The risks of screening: data from the Nottingham randomised controlled trial of faecal occult blood screening for colorectal cancer. Colorectal cancer mortality: effectiveness of biennial screening for fecal occult blood. Yearly colonoscopy, liver CT, and chest radiography do not influence 5-year survival of colorectal cancer patients. Reducing mortality from colorectal cancer by screening for fecal occult blood. Minnesota Colon Cancer Control Study. Results of screening, rescreening, and follow-up in a prospective randomized study for detection of colorectal cancer by fecal occult blood testing. Results for 68,308 subjects. A randomized trial of aspirin to prevent colorectal adenomas in patients with previous colorectal cancer. Low-dose aspirin and incidence of colorectal tumors in a randomized trial.
To determine the harm that ensues from faecal occult blood (FOB) screening for colorectal cancer.
                150 251 people were randomly allocated either to receive biennial Haemoccult FOB tests (n =75 253) or not to be contacted (n=74 998). Study group patients returning positive tests were offered colonic investigation; 1774 underwent complete investigation of the colon.
                There was no significant difference in the stage at presentation of interval versus control group cancers. Survival in the interval cancer group was significantly prolonged compared with the control group. Sensitivity for colonoscopy or flexible sigmoidoscopy and double contrast barium enema (DCBE) was 96.7%. There were no complications of DCBE but seven (0.5%) complications of colonoscopy, of which six required surgical intervention. There were no colonoscopy related deaths. No patients without colorectal cancer died within 30 days of colonic investigation. Five patients died within 30 days of surgery for screen detected colorectal neoplasia and a further two died without having surgery. Six patients died after 30 days but within two years of surgery for screen detected benign adenomas or stage A cancers; in all cases the cause of death was not related to colorectal cancer.
                There was investigation related morbidity but no mortality and little to support overdiagnosis bias. The group returning falsely negative tests had a better outcome compared with the whole control group. There is a negative side to any screening programme but mortality reduction in this and other trials suggests that a national programme of colorectal cancer screening should be given consideration. In 1993, a randomized controlled trial in Minnesota showed, after 13 years of follow-up, that annual fecal occult blood testing was effective in reducing colorectal cancer mortality by at least 33%. Biennial screening (i.e., every 2 years) resulted in only a 6% mortality reduction. Two European trials (in England and in Denmark) subsequently showed statistically significant 15% and 18% mortality reductions with biennial screening. Herein, we provide updated results-through 18 years of follow-up--from the Minnesota trial that address the apparent inconsistent findings among the trials regarding biennial screening.
                From 1976 through 1977, a total of 46551 study subjects, aged 50-80 years, were recruited and randomly assigned to an annual screen, a biennial screen, or a control group. A screen consisted of six guaiac-impregnated fecal occult blood tests (Hemoccult) prepared in pairs from each of three consecutive fecal samples. Participants with at least one of the six tests that were positive were invited for a diagnostic examination that included colonoscopy. All participants were followed annually to ascertain incident colorectal cancers and deaths.
                The numbers of deaths from all causes were similar among the three study groups. Cumulative 18-year colorectal cancer mortality was 33% lower in the annual group than in the control group (rate ratio, 0.67; 95% confidence interval [CI] = 0.51-0.83). The biennial group had a 21% lower colorectal cancer mortality rate than the control group (rate ratio, 0.79; 95% CI = 0.62-0.97). A marked reduction was also noted in the incidence of Dukes' stage D cancers in both screened groups in comparison with the control group.
                The results from this study, together with the other two published randomized trials of fecal occult blood screening, are consistent in demonstrating a substantial, statistically significant reduction in colorectal cancer mortality from biennial screening. Guidelines on the type and frequency of follow-up of patients after curative surgery for colorectal cancer are unclear. The aim of this study was to determine the survival benefit of a planned follow-up program.
                Three hundred twenty-five patients who underwent curative resection of colorectal cancer were prospectively randomized to either intensive or standard follow-up. After stratification according to Dukes' stage and site in the colon or rectum, patients were randomized to intensive follow-up of yearly colonoscopy, computerized tomography (CT) of the liver, and chest radiography and clinical review and simple screening vs. structured clinical review and simple screening tests only.
                On completion of 5-year follow-up, there was no significant difference in survival between the two groups. Yearly colonoscopy failed to detect any asymptomatic local recurrences. Only one asymptomatic curable metachronous colon tumor was detected. Liver CT resulted in earlier detection of hepatic metastases but did not increase the number of curative hepatectomies. Only 1 patient had an asymptomatic CT-detected liver metastasis, and another had an asymptomatic chest radiography-detected lung metastasis. Both had curative resections.
                Yearly colonoscopy, liver CT, and chest radiography will not improve survival from colorectal cancer when added to symptom and simple screening review. Although tests for occult blood in the feces are widely used to screen for colorectal cancers, there is no conclusive evidence that they reduce mortality from this cause. We evaluated a fecal occult-blood test in a randomized trial and documented its effectiveness.
                We randomly assigned 46,551 participants 50 to 80 years of age to screening for colorectal cancer once a year, to screening every two years, or to a control group. Participants who were screened submitted six guaiac-impregnated paper slides with two smears from each of three consecutive stools. About 83 percent of the slides were rehydrated. Participants who tested positive underwent a diagnostic evaluation that included colonoscopy. Vital status was ascertained for all study participants during 13 years of follow-up. A committee determined causes of death. A single pathologist determined the stage of each tissue specimen. Differences in mortality from colorectal cancer, the primary study end point, were monitored with the sequential log-rank statistic.
                The 13-year cumulative mortality per 1000 from colorectal cancer was 5.88 in the annually screened group (95 percent confidence interval, 4.61 to 7.15), 8.33 in the biennially screened group (95 percent confidence interval, 6.82 to 9.84), and 8.83 in the control group (95 percent confidence interval, 7.26 to 10.40). The rate in the annually screened group, but not in the biennially screened group, was significantly lower than that in the control group. Reduced mortality in the annually screened group was accompanied by improved survival in those with colorectal cancer and a shift to detection at an earlier stage of cancer.
                Annual fecal occult-blood testing with rehydration of the samples decreased the 13-year cumulative mortality from colorectal cancer by 33 percent. All 68,308 inhabitants of Göteborg born between 1918 and 1931 were randomly divided into a test and a control group. The subjects in the test group were invited to perform Hemoccult II fecal occult blood testing on 3 days and to repeat the test after 16 to 24 months. In the prevalence screening 21,347 (63%) performed the test, and in the rescreening 19,991 (60%). Investigation of the 942 (4.4%) with positive tests in the prevalence screening showed 47 cancers and 129 subjects with adenomas > or = 1.0 cm. In the rescreening 5.1% had a positive test, and 34 cancers and 122 subjects with adenomas (> or = 1.0 cm) were found among those. Cancer had also been diagnosed in 19 subjects in the interval between the two screening occasions and in 15 subjects among the non-responders. Forty-four cancers had been diagnosed in the control group during the same period. Cancers detected by screening were at a less advanced stage than in the control group. It is too early to show any effect of screening on mortality from colorectal cancer. Experimental studies in animals and observational studies in humans suggest that regular aspirin use may decrease the risk of colorectal adenomas, the precursors to most colorectal cancers.
                We conducted a randomized, double-blind trial to determine the effect of aspirin on the incidence of colorectal adenomas. We randomly assigned 635 patients with previous colorectal cancer to receive either 325 mg of aspirin per day or placebo. We determined the proportion of patients with adenomas, the number of recurrent adenomas, and the time to the development of adenoma between randomization and subsequent colonoscopic examinations. Relative risks were adjusted for age, sex, cancer stage, the number of colonoscopic examinations, and the time to a first colonoscopy. The study was terminated early by an independent data and safety monitoring board when statistically significant results were reported during a planned interim analysis.
                A total of 517 randomized patients had at least one colonoscopic examination a median of 12.8 months after randomization. One or more adenomas were found in 17 percent of patients in the aspirin group and 27 percent of patients in the placebo group (P=0.004). The mean (+/-SD) number of adenomas was lower in the aspirin group than the placebo group (0.30+/-0.87 vs. 0.49+/-0.99, P=0.003 by the Wilcoxon test). The adjusted relative risk of any recurrent adenoma in the aspirin group, as compared with the placebo group, was 0.65 (95 percent confidence interval, 0.46 to 0.91). The time to the detection of a first adenoma was longer in the aspirin group than in the placebo group (hazard ratio for the detection of a new polyp, 0.64; 95 percent confidence interval, 0.43 to 0.94; P=0.022).
                Daily use of aspirin is associated with a significant reduction in the incidence of colorectal adenomas in patients with previous colorectal cancer.
                Copyright 2003 Massachusetts Medical Society Laboratory, clinical, and epidemiologic studies have recently suggested that regular use of aspirin can reduce colorectal cancer incidence or mortality. However, observational epidemiologic analyses have had limited opportunity to control for confounding bias or to specify aspirin doses used.
                Our purpose was to examine the relationship between regular use of low-dose aspirin and incidence of invasive and noninvasive colorectal tumors by utilizing data from the Physicians' Health Study, a randomized, double-blinded, placebo-controlled trial of aspirin and beta carotene. We also attempted to determine whether invasive cancers among aspirin users were associated with rectal bleeding and early stage at diagnosis.
                The Physicians' Health Study includes 22071 U.S. male physicians. The aspirin arm was terminated in 1988 after a mean follow-up of 5 years. Stage at diagnosis and signs and/or symptoms during presentation were abstracted from medical records. Cox proportional hazards models were used to estimate relative risk (RR), 95% confidence intervals (CIs), and the association between aspirin and bleeding. Differences between aspirin and placebo groups in tumor risk over time were visualized with Kaplan-Meier curves. We assessed the association between aspirin and stage at diagnosis with a Mann-Whitney rank sum statistic for non-parametric comparison of two ordinal distributions.
                The RR of developing colorectal cancer for aspirin compared with placebo was 1.15 (95% CI = 0.80-1.65). For in situ cancers and polyps, the RR was 0.86 (95% CI = 0.68-1.10). There was no significant trend for decreasing RR by year of follow-up for invasive cancers (P = .09) or noninvasive tumors (P = .96). Aspirin and placebo groups did not differ in stage or prevalence of rectal bleeding at diagnosis.
                Regular aspirin use, at a dose adequate for preventing myocardial infarction, was not associated with a substantial reduction in the incidence of colorectal cancer during 5 years of randomized treatment and follow-up. A small decrease in polyps in the aspirin group could not be reliably distinguished from a chance association. Our results suggest that among low-dose aspirin users, (a) colorectal cancer mortality is not likely to be reduced by earlier detection and (b) incidence is not likely to be increased due to aspirin-induced gastrointestinal bleeding.
                The potential for a benefit from higher doses of aspirin or longer duration of use should be addressed by more detailed observational epidemiologic studies and prevention trials with longer follow-up of randomized participants.
Benefits of screening include a modest reduction in colorectal cancer mortality, a possible reduction in cancer incidence through the detection and removal of colorectal adenomas, and potentially, the less invasive surgery that earlier treatment of colorectal cancers may involve.Harmful effects of screening include the psycho-social consequences of receiving a false-positive result, the potentially significant complications of colonoscopy or a false-negative result, the possibility of overdiagnosis (leading to unnecessary investigations or treatment) and the complications associated with treatment.