EDITORIAL Case-Control Studies of Colorectal Cancer Mortality: Is the Case Made for Screening Sigmoidoscopy? Sam Shapiro*
1546
Downloaded from http://jnci.oxfordjournals.org/ at UCSF Library on April 26, 2015
In this issue of the Journal, Newcomb et al. (7) present their findings on the benefit of screening sigmoidoscopy in reducing mortality from colorectal cancer. With the publication of this report and the recent article by Selby et al. (2), we now have results from two studies in rapid succession with substantially the same conclusion: Screening sigmoidoscopy does indeed markedly reduce the risk of mortality from cancer of the rectum and distal colon. Both studies applied a case-control design to the experience in group-practice health maintenance organizations. The case subjects were members of the plan who died of colorectal cancer, and the control subjects (matched by age, sex, and duration of enrollment prior to diagnosis) were drawn from the remaining membership. Histories of screening sigmoidoscopy, fecal occult blood testing, and digital rectal examination were obtained from the medical records of the plans. In the Newcomb study, a flexible sigmoidoscope was used in a majority of the examinations; in the Selby study, a rigid sigmoidoscope was used in all instances. Screening in both studies was defined as testing in the absence of evidence of symptoms in the records. In the Newcomb study, the odds ratio (OR), based on the extent to which case subjects and control subjects differed in the frequency of having had one or more screening sigmoidoscopic examinations, was extremely low, 0.21 (adjusted for family history of colorectal cancer and use of the other two tests). Accordingly, this study observed that screening sigmoidoscopy conferred protection against colorectal cancer mortality for about 80% of those who had the examination. Only 66 patients who died of colorectal cancer and 196 matched control subjects were involved, however, and the 95% confidence interval of the OR is wide (0.08-0.52). The adjusted OR (an extraordinarily small value of 0.05) was statistically significant (P = .006) for mortality from cancers of the rectum and rectosigmoid, sites that are reachable with the types of sigmoidoscopes used. The OR (0.36) for mortality from cancer above this point was low but not significant.
The earlier study by Selby et al., which was severalfold larger, also showed a substantial reduction (adjusted OR, 0.41) in mortality from cancers of the rectum and distal colon following screening sigmoidoscopy and no difference at all in mortality from cancer beyond the reach of the rigid sigmoidoscope. Both studies reported no benefit from screening with either fecal occult blood testing or rectal examination, but in the case of fecal occult blood testing, this lack of benefit was dismissed because of limitations of the tests performed. How shall we interpret these results? Do we have, at last, case-control studies that effectively deal with the problem of bias, which commentators have identified as plaguing this methodology (3,4)7 And, is it a moot exercise to conduct randomized controlled trials, with their attendant difficulties and costs and the duration of many years before efficacy of screening sigmoidoscopy is determined? Case-control studies have been a significant source of data in the development of knowledge about risk factors for disease and have provided evidence on the efficacy of screening that is supportive of the results reported by randomized controlled trials. An outstanding example of the latter is the attention given to information from case-control studies in The Netherlands and Italy, which reinforces conclusions from the Health Insurance Plan of Greater New York and the Swedish two-county randomized controlled trials about establishing policies for breast cancer screening (5). The problems in applying the case-control methodology and reaching valid conclusions have been attributed mainly to (a) the difficulty of identifying an appropriate comparison group for the case subjects, (b) the retrospective nature of the information on covariables, and (c) selection biases among the case subjects or control subjects that remain uncontrolled even after taking into account personal characteristics and other confounding factors for which data may be available. In the Newcomb and Selby studies, the authors argue that these issues have been dealt with successfully. Case subjects and control subjects come from the same parent populations (members of the health maintenance organizations). In addition, information on screening sigmoidoscopy and covariables is obtained from medical records rather than through interviews with subjects or proxies (in the case of death), which require long periods of recall. However, health maintenance organizations, like other health insurance plans, experience significant turnover in their membership, the intensity of which may vary for those who have screening sigmoidoscopy and those who do not. When we consider the periods during which deaths from colorectal cancer occurred (17 years in the Selby study; 10 years in the Newcomb study), this point becomes important.
Received September 21, 1992; accepted September 21, 1992. •Correspondence to: Sam Shapiro, Acting Chair and Professor Emeritus, Department of Health Policy and Management, Johns Hopkins School of Hygiene and Public Health, Rm. 482, 624 North Broadway St., Baltimore, MD 21205.
Journal of the National Cancer Institute
Journal of the National Cancer Institute Monographs . . . Oncology Overviews ... These and other cancer-related publications will be available to you when you receive free Priority Announcements. Sign up now! Use the form below. D YeS, please put me on your free Priority Announcement List (N-569) to be notified when JNCI Monographs, Oncology Overviews, and other cancer-related publications are issued.
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Vol. 84, No. 20, October 21, 1992
EDITORIAL 1547
Downloaded from http://jnci.oxfordjournals.org/ at UCSF Library on April 26, 2015
Matching case subjects and control subjects for comparable underlie the ranking of the case-control methodology by the periods of enrollment prior to diagnosis does not necessarily U.S. Preventive Services Task Force (
1546
Downloaded from http://jnci.oxfordjournals.org/ at UCSF Library on April 26, 2015
In this issue of the Journal, Newcomb et al. (7) present their findings on the benefit of screening sigmoidoscopy in reducing mortality from colorectal cancer. With the publication of this report and the recent article by Selby et al. (2), we now have results from two studies in rapid succession with substantially the same conclusion: Screening sigmoidoscopy does indeed markedly reduce the risk of mortality from cancer of the rectum and distal colon. Both studies applied a case-control design to the experience in group-practice health maintenance organizations. The case subjects were members of the plan who died of colorectal cancer, and the control subjects (matched by age, sex, and duration of enrollment prior to diagnosis) were drawn from the remaining membership. Histories of screening sigmoidoscopy, fecal occult blood testing, and digital rectal examination were obtained from the medical records of the plans. In the Newcomb study, a flexible sigmoidoscope was used in a majority of the examinations; in the Selby study, a rigid sigmoidoscope was used in all instances. Screening in both studies was defined as testing in the absence of evidence of symptoms in the records. In the Newcomb study, the odds ratio (OR), based on the extent to which case subjects and control subjects differed in the frequency of having had one or more screening sigmoidoscopic examinations, was extremely low, 0.21 (adjusted for family history of colorectal cancer and use of the other two tests). Accordingly, this study observed that screening sigmoidoscopy conferred protection against colorectal cancer mortality for about 80% of those who had the examination. Only 66 patients who died of colorectal cancer and 196 matched control subjects were involved, however, and the 95% confidence interval of the OR is wide (0.08-0.52). The adjusted OR (an extraordinarily small value of 0.05) was statistically significant (P = .006) for mortality from cancers of the rectum and rectosigmoid, sites that are reachable with the types of sigmoidoscopes used. The OR (0.36) for mortality from cancer above this point was low but not significant.
The earlier study by Selby et al., which was severalfold larger, also showed a substantial reduction (adjusted OR, 0.41) in mortality from cancers of the rectum and distal colon following screening sigmoidoscopy and no difference at all in mortality from cancer beyond the reach of the rigid sigmoidoscope. Both studies reported no benefit from screening with either fecal occult blood testing or rectal examination, but in the case of fecal occult blood testing, this lack of benefit was dismissed because of limitations of the tests performed. How shall we interpret these results? Do we have, at last, case-control studies that effectively deal with the problem of bias, which commentators have identified as plaguing this methodology (3,4)7 And, is it a moot exercise to conduct randomized controlled trials, with their attendant difficulties and costs and the duration of many years before efficacy of screening sigmoidoscopy is determined? Case-control studies have been a significant source of data in the development of knowledge about risk factors for disease and have provided evidence on the efficacy of screening that is supportive of the results reported by randomized controlled trials. An outstanding example of the latter is the attention given to information from case-control studies in The Netherlands and Italy, which reinforces conclusions from the Health Insurance Plan of Greater New York and the Swedish two-county randomized controlled trials about establishing policies for breast cancer screening (5). The problems in applying the case-control methodology and reaching valid conclusions have been attributed mainly to (a) the difficulty of identifying an appropriate comparison group for the case subjects, (b) the retrospective nature of the information on covariables, and (c) selection biases among the case subjects or control subjects that remain uncontrolled even after taking into account personal characteristics and other confounding factors for which data may be available. In the Newcomb and Selby studies, the authors argue that these issues have been dealt with successfully. Case subjects and control subjects come from the same parent populations (members of the health maintenance organizations). In addition, information on screening sigmoidoscopy and covariables is obtained from medical records rather than through interviews with subjects or proxies (in the case of death), which require long periods of recall. However, health maintenance organizations, like other health insurance plans, experience significant turnover in their membership, the intensity of which may vary for those who have screening sigmoidoscopy and those who do not. When we consider the periods during which deaths from colorectal cancer occurred (17 years in the Selby study; 10 years in the Newcomb study), this point becomes important.
Received September 21, 1992; accepted September 21, 1992. •Correspondence to: Sam Shapiro, Acting Chair and Professor Emeritus, Department of Health Policy and Management, Johns Hopkins School of Hygiene and Public Health, Rm. 482, 624 North Broadway St., Baltimore, MD 21205.
Journal of the National Cancer Institute
Journal of the National Cancer Institute Monographs . . . Oncology Overviews ... These and other cancer-related publications will be available to you when you receive free Priority Announcements. Sign up now! Use the form below. D YeS, please put me on your free Priority Announcement List (N-569) to be notified when JNCI Monographs, Oncology Overviews, and other cancer-related publications are issued.
Name Organization Address
If you are located in the U.S., mail this form to: U.S. Government Printing Office Superintendent of Documents Mail Stop: SSOM Washington, DC 20401-9374
FAX: (202) 512-2165 If you are located outside the U.S., return this form to:
ICIC/NCI/NIH
City, State, Zip Code, or Country
Bldg.82,Room123 Bethesda, MD 20892 USA
FAX: (301)480-8105 PLEASE DO NOT COMPLETE THIS FORM IF YOU HAVE DONE SO PREVIOUSLY. THANK YOU.
Vol. 84, No. 20, October 21, 1992
EDITORIAL 1547
Downloaded from http://jnci.oxfordjournals.org/ at UCSF Library on April 26, 2015
Matching case subjects and control subjects for comparable underlie the ranking of the case-control methodology by the periods of enrollment prior to diagnosis does not necessarily U.S. Preventive Services Task Force (
