Comparing CT colonography and flexible sigmoidoscopy: a randomised trial within a population-based screening programme.

IMPORTANCE AND AIMS: The role of CT colonography (CTC) as a colorectal cancer (CRC) screening test is uncertain. The aim of our trial was to compare participation and detection rate (DR) with sigmoidoscopy (flexible sigmoidoscopy (FS)) and CTC in a screening setting. DESIGN SETTING AND PARTICIPANTS: We conducted two randomised clinical trials (RCTs). (1) Participation RCT: individuals, aged 58 years, living in Turin (Italy), were randomly assigned to be invited to FS or CTC screening; (2) detection RCT: residents in northern Italy, aged 58-60, giving their consent to recruitment, were randomly allocated to CTC or FS. Polyps ≥6 mm at CTC, or 'high-risk' distal lesions at FS, were referred for colonoscopy (TC). MAIN OUTCOME MEASURES: Participation rate (proportion of invitees examined); DR of advanced adenomas or CRC (advanced neoplasia (AN)). RESULTS: Participation was 30.4% (298/980) for CTC and 27.4% (267/976) for FS (relative risk (RR) 1.1; 95% CI 0.98 to 1.29). Among men, participation was higher with CTC than with FS (34.1% vs 26.5%, p=0.011). In the detection RCT, 2673 subjects had FS and 2595 had CTC: the AN DR was 4.8% (127/2673, including 9 CRCs) with FS and 5.1% (133/2595, including 10 CRCs) with CTC (RR 1.08; 95% CI 0.85 to 1.37). Distal AN DR was 3.9% (109/2673) with FS and 2.9% (76/2595) with CTC (RR 0.72; 95% CI 0.54 to 0.96); proximal AN DR was 1.2% (34/2595) for FS vs 2.7% (69/2595) for CTC (RR 2.06; 95% CI 1.37 to 3.10). CONCLUSIONS AND RELEVANCE: Participation and DR for FS and CTC were comparable. AN DR was twice as high in the proximal colon and lower in the distal colon with CTC than with FS. Men were more likely to participate in CTC screening. TRIAL REGISTRATION NUMBER: NCT01739608; Pre-results.

Invitation strategies for colorectal cancer screening programmes: The impact of an advance notification letter.

AIM: To estimate the impact of an advance notification letter on participation in sigmoidoscopy (FS) and fecal immunochemical test (FIT) screening. METHODS: Eligible subjects, invited in 3 Italian population based programmes using FS and in 5 using FIT, were randomised (1:1:1), within GP, to: A) standard invitation letter; B) advance notification followed after 1month by the standard invitation; and C) B+indication to contact the general practitioner (GP) to get advice about the decision to be screened. We calculated the 9-month attendance and the incremental cost of each strategy. We conducted a phone survey to assess GP's utilization and predictors of participation. RESULTS: The advance notification was associated with a 20% increase in the attendance among 15,655 people invited for FS (B vs A - RR: 1.17, 95% CI: 1.10-1.25; C vs A - RR: 1.19, 95% CI: 1.12-1.27); the incremental cost ranged between 10 and 9 Euros. Participation in FIT screening (N=23,543) was increased only with simple pre-notification (B vs A - RR: 1.06, 95% CI: 1.02-1.10); the incremental cost was 22.5 Euros. GP consultation rate was not increased in group C. CONCLUSIONS: An advance notification represents a cost-effective strategy to increase participation in FS screening; its impact on the response to FIT screening was limited.

Offering people a choice for colorectal cancer screening.

OBJECTIVES: To assess the population coverage and diagnostic yield of offering an immunochemical faecal occult blood test (FIT) to non-responders to a flexible sigmoidoscopy (FS) invitation. DESIGN: A cohort study conducted in a population-based colorectal cancer (CRC) screening programme. In this programme, eligible men and women aged 58 (Turin; 43,748 subjects) or 60 (Verona; 19,970 subjects) are invited, with a personal letter signed by their general practitioner, to undergo an FS. Bowel preparation is limited to a single enema self-administered at home. Subjects in whom one distal polyp >5 mm (≥ 10 mm in Turin) or at least one adenoma (one advanced adenoma or more than two adenomas in Turin) is detected at FS are referred for colonoscopy. People who do not respond to the invitation to undergo an FS are invited to have an FIT (OC-Sensor; Eiken, Tokyo, Japan; single sample, cut-off 100 ng/ml). Attendance rate and neoplasia yield were analysed in four consecutive birth cohorts. RESULTS: Overall participation rate for the FS invitation was 39.3% in Verona and 29.9% in Turin. Of the eligible non-responders to the FS invitation, 19.3% (95% CI 18.9% to 19.7%) underwent an FIT. As a result, the proportion of people undergoing screening by FS or FIT was 55.2% in Verona and 39.3% in Turin, with no gender differences in either centre. FIT detected 8.3% of all advanced adenomas and 20.4% of all CRCs diagnosed at screening. CONCLUSIONS: A strategy involving the sequential offer of FS and FIT is a feasible and efficient approach. FIT in people not attending for FS increases screening uptake and detection of advanced adenomas and CRCs.

Acceptability and side-effects of colonoscopy and sigmoidoscopy in a screening setting.

OBJECTIVE: Quantitative information on adverse reactions associated with colorectal cancer (CRC) screening tests is useful to estimate the balance between benefit and risk in different strategies. SETTING: Six Italian screening centres. METHODS: Thirty-day active follow-up (interview about side-effects and acceptability of the screening procedure and review of hospital admissions) among average-risk people undergoing flexible sigmoidoscopy (FS), total colonoscopy (TC), fecal immunochemical test (FIT) in a multicentre randomized trial of CRC screening. Multivariable logistic models were used to assess determinants of completion rate and self-reported pain. RESULTS: The attendance rate following the first invitation and mail reminder was 28.2% (1696/6018) in the FS and 23.0% (1382/6021) in the TC arm. Response rate to the 30-day follow-up questionnaire was 88.6% (1502/1696) among people undergoing FS, and 86.7% (1198/1382) among those undergoing TC. The proportion of people complaining of serious reactions following bowel preparation (odds ratio [OR], 5.17; 95% confidence interval [CI] 3.70-7.24) or reporting severe pain immediately after the exam (OR, 1.86; 95% CI 1.47-2.34) was higher for TC than for FS. The most common post-procedural complaints were abdominal distension and pain. People mentioning pain or bowel distension following preparation were more likely to report severe pain both after FS (OR, 2.13; 95% CI 1.52-2.97) and TC (OR: 2.03; 95% CI 1.41-2.90). The 30-day hospitalization rate was similar after FS, TC and FIT. CONCLUSIONS: Screenees reported higher pain levels after TC than FS. The proportion of people complaining of severe side effects after discharge was similar. Bowel preparation was poorly tolerated by people undergoing TC. Subjects' reactions to the bowel preparation was predictive of post-procedural discomfort. A commitment of at least 48 hours was required of people undergoing TC, compared with 3-4 for FS.

Comparing attendance and detection rate of colonoscopy with sigmoidoscopy and FIT for colorectal cancer screening.

BACKGROUND & AIMS: We conducted a study to estimate population coverage and detection rate (DR) achievable through different strategies of colorectal cancer (CRC) screening. METHODS: A population-based multicenter randomized trial comparing 3 strategies was used: (1) biennial immunologic fecal occult blood test (FIT), (2) "once only" sigmoidoscopy (FS), and (3) "once only" colonoscopy (TC). A random sample of men and women, aged 55 to 64 years, was drawn from general practitioners' (GP) rosters. Eligible subjects, randomized within GP, were mailed a personal invitation. Nonresponders in groups 2 and 3 were invited again at 12 and 24 months. Screenees with "high-risk" distal polyps (villous component >20%, high-grade dysplasia, CRC, size >or=10 mm, >2 adenomas) at FS, or with positive FIT, were referred for TC. RESULTS: The attendance rate was 32.3% (1965/6075) for FIT, 32.3% (1944/6018) for FS, 26.5% (1597/6021) for TC. FIT detected 2 patients with CRC (0.1%) and 21 with an advanced adenoma (1.1%). The corresponding figures were as follows: 12 (0.6%) and 86 (4.5%) patients, respectively, for FS; 13 (0.8%) and 100 (6.3%) patients, respectively, for TC. To detect 1 advanced neoplasm, it would be necessary to invite 264 people with FIT, 60 with FS, 53 with TC. FS would have detected 27.3% of the proximal advanced neoplasms detected at TC. Assuming the same participation rate at TC as at FS, 48 TCs would be necessary to detect 1 additional advanced neoplasm missed by FS. CONCLUSIONS: When participants are offered 1 screening test, participation is lower in a TC than in an FS program. However, DR of advanced neoplasia is higher with TC.