Li Ka Shing Knowledge Institute, St Michael's Hospital, University Health Network, University of Toronto, Toronto, Ontario, Canada. baxtern@smh.toronto.on.ca
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
The main purpose of population screening for colorectal cancer is to reduce mortality from the disease. The criteria of death from colorectal cancer are defined in the present randomized trial of 61,938 persons between 45 and 74 years old, and the need for an impartial death review committee was demonstrated. Causes of death within the first 5 years are described within subgroups of the test group and compared with those in the control group. Death rates were higher among non-responders to screening than among controls and among those in whom Hemoccult-II had been performed at least once. Persons with negative Hemoccult-II had a lower death rate than controls. The overall autopsy rate was 32%. Lethal complications from treatment of colorectal neoplasia were evaluated per se. Death from colorectal cancer occurred in 74 persons in the total screening group and in 91 among controls. Sources of bias are discussed. A method of evaluating possible benefit to those being screened is suggested. Final results cannot be expected before 1996.
Colorectal cancers (CRCs) diagnosed relatively soon after a colonoscopy are referred to as interval CRCs. It is not clear whether interval CRCs arise from prevalent lesions missed at colonoscopy or represent specific aggressive biology leading to poor survival.
Using Danish population-based medical registries (2000-2009), we investigated patients with "interval" CRC diagnosed within 1-5 years of a colonoscopy, and compared them with cases with colonoscopy =10 years before diagnosis and to "sporadic" CRCs with no colonoscopy before diagnosis. Multivariate logistic regression was used to explore the association between clinical, demographic, and comorbidity characteristics and interval CRC. We assessed survival using Kaplan-Meier methods and mortality rate ratios (MRRs) using Cox regression, adjusting for covariates including the Charlson Comorbidity Index (CCI 0, 1-2, 3+).
The comparison of the 982 interval CRCs to the 358 patients with CRC =10 years after colonoscopy revealed nearly similar characteristics and mortality. In the comparison with the 35,704 sporadic CRCs, interval cases were slightly older (74 vs. 71 years), more likely to be female (54 vs. 48%), have comorbidities (CCI3+: 28 vs. 15%), have proximal tumors (38 vs. 22%), and tumors with mucinous histology (9.1 vs. 7.0%), but stage was similar (metastatic 23 vs. 24%). In logistic regression analysis, female sex, localized stage at diagnosis, proximal tumor location, and high comorbidity burden were factors independently associated with interval CRC. The 1-year survival was 68% (95% confidence interval (CI): 65%, 71%) in interval and 71% (95% CI: 70%, 71%) in sporadic cases, with an adjusted MRR of 0.92 (95% CI 0.82, 1.0). After 5 years, survival was 41% (95% CI: 37%, 44%) in interval and 43% (95% CI: 42%, 43%) in sporadic cases, and the adjusted 2-5 year MRR was 1.0 (95% CI 0.88, 1.2).
Clinical characteristics and survival among interval CRCs did not suggest aggressive biology, but rather that the majority represented missed lesions.
Notes
Comment In: Am J Gastroenterol. 2013 Aug;108(8):1341-323912407
BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.
Notes
Comment In: J Natl Cancer Inst. 1999 Mar 3;91(5):399-40010070932
Comment In: J Natl Cancer Inst. 1999 Sep 1;91(17):150710469753
Colorectal cancer mortality can be reduced by repeated faecal occult blood (FOB) testing followed by colonoscopy for test positives. The object of this report is to describe how to launch a new screening programme in such a way that its effectiveness can be reliably evaluated. The programme is based on gradual expansion over time with individual-level randomization into screening or control arms among a target population aged 60-69 years in Finland. The target population will be sampled from the population register for invitees and controls by municipality and by birth cohort. The non-invited controls will gradually be screened only after the six-year implementation period. After 10 years, the programme covers the entire target population. The effects of screening will be evaluated, comparing the incidence of and mortality from colorectal cancer in those invited to screening with controls. The primary screening test is a biannual guaiac-based FOB test with three test cards for consecutive samples. In September-December 2004, around 5000 test-kits were sent to 22 piloting municipalities. In 2005, the programme expands both among municipalities and the target population, resulting in nearly 20,000 individual requests. The implementation of colorectal cancer screening in Finland in this way meets the criteria for a randomized controlled trial and the requirements for a public health programme. It allows unbiased research data to be collected while introducing the programme and may set an example for the introduction of all national screening programmes.
Population screening for colorectal cancer (CRC) using faecal occult blood test (FOBT) will be introduced in Denmark in 2014. Prior to the implementation of the screening programme, a feasibility study was performed in 2005-2006. In this paper, occurrences of colorectal cancer in the feasibility study cohort were reviewed with respect to the effect of screening participation on stages and survival.
All cases of CRC in a feasibility study cohort diagnosed from the beginning of the study until two years after the study ended were identified. Differences in the distribution of colon cancer stages and rectal cancer groups between the various screening categories were analysed through ?(2)-tests. Survival analysis with respect to screening groups was done by Kaplan-Meier and Cox-Mantel hazard ratios, and survival was corrected for lead time.
Colon cancers detected through screening were diagnosed at significantly lower stages than among screening non-responders. There were relatively fewer locally advanced rectal cancers among patients diagnosed through positive FOBT than among non-responders. Survival among screening cancer patients was superior to that of all other screening groups. No effect of lead time was detected. Neither stage nor survival among patients who had a negative FOBT was inferior to the unscreened Danish population.
The positive effect on survival among screening cancer patients is neither outbalanced by more advanced cancers among FOBT-negative patients than among non-responders nor by risks reported for colonoscopy.
