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      Effect of screening sigmoidoscopy and screening colonoscopy on colorectal cancer incidence and mortality: systematic review and meta-analysis of randomised controlled trials and observational studies

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          Abstract

          Objectives To review, summarise, and compare the evidence for effectiveness of screening sigmoidoscopy and screening colonoscopy in the prevention of colorectal cancer occurrence and deaths.

          Design Systematic review and meta-analysis of randomised controlled trials and observational studies.

          Data sources PubMed, Embase, and Web of Science. Two investigators independently extracted characteristics and results of identified studies and performed standardised quality ratings.

          Eligibility criteria Randomised controlled trials and observational studies in English on the impact of screening sigmoidoscopy and screening colonoscopy on colorectal cancer incidence and mortality in the general population at average risk.

          Results For screening sigmoidoscopy, four randomised controlled trials and 10 observational studies were identified that consistently found a major reduction in distal but not proximal colorectal cancer incidence and mortality. Summary estimates of reduction in distal colorectal cancer incidence and mortality were 31% (95% confidence intervals 26% to 37%) and 46% (33% to 57%) in intention to screen analysis, 42% (29% to 53%) and 61% (27% to 79%) in per protocol analysis of randomised controlled trials, and 64% (50% to 74%) and 66% (38% to 81%) in observational studies. For screening colonoscopy, evidence was restricted to six observational studies, the results of which suggest tentatively an even stronger reduction in distal colorectal cancer incidence and mortality, along with a significant reduction in mortality from cancer of the proximal colon. Indirect comparisons of results of observational studies on screening sigmoidoscopy and colonoscopy suggest a 40% to 60% lower risk of incident colorectal cancer and death from colorectal cancer after screening colonoscopy even though this incremental risk reduction was statistically significant for deaths from cancer of the proximal colon only.

          Conclusions Compelling and consistent evidence from randomised controlled trials and observational studies suggests that screening sigmoidoscopy and screening colonoscopy prevent most deaths from distal colorectal cancer. Observational studies suggest that colonoscopy compared with flexible sigmoidoscopy decreases mortality from cancer of the proximal colon. This added value should be examined in further research and weighed against the higher costs, discomfort, complication rates, capacities needed, and possible differences in compliance.

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          Most cited references 48

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          The results of direct and indirect treatment comparisons in meta-analysis of randomized controlled trials.

          When little or no data directly comparing two treatments are available, investigators often rely on indirect comparisons from studies testing the treatments against a control or placebo. One approach to indirect comparison is to pool findings from the active treatment arms of the original controlled trials. This approach offers no advantage over a comparison of observational study data and is prone to bias. We present an alternative model that evaluates the differences between treatment and placebo in two sets of clinical trials, and preserves the randomization of the originally assigned patient groups. We apply the method to data on sulphamethoxazole-trimethoprim or dapsone/pyrimethamine as prophylaxis against Pneumocystis carinii in HIV infected patients. The indirect comparison showed substantial increased benefit from the former (odds ratio 0.37, 95% CI 0.21 to 0.65), while direct comparisons from randomized trials suggests a much smaller difference (risk ratio 0.64, 95% CI 0.45 to 0.90; p-value for difference of effect = 0.11). Direct comparisons of treatments should be sought. When direct comparisons are unavailable, indirect comparison meta-analysis should evaluate the magnitude of treatment effects across studies, recognizing the limited strength of inference.
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            Association of colonoscopy and death from colorectal cancer.

            Colonoscopy is advocated for screening and prevention of colorectal cancer (CRC), but randomized trials supporting the benefit of this practice are not available. To evaluate the association between colonoscopy and CRC deaths. Population-based, case-control study. Ontario, Canada. Persons age 52 to 90 years who received a CRC diagnosis from January 1996 to December 2001 and died of CRC by December 2003. Five controls matched by age, sex, geographic location, and socioeconomic status were randomly selected for each case patient. Administrative claims data were used to detect exposure to any colonoscopy and complete colonoscopy (to the cecum) from January 1992 to an index date 6 months before diagnosis in each case patient and the same assigned date in matched controls. Exposures in case patients and controls were compared by using conditional logistic regression to control for comorbid conditions. Secondary analyses were done to see whether associations differed by site of primary CRC, age, or sex. 10 292 case patients and 51 460 controls were identified; 719 case patients (7.0%) and 5031 controls (9.8%) had undergone colonoscopy. Compared with controls, case patients were less likely to have undergone any attempted colonoscopy (adjusted conditional odds ratio [OR], 0.69 [95% CI, 0.63 to 0.74; P < 0.001]) or complete colonoscopy (adjusted conditional OR, 0.63 [CI, 0.57 to 0.69; P < 0.001]). Complete colonoscopy was strongly associated with fewer deaths from left-sided CRC (adjusted conditional OR, 0.33 [CI, 0.28 to 0.39]) but not from right-sided CRC (adjusted conditional OR, 0.99 [CI, 0.86 to 1.14]). Screening could not be differentiated from diagnostic procedures. In usual practice, colonoscopy is associated with fewer deaths from CRC. This association is primarily limited to deaths from cancer developing in the left side of the colon.
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              Protection from colorectal cancer after colonoscopy: a population-based, case-control study.

              Colonoscopy with detection and removal of adenomas is considered a powerful tool to reduce colorectal cancer (CRC) incidence. However, the degree of protection achievable in a population setting with high-quality colonoscopy resources remains to be quantified. To assess the association between previous colonoscopy and risk for CRC. Population-based case-control study. Rhine-Neckar region of Germany. A total of 1688 case patients with colorectal cancer and 1932 control participants aged 50 years or older. A detailed lifetime history of CRC risk factors and preventive factors, including history and results of previous colonoscopies, and of medical data obtained by self-reports and medical records. Odds ratios of CRC associated with colonoscopy in the preceding 10 years were estimated, after adjustment for sex, age, education level, participation in a general health screening examination, family history of CRC, smoking status, body mass index, and use of nonsteroidal anti-inflammatory drugs or hormone replacement therapy. Overall, colonoscopy in the preceding 10 years was associated with 77% lower risk for CRC. Adjusted odds ratios for any CRC, right-sided CRC, and left-sided CRC were 0.23 (95% CI, 0.19 to 0.27), 0.44 (CI, 0.35 to 0.55), and 0.16 (CI, 0.12 to 0.20), respectively. Strong risk reduction was observed for all cancer stages and all ages, except for right-sided cancer in persons aged 50 to 59 years. Risk reduction increased over the years in both the right and the left colon. The study was observational, with potential for residual confounding and selection bias. Colonoscopy with polypectomy can be associated with strongly reduced risk for CRC in the population setting. Aside from strong risk reduction with respect to left-sided CRC, risk reduction of more than 50% was also seen for right-sided colon cancer. German Research Council and German Federal Ministry of Education and Research.
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                Author and article information

                Contributors
                Role: professor of epidemiology
                Role: senior researcher in epidemiology
                Role: senior researcher in epidemiology
                Journal
                BMJ
                BMJ
                bmj
                BMJ : British Medical Journal
                BMJ Publishing Group Ltd.
                0959-8138
                1756-1833
                2014
                9 April 2014
                : 348
                Affiliations
                [1 ]Division of Clinical Epidemiology and Aging Research, German Cancer Research Center, INF 581, 69120 Heidelberg, Germany
                [2 ]German Cancer Consortium, Heidelberg, Germany
                [3 ]Institute of Medical Biometry and Informatics, University of Heidelberg, Heidelberg, Germany
                Author notes
                Correspondence to: h.brenner@ 123456dkfz.de
                Article
                breh016792
                10.1136/bmj.g2467
                3980789
                © Brenner et al 2014

                This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 3.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/3.0/.

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