Abstract Haemoccult®, a guaiac test for faecal occult blood, detects 56–78 per cent of asymptomatic carcinomas when performed over 3 days. In patients with known colorectal cancer the sensitivity of the test for neoplasia is increased by extending the test period to 6 days. We report the first randomized comparison of 3 day with 6 day testing in asymptomatic individuals. 35184 age and sex matched individuals were randomly allocated to receive Haemoccult over 3 or 6 days. The tests were completed by 10176 (57·8 per cent) of the 17616 offered 3 day Haemoccult and 9461 (53·9 per cent) of the 17568 offered 6 day Haemoccult, a significant decrease in compliance (P<0·001). Of the 3 day Haemoccult tests 131 (1·29 per cent) were positive, significantly fewer than the 160 (1·69 per cent) positive tests after 6 day Haemoccult (0·01 < P < 0·02). Investigation of subjects with a positive test revealed 20 carcinomas (1·14 per 1000 offered and 1·97 per 1000 completing the test) in the 3 day group and 24 carcinomas (1·37 per 1000 offered and 2·54 per 1000 completing the test) after 6 day Haemoccult tests (0·5<P<0·7 for those offered the test and 0·3<P<0·5 for those completing it). After 3 day Haemoccult 112 adenomas in 76 persons were detected (4·31 per 1000 offered and 7·47 per 1000 completing the test). In the 6 day group 123 adenomas in 83 persons (4·72 per 1000 offered and 8·77 per 1000 completing the test) were detected (0·5 < P < 0·7 for those offered the test and 0·3 < P < 0·5 for those completing it). Large adenomas were found in 27 individuals after 3 day testing (1·53 per 1000 offered the test and 2·65 per 1000 completing it) and in 35 individuals after 6 day testing (1·99 per 1000 offered the test and 3·70 per 1000 completing it) (0·3<P<0·5 for those offered the test and 0·l<P<0·2 for those completing it). This study has not demonstrated a significant increase in the yield of neoplasia in asymptomatic subjects offered Haemoccult over 6 days. However there was a significant decrease in compliance and a higher rate of colonoscopy in those offered 6 day testing.
Three large randomised trials have shown that screening for colorectal cancer (CRC) using the faecal occult blood test (FOBt) can reduce the mortality from this disease. The largest of these trials, conducted in Nottingham since 1981, randomised 152 850 individuals between the ages of 45 and 74 years to an intervention arm receiving biennial Haemoccult (FOB) test kit or to a control arm. In 2006, the National Bowel Cancer Screening Programme was launched in England using the FOBt, with the expectation that it will reduce CRC mortality.
Aims
To compare the CRC mortality and incidence in the intervention arm with the control arm after long-term follow-up.
Methods
The 152 850 randomised individuals were followed up through local health records and central flagging (Office for National Statistics).
Results
At a median follow-up of 19.5 years there was a 13% reduction in CRC mortality (95% CI 3% to 22%) in the intervention arm despite an uptake at first invitation of approximately 57%. The CRC mortality reduction in those accepting the first screening test, adjusted for the rate of non-compliers, was 18%. There was no significant difference in mortality from causes other than CRC between the intervention and control arms. Despite removing 615 adenomas >10 mm in size from the intervention arm, there was no significant difference in CRC incidence between the two arms.
Conclusions
Although the reduction in CRC mortality was sustained, further follow-up of the screened population has not shown a significant reduction in the CRC incidence. Moreover, despite the removal of many large adenomas there was no reduction in the incidence of invasive cancer which was independent of sex and site of the tumour.
To determine the harm that ensues from faecal occult blood (FOB) screening for colorectal cancer.
METHODS
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.
RESULTS
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.
CONCLUSIONS
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.
Cause specific mortality statistics derived from death certificates are highly dependent upon the accuracy of certification by the attending physician. In the Nottingham colorectal cancer screening trial, there were 12 624 deaths among the screening group and 12 515 among the control group during the period under consideration. There was no significant difference in all cause mortality rate (excluding deaths due to colorectal cancer) between the two study groups (rate ratio = 1.01, 95% confidence interval = 0.99 to 1.03). Disease specific mortality rates did not differ significantly between the two groups either. Overall, the agreement between verified and certified cause of death was 86%. Using the certified cause of death would have resulted in an underestimation bias of 6.27% for colorectal cancer deaths.
Abstract A study was carried out to investigate the change in stage at presentation of patients with colorectal cancer over 10 years. Cases were identified from the control group of subjects enrolled into a randomized controlled study based on Haemoccult screening for colorectal neoplasia. Of 405 subjects in the control group presenting with symptomatic colorectal cancer, 206 presented before 1989 and 199 since then. The number of patients with Dukes' stage A carcinoma diagnosed since 1989 rose from 21 (10·4 per cent) to 35 (18·1 per cent); this change occurred for rectosigmoid tumours (9·9 per cent before 1989, 28 per cent after 1989) but not for colonic cancer (10·9 per cent before 1989, 11·5 percent thereafter). An increase in the proportion of patients with symptomatic early-stage rectosigmoid cancer has been observed in the past 10 years. No such change occurred in those with colonic cancer. This may reflect a change in awareness of the disease and its symptoms by patients and general practitioners.
To report the causes of, and ages at, death of subjects in an English colorectal cancer screening trial.
Design and setting
Analysis of 78 708 deaths occurring between 1981 and 2008, within the Nottingham randomised controlled trial of biennial faecal occult blood testing.
Main outcome measures
Cause of death, age at death by sex and by cause.
Results
Significantly more subjects died from verified colorectal cancer in the trial9s control group than in the intervention group (3.2% vs 2.9%). For no other major cause of death was the difference in proportion across the two groups statistically significant. Age at death was lower for cancer than for other principal causes, except for ischaemic heart disease among women. However, mean age at death was higher for colorectal cancer than for other cancers, except for prostate cancer among men. Increasing levels of material deprivation significantly lowered the expected ages at death, independently of cause. For both men and women, the mean age at death from all causes for screening participants was higher than that of controls and non-participants. Mean deprivation was lowest among participants. Of those participating in screening, and dying from colorectal cancer, subjects receiving negative test results lived significantly longer than those who received positive test results. However, if dying from other causes, they died at an earlier age.
Conclusions
The age at death from colorectal cancer is higher than that of most other cancers. Those accepting a screening invitation live longer than non-participants. In part, this difference is explained by relative deprivation. Among screening participants, the receipt of a positive, as opposed to a negative, test result is associated with a later age at death.
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