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Julia E C W Verne a ICRF Colorectal Cancer Unit,
St Mark's Hospital, Northwick Park, Middlesex HA1
3UJ, b Bridge Cottage Surgery,
Welwyn, Hertfordshire AL6 9EF, c ICRF Medical Statistics
Group, Centre for Statistics in Medicine, Institute of Health
Sciences, Oxford OX3 7LF, d Department of
Histopathology, St Mark's Hospital
Correspondence
to: Dr J E C W Verne, North Thames Regional Office, London W2 3QR
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Abstract |
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Objectives: To compare the feasibility of mass
screening by flexible sigmoidoscopy with screening by faecal occult
blood testing (Haemoccult) and both tests combined.
Design: Patients were randomised to screening by
flexible sigmoidoscopy, faecal blood testing, or both tests. The
flexible sigmoidoscopy examinations were performed by a general
practitioner.
Setting: General practice.
Subjects: 3744 patients aged 50-75 years.
Main outcome measures: Uptake, positive results,
detection of neoplasia, complications, and recall for diagnostic
colonoscopy.
Results: Uptake was significantly higher in the
flexible sigmoidoscopy group (46.6%) than in the faecal blood test
group (31.6%; P<0.001) or than in the group having both tests
(30.1%; P<0.001). Telephone reminders increased uptake of
sigmoidoscopy to 61.8%. In total, 1116 sigmoidoscopy examinations were
performed without major complication. Polyps were found in 19.3% (95%
confidence interval 17.0% to 21.6%) but only 6.8% (5.3% to 8.3%)
had adenomas and 2.4% (1.5% to 3.3%) "high risk" adenomas.
Cancer was detected in four subjects. The faecal blood test yielded
positive results in 0.8% (0.2% to 1.4%) but missed at least one
cancer and 30 cases of adenoma which were found by sigmoidoscopy in the
combined group. Use of histological criteria
shown elsewhere to
correlate with future risk of colorectal cancer
to select
"positive" patients could reduce recall for diagnostic colonoscopy
from about 20% to less than 5%.
Conclusions: Some of the predicted obstacles to
screening with flexible sigmoidoscopy are surmountable. Clear evidence
relating to efficacy will be obtained only from a randomised controlled
trial.
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Key messages
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Introduction |
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Colorectal cancer is the second highest cause of death from cancer in England and Wales.1 Recent evidence suggests that removal of neoplastic lesions at sigmoidoscopy can reduce the incidence of and mortality from distal colorectal cancer.2-6 This has prompted calls for mass screening by flexible sigmoidoscopy. These data, from cohort and case-control studies, however, may be subject to biases, 7 8 giving an overoptimistic impression of efficacy. Given the negative aspects of screening programmes,9 policy makers have an obligation to ensure that the benefits (primarily lives saved) outweigh the costs before programmes are introduced.7 This could be most objectively shown through a randomised controlled trial.7 This feasibility study was conducted to determine key features which could influence the design of such a trial.
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Subjects and methods |
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The study was approved by East Hertfordshire ethics committee.
Study population
The study was conducted in one general practice. The
catchment area had a higher proportion of patients from social classes
I and II (56%) than in England and Wales as a whole (23.3%) and a
lower proportion from ethnic minority groups.10 A list of
practice patients from the family health services authority suggested
that 3933 (29%) of the practice population were in the study age range
(50-75 years). The general practitioner (RA) identified and removed
from the list 189 (4.8%) patients who had died or moved or were
ineligible for the study because of a previous diagnosis of colorectal
neoplasia, investigation of the colon and rectum within the previous 2 years, and physical or mental disease contraindicating screening.
Study design
Households were randomised by using the random number
generator in Minitab and invited, by post, to undergo flexible
sigmoidoscopy, faecal occult blood testing (Haemoccult), or faecal
occult blood testing plus flexible sigmoidoscopy. Reminders were not
routinely sent.
Sample size
It was found that inclusion of all eligible subjects would
give more than 90% power to estimate the true prevalence rate of
adenoma within 2%11 and to detect a 10% difference in
compliance between groups (where one was 50%) at the 5% significance
level.12
Telephone survey of non-responders to flexible sigmoidoscopy
As little was known about reasons for non-uptake of
flexible sigmoidoscopy compared with faecal occult blood
testing,13 a telephone survey of a random sample of 184 non-responders in the flexible sigmoidoscopy group was conducted to
ascertain eligibility and, when appropriate, to make a second offer of
flexible sigmoidoscopy screening.
Flexible sigmoidoscopy
An appointment (date and time), a sachet of laxative
(sodium picosulphate-magnesium citrate (Picolax; Nordic)), and an
explanatory booklet were sent 2 weeks in advance. Appointments could be
changed or cancelled by telephone. Subjects were asked to give written
consent to the examination.
Faecal occult blood test
The 3 day, six sample, diet restricted faecal occult
blood test (Haemoccult, Rohm Pharma) was sent with a prepaid reply
envelope and instruction booklet. The test was developed without
rehydration. Patients were recalled if one or more windows yielded a
positive result.
Faecal occult blood testing and flexible sigmoidoscopy
Subjects were asked to complete the faecal occult
blood test before attending for flexible sigmoidoscopy. The faecal test
was developed blind to the results of the flexible sigmoidoscopy
examination and vice versa. Subjects were recalled for colonoscopy if
either the faecal test yielded positive results or the findings at
flexible sigmoidoscopy fulfilled the criteria described above.
Colonoscopy and histology
Colonoscopy was performed by the general practitioner.
Subjects with adenomas were classified into high and low risk groups on
the basis of lesions found at screening (high risk if at least one
adenoma was
1 cm, villous, or tubulovillous or showed features of
severe dysplasia) on histological examination.5
Analysis
Crude uptake rates were calculated as the number of
responders per group and the number of invited per group.
2 test for contingency tables was used to compare
proportions. All reported P values are two tailed.
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Results |
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Uptake of screening tests
Crude uptake rates are shown in table 1. In the flexible
sigmoidoscopy group the crude uptake rate (46.6%) was significantly
higher than in the faecal occult blood test group (31.6%; P<0.001).
Similarly, it was significantly higher than in the combined test group
whether subjects did both tests (30.1%; P<0.001) or only one of the
two tests (39.5%; P<0.001). Of the subjects in the combined test
group doing only one test, 80% chose flexible sigmoidoscopy (94 v 24). The uptake of flexible sigmoidoscopy in the
combined test group was 37.6%. Although this was significantly lower
than the rate in the flexible sigmoidoscopy only group (46.6%;
P<0.001) it was significantly higher than in the group that underwent
faecal occult blood testing only (31.6%; P<0.01). Conversely, the
crude rate for the faecal test in the combined test group was 32.0%,
which was not significantly different from the comparable rate in the
faecal test group.
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Endoscopic findings at flexible sigmoidoscopy
In total 1116 patients (51% men) underwent flexible
sigmoidoscopy screening without major complication. Polyps were found
in 138 (24.2%) men and 81 (14.9%) women (P<0.001), and two men had
overt malignancy. Three subjects were referred for surgical resection
(a woman with a 3 cm adenoma and two men with cancer). One hundred and
ten subjects with polyps were recommended to return for colonoscopy.
One man refused so his polyps were removed during the screening
examination. A further 90 (41% of those with polyps) subjects with
diminutive rectal polyps had these removed at screening. Seventeen
(7.7%) subjects with diminutive (<5 mm) polyps had no intervention
(two were taking warfarin and one had acute rectal prolapse after the
laxative; contraindications for the others were not elucidated).
Findings at colonoscopy
Altogether 123 subjects (78 men) underwent colonoscopy;
adenomas were removed from 14 at flexible sigmoidoscopy, and 109 were
recalled directly without biopsy at flexible sigmoidoscopy. Eleven
(10% of those who underwent colonoscopy) were found to have adenomas
proximal to the sigmoid colon, 10 of whom had only a single adenoma and
one who had three.
Clinical significance of neoplasias detectable by flexible
sigmoidoscopy
The data on polyps and cancer of the sigmoid colon
and rectum collected at flexible sigmoidoscopy or colonoscopy, or both,
were combined. A diagnosis was assigned according to the most
prognostically significant lesion in the 197 (91%) subjects with
cancer or polyps for whom histological data were available (table 2).
Four subjects had carcinoma (three Dukes' stage A, one Dukes' stage
B) of the sigmoid colon or rectum, and 76 (35% of those with distal
polyps or cancer) had at least one adenoma. Although polyps were
detected in one in five subjects, the prevalence rates of neoplasia
detected at screening were 0.4% for cancer and 6.8% for adenomas. Of
the 76 patients with adenoma, a third were classified as "high
risk" (2.4% (1.5% to 3.3%) of all subjects).
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Comparison of rates of positive diagnosis
In total 854 patients underwent faecal occult blood testing
alone or combined with flexible sigmoidoscopy. Seven (0.8%; 0.2% to
1.4%) had positive results and all underwent colonoscopy. One had a
Dukes' stage C rectal carcinoma, one had a 2 cm adenoma, and a third
had a 2 mm adenoma. A fourth subject had two diminutive adenomas, one
detected at screening and the other at colonoscopy. The three remaining
patients did not have neoplasia.
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Discussion |
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Poor uptake of flexible sigmoidoscopy and the generation of excessive numbers of colonoscopies have been cited as important potential obstacles to mass flexible sigmoidoscopy screening. 14 15 The aim of this study was to evaluate whether these obstacles are surmountable.
The estimated achievable uptake rate of flexible sigmoidoscopy (on the basis of an accurate list of eligible patients and a telephone reminder to non-compliers) of just over 60% compares favourably with the 29% in subjects offered flexible sigmoidoscopy after negative results of the faecal blood screening test in the United Kingdom.16 It is, however, lower than the 81% achieved in a population based Norwegian study in which reminders and press releases were used to boost uptake.17 In an Irish study 68% of volunteers preselected for their eligibility and willingness actually attended for flexible sigmoidoscopy.18
Certain features of the practice (enthusiasm of the primary care team for screening, social class profile of patients) could be expected to encourage higher uptake rates of screening. Both higher and lower uptake rates than those observed in this study would probably be reported, however, if screening were to be offered under different circumstances. It will be important to ascertain how widely rates differ and their most important determinants.
Comments made by subjects in the combined test group revealed possible reasons for the differential uptake rates for the two tests. These included the perceived immediacy of the flexible sigmoidoscopy screening and its results, less distaste for idea of sigmoidoscopy, the additional perceived benefit of consulting the general practitioner while undergoing sigmoidoscopy, and concern that failure to attend for screening might be noted by the doctor. There is support for the latter two factors from other studies of screening. 13 19
Need for colonoscopy
A fundamental prerequisite for the introduction of
screening is that there should be sufficient facilities for diagnosis
and treatment of any lesions detected.20 Colonoscopy
services at present cannot meet diagnostic and follow up needs in many
districts.21
Conclusions
We found that given an accurate list of eligible subjects
and a telephone reminder an uptake rate of over 60% is achievable even
without the use of mass media campaigns. We have also shown that if the
result of flexible sigmoidoscopy screening is defined as "positive"
on the basis of the histological characteristics of polyps removed
during the procedure rather than simply their detection, this will
result in selection of subjects whose current and future risk of large
and villous adenomas or cancer is considerably
increased
5 27-29
and will also reduce the recall rate
for colonoscopy from about 20% to under 5%.
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Acknowledgments |
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We thank the nurses and volunteers at the screening clinic, in particular Sister G Jellis, Mrs K Pearce, Mrs R Ashwell, and Mrs R McMillan; staff of the practice, in particular Mrs S Woods; and staff of the ICRF Colorectal Unit, in particular Mr K Miller and Mrs S Epstein for their assistance with and support for the study and Miss H Crowne for designing the database. We also thank the late Lt Col Sir Martin Gilliat.
Contributors: JECWV had the original idea for the study, formulated the hypothesis, designed the protocol, planned and coordinated the study, and wrote the paper. RA enabled the study to be undertaken in the general practice in which he is a principal; undertook all the flexible sigmoidoscopies and colonoscopies; and contributed from the stage of hypothesis formulation to all aspects of the study design. He contributed suggestions to the paper. SBL provided statistical advice from the stage of formulation of the hypothesis (including initial power calculations) to the study design and performed the randomisation and statistical analyses. She contributed suggestions to the paper. ICT examined all the samples histologically and provided diagnoses; he also contributed suggestions to the paper. JMAN directed the overall programme at the unit on screening for colorectal neoplasia and will act as guarantor. In this study, he provided guidance and support throughout, particularly in the development of the original idea, hypothesis formulation, protocol design, and writing of the paper.
Funding: Smith-Kline-Beecham donated the flexible sigmoidoscopes.
Conflict of interest: None.
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References |
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45 years [abstract].
Gut 198;28:10. (Accepted 16 December 1997)
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