Figure 1 shows the flow chart for the 55
736 people who were randomised. Altogether, 753 cases of colorectal cancer or death occurred before the study entry date, including four people with previous colorectal cancer who were erroneously screened. This left 13
653 people in the screening group and 41
092 in the control group eligible for analyses (fig 1). Censoring owing to emigration occurred for 1196 people, and 21 people were censored as a result of colorectal malignancy other than colorectal carcinoma (13 neuroendocrine (carcinoid) tumours and eight squamous cell carcinomas). In the screening group, 459 people were excluded from examination, according to the described exclusion criteria, but included in the intention to screen analyses.
Fig 1Flow chart for Norwegian Colorectal Cancer Prevention trial 1 cohort screened January 1999 to December 2001
The two groups were similar in the distribution of age (mean 59 years) and sex (50% female in both groups). Of the 13
653 people eligible, 8846 had a screening examination, giving an attendance rate of 64.8% (67% with exclusion of those not examined owing to exclusion criteria). Compliance was slightly higher in women than in men (65.9% (4554/6907) v
62.1% (4292/6916)). The attending and non-attending groups had similar age distribution (mean 58.4 and 58.5 years, with a range of 55-64 for both groups). Mean insertion of the endoscope was 48.9 (SD=15.7) cm for men and 44.0 (14.2) cm for women, as measured with a straightened endoscope. No severe complications occurred during flexible sigmoidoscopy. At screening, a neoplastic lesion was found in 19% (1685/8846) of people screened, and 5.0% (440/8846) of attenders had high risk adenoma (≥10 mm in diameter, high grade dysplasia or villous components) or invasive cancer.13
Out of 33 prevalent colorectal cancers detected by screening, 17 were in the 6915 people invited for flexible sigmoidoscopy only (2.5 per 1000 invited) and 16 in the 6908 people invited for combined flexible sigmoidoscopy and faecal occult blood testing (2.3 per 1000 invited).
The compliance for colonoscopy work-up was 97% (1812/1872). Ninety per cent (1617/1812) of colonoscopies took place without sedation or analgesia. The rate of caecal intubation at first attempt was 89% (1623/1812). In the 189 patients in whom baseline colonoscopy work-up was initially incomplete, the caecum was reached in 12 on a second attempt, double contrast barium enema was done in 52, and six were referred directly to surgery owing to distal tumour. Thus, 70 patients had their entire colon visualised during work-up or post-surgical surveillance. In the remaining 119 people with incomplete visualisation of the caecum, none had incident colorectal cancer at six to eight year follow-up. In addition to people with neoplasia at flexible sigmoidoscopy, colonoscopy work-up was done in 349 patients because of a positive faecal occult blood test (n=150), symptoms (n=65, including one case of colorectal carcinoma), hyperplastic polyp >10 mm (n=28), poor bowel cleansing at flexible sigmoidoscopy (n=24), tissue sample lost at screening (n=22), and other reasons (n=60).
Median follow-up after inclusion in the trial was seven (range six to eight) years for incident colorectal cancer and six (range five to seven) years for mortality from colorectal cancer. The cumulative hazard rate starts at a high level in the screening group owing to detection of prevalent colorectal cancer cases at screening (fig 2). We found no difference in the cumulative hazard of colorectal cancer between the screening group and the control group (intention to screen analysis; 134.5 v
131.9 cases per 100
000 person years). The accumulated number of colorectal cancers after six to eight years of follow-up was 123 in the screening group, including 33 screen detected tumours, and 362 in the control group (table). In the two screening groups, 54 accumulated colorectal cancers occurred in the flexible sigmoidoscopy group (7.9 per 1000) and 69 (10.1 per 1000) in the group invited to combined flexible sigmoidoscopy and faecal occult blood testing. When we restricted the cumulative hazard plot to attenders and rectosigmoidal cancers only, the line crosses that of the control group, suggesting an effect of polypectomy for left sided colorectal cancer in those attending for screening (fig 3). The cumulative incidence of rectosigmoidal cancer was 35 cases in 8846 attenders (58 per 100
000 person years) and 217 in 41
092 controls (79 per 100
000 person years) (P=0.103). Of 90 post-screen incident colorectal cancers in the screening group, 37 appeared among 6915 people invited for flexible sigmoidoscopy only (5.4 per 1000) compared with 53 in 6908 people invited for combined flexible sigmoidoscopy and faecal occult blood testing (7.7 per 1000).
Fig 2Cumulative hazard for colorectal cancer in screening and control groups
Accumulated cases (accumulated No/1000 people) of colorectal cancer in subsets of screening group and control group after six to eight years’ follow-up
Fig 3Cumulative hazard for rectosigmoidal cancer among attenders compared with control group
A total of 24 of 13
653 people in the screening group and 99 of 41
092 in the control group died from colorectal cancer during follow-up. In the screening group as a whole (intention to screen), total mortality was reduced by 27% (hazard ratio 0.73, 95% confidence interval 0.47 to 1.13, P=0.16) for colorectal cancer and by 37% (0.63, 0.34 to 1.18, P=0.15) for rectosigmoidal cancer compared with the control group. For those actually screened, total mortality was reduced by 59% (hazard ratio 0.41, 0.21 to 0.82, P=0.011) for colorectal cancer and by 76% (0.24, 0.08 to 0.76, P=0.016) for rectosigmoidal cancer; this corresponded to three and 57 deaths from rectosigmoidal cancer. All cause mortality was similar in the screening group and the control group (hazard ratio 1.02, 0.98 to 1.07, P=0.28).
We found a more favourable stage distribution for patients with screen detected colorectal cancer compared with those in the control group and the non-attending group (table). Almost half of the total number of colorectal cancers among attenders (33/71) were screen detected tumours, and 27 of the 38 post-screen colorectal cancers were localised proximal to the rectum and sigmoid colon. In attenders, 36 of 71 colorectal cancers were localised proximal to the rectosigmoid colon (4.07/1000 attenders) compared with 145 of 362 in the control group (3.53/1000 people, 3.74/1000 if nine tumours with undefined localisation were to be classified as proximal). Case fatalities from colorectal cancer diagnosed within the update period of cause of death registrations (that is, including 2005) were 9/66 (14%) in the group of attenders (2/33 (6%) screen detected) compared with 15/38 (39%) among non-attenders and 99/308 (32%) in the control group. Excluding screen detected colorectal cancers, deaths from post-screen detected colorectal cancer among attenders (“interval cancers”) were 7/33 (21%).