-blood (FOB) screening may reduce colorectal cancer (CRC) mortality, but this reduction in CRC mortality has not been shown in an unselected population-based randomised controlled trial. The aim of this study was to assess the effect of FOB screening on CRC mortality in such a setting. Between February, 1981, and January, 1991, 152,850 people aged 45-74 years who lived in the Nottingham area of the UK were recruited to our study. Participants were randomly allocated FOB screening (76,466) or no screening (controls; 76,384). Controls were not told about the study and received no intervention. Screening-group participants were sent a Haemoccult FOB test kit with instructions from their family doctor. FOB tests were not rehydrated and dietary restrictions were imposed only for retesting borderline results. Individuals with negative FOB tests at the first screening, together with those who tested positive but in whom no neoplasia was found on colonoscopy, were invited to take part in further screening every 2 years. Screening was stopped in February, 1995, by which time screening-group participants had been offered FOB tests between three and six times. Screening-group participants who had a positive test were offered full colonoscopy. All participants were followed up until June, 1995. The primary outcome measure was CRC mortality. Of the 152,850 individuals recruited to the study, 2599 could not be traced or had emigrated and were excluded from the analysis. Thus, there were 75,253 participants in the screening group and 74,998 controls. 44,838 (59.6%) screening-group participants completed at least one screening. 28,720 (38.2%) of these individuals completed all the FOB tests they were offered and 16,118 (21.4%) completed at least one screening but not all the tests they were offered. 30,415 (40.4%) did not complete any test. Of 893 cancers (20% stage A) diagnosed in screening-group participants (CRC incidence of 1.49 per 1000 person-years), 236 (26.4%) were detected by FOB screening, 249 (27.9%) presented after a negative FOB test or investigation, and 400 (44.8%) presented in non-responders. The incidence of cancer in the control group (856 cases, 11% stage A) was 1.44 per 1000 person-years. Median follow-up was 7.8 years (range 4.5-14.5). 360 people died from CRC in the screening group compared with 420 in the control group-a 15% reduction in cumulative CRC mortality in the screening group (odds ratio=0.85 [95%; CI 0.74-0.98], p = 0.026). Our findings together with evidence from other trials suggest that consideration should be given to a national programme of FOB screening to reduce CRC mortality in the general population.
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                Author and article information

                Journal
                New England Journal of Medicine
                N Engl J Med
                Massachusetts Medical Society
                0028-4793
                1533-4406
                September 19 2013
                September 19 2013
                : 369
                : 12
                : 1106-1114
                Article
                10.1056/NEJMoa1300720
                24047060
                © 2013
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