Jocelyn Chamberlain

Randomised controlled trial of faecal-occult-blood screening for colorectal cancer

BACKGROUND There is growing evidence that faecal-occult-blood (FOB) screening may reduce colorectal cancer (CRC) mortality, but this reduction in CRC mortality has not been shown in an unselected population-based randomised controlled trial. The aim of this study was to assess the effect of FOB screening on CRC mortality in such a setting. METHODS Between February, 1981, and January, 1991, 152,850 people aged 45-74 years who lived in the Nottingham area of the UK were recruited to our study. Participants were randomly allocated FOB screening (76,466) or no screening (controls; 76,384). Controls were not told about the study and received no intervention. Screening-group participants were sent a Haemoccult FOB test kit with instructions from their family doctor. FOB tests were not rehydrated and dietary restrictions were imposed only for retesting borderline results. Individuals with negative FOB tests at the first screening, together with those who tested positive but in whom no neoplasia was found on colonoscopy, were invited to take part in further screening every 2 years. Screening was stopped in February, 1995, by which time screening-group participants had been offered FOB tests between three and six times. Screening-group participants who had a positive test were offered full colonoscopy. All participants were followed up until June, 1995. The primary outcome measure was CRC mortality. FINDINGS Of the 152,850 individuals recruited to the study, 2599 could not be traced or had emigrated and were excluded from the analysis. Thus, there were 75,253 participants in the screening group and 74,998 controls. 44,838 (59.6%) screening-group participants completed at least one screening. 28,720 (38.2%) of these individuals completed all the FOB tests they were offered and 16,118 (21.4%) completed at least one screening but not all the tests they were offered. 30,415 (40.4%) did not complete any test. Of 893 cancers (20% stage A) diagnosed in screening-group participants (CRC incidence of 1.49 per 1000 person-years), 236 (26.4%) were detected by FOB screening, 249 (27.9%) presented after a negative FOB test or investigation, and 400 (44.8%) presented in non-responders. The incidence of cancer in the control group (856 cases, 11% stage A) was 1.44 per 1000 person-years. Median follow-up was 7.8 years (range 4.5-14.5). 360 people died from CRC in the screening group compared with 420 in the control group-a 15% reduction in cumulative CRC mortality in the screening group (odds ratio=0.85 [95%; CI 0.74-0.98], p = 0.026). INTERPRETATION Our findings together with evidence from other trials suggest that consideration should be given to a national programme of FOB screening to reduce CRC mortality in the general population.

RANDOMISED, CONTROLLED TRIAL OF FAECAL OCCULT BLOOD SCREENING FOR COLORECTAL CANCER: Results for First 107 349 Subjects

To assess the effectiveness of screening by faecal occult blood tests, 107,349 people without symptoms of colorectal disease identified from general practitioner records have been randomly allocated to test and control groups. 53,464 test subjects were invited to carry out the screening test; 27,651 (53%) of the 52,258 who received the tests did so. Further investigation of the 618 (2.3%) with positive tests showed 63 cancers (52% stage A) and 367 adenomas (266 subjects). Rescreening of subjects with negative results every 2 years (9510 first rescreen, 3639 second) has shown a significant fall in the rate of positive results (1.7% of 7344; 0.3% of 2906). Cancers have also been diagnosed in 20 subjects presenting in the interval between a negative test and rescreening, and in 83 non-responders. The incidence of cancer in the control group (123 subjects; 10.6% stage A) was 0.72 per 1000 person-years. Cancers detected by screening were at a less advanced pathological stage, but it is too early to show any effect of screening on mortality from colorectal cancer.

Cancer Screening in the European Union

(1) Article 152 of the Treaty provides that Community action is to complement national policies and be directed towards improving public health, preventing human illness and diseases, and obviating sources of danger to human health. Such action shall cover the fight against the major health scourges, by promoting L 327/34 Official Journal of the European Union 16.12.2003 Population-based, Nationwide Rollout complete

VALIDITY OF CLINICAL EXAMINATION AND MAMMOGRAPHY AS SCREENING TESTS FOR BREAST CANCER

This study is aiming to determine the validity and observer variability of clinical examination and mammography as screening tests for breast cancer. Women over the age of forty are given two independent clinical examinations of the breasts, and mammograms are taken and read independently by two radiologists. This paper presents the results of screening the first 1215 women to be enrolled in the study. At their first screening attendance, 231 women (19%) were referred for surgical opinion, 119 (9-8%) underwent biopsy, and cancer was diagnosed in 17 (1-4%). 2 further cancers were diagnosed in the ensuing six months among women who had been negative on initial screening, representing a false-negative rate of 2 out of 19 (11%). Clinical examination resulted in 189 referrals (15-6%), 90 biopsies (7-4%), and detected 11 cancers; corresponding figures for mammography were 76 referrals (6-3%), 55 biopsies ((4-5%), and 14 cancers. Observer variability was greater for clinical examination than for mammography. These early results suggest that as a screening test mammography compares favourably with clinical examination, but both tests are necessary if many false negatives are to be avoided.

Screening for breast cancer

The hypothesis underlying the screening of well women for breast cancer is that detection and treatment of cancers at an asymptomatic stage enables cure of lesions which would already be incurable if left until the women presented with symptoms. Whether or not this can be achieved depends not only on the ability of a screening test to detect asymptomatic disease, but also on biological factors affecting the rate of growth and spread of the cancer. The natural history of breast cancer is renowned for its variability in growth rates, some lesions progressing very slowly over several decades while others may progress to incurability within days. The former group would probably be curable anyway, even if left until symptomatic presentation, while the latter group might well be incurable even before they became detectable by screening. It is for the group of breast cancers between these two extremes that screening programmes have potential.

Screening for Cancer of the Breast

Breast cancer is the most common cancer among women, with an estimated 308 100 cancers worldwide in 1985, accounting for 19.1% of all cancers [62]. It is the most common cancer in women in all developed countries, apart from Japan. The highest recorded incidence rates are in North America, with an age-standardised rate in 1985 of 84.8 per 100 000. The lowest reported rates are 11.1 per 100 000 in Western Africa and 14.6 per 100 000 in China. In England and Wales, the age-standardised incidence rate in 1987 was 58.0 per 100 000, representing 23 740 new cases [59]. Breast cancer in males is rare, and will not be considered further in this chapter.