Effect of flexible sigmoidoscopy screening on colorectal cancer incidence and mortality: a randomized clinical trial

Abstract

Importance: Colorectal cancer is a major health burden. Screening is recommended in many countries.

Objective: To estimate the effectiveness of flexible sigmoidoscopy screening on colorectal cancer incidence and mortality in a population-based trial.

Design, setting, and participants: Randomized clinical trial of 100,210 individuals aged 50 to 64 years, identified from the population of Oslo city and Telemark County, Norway. Screening was performed in 1999-2000 (55-64-year age group) and in 2001 (50-54-year age group), with follow-up ending December 31, 2011. Of those selected, 1415 were excluded due to prior colorectal cancer, emigration, or death, and 3 could not be traced in the population registry.

Interventions: Participants randomized to the screening group were invited to undergo screening. Within the screening group, participants were randomized 1:1 to receive once-only flexible sigmoidoscopy or combination of once-only flexible sigmoidoscopy and fecal occult blood testing (FOBT). Participants with positive screening test results (cancer, adenoma, polyp ≥10 mm, or positive FOBT) were offered colonoscopy. The control group received no intervention.

Main outcomes and measures: Colorectal cancer incidence and mortality.

Results: A total of 98,792 participants were included in the intention-to-screen analyses, of whom 78,220 comprised the control group and 20,572 comprised the screening group (10,283 randomized to receive a flexible sigmoidoscopy and 10,289 to receive flexible sigmoidoscopy and FOBT). Adherence with screening was 63%. After a median of 10.9 years, 71 participants died of colorectal cancer in the screening group vs 330 in the control group (31.4 vs 43.1 deaths per 100,000 person-years; absolute rate difference, 11.7 [95% CI, 3.0-20.4]; hazard ratio [HR], 0.73 [95% CI, 0.56-0.94]). Colorectal cancer was diagnosed in 253 participants in the screening group vs 1086 in the control group (112.6 vs 141.0 cases per 100,000 person-years; absolute rate difference, 28.4 [95% CI, 12.1-44.7]; HR, 0.80 [95% CI, 0.70-0.92]). Colorectal cancer incidence was reduced in both the 50- to 54-year age group (HR, 0.68; 95% CI, 0.49-0.94) and the 55- to 64-year age group (HR, 0.83; 95% CI, 0.71-0.96). There was no difference between the flexible sigmoidoscopy only vs the flexible sigmoidoscopy and FOBT screening groups.

Conclusions and relevance: In Norway, once-only flexible sigmoidoscopy screening or flexible sigmoidoscopy and FOBT reduced colorectal cancer incidence and mortality on a population level compared with no screening. Screening was effective both in the 50- to 54-year and the 55- to 64-year age groups.

Trial registration: clinicaltrials.gov Identifier: NCT00119912.

Conflict of interest statement

Conflict of interest disclosure: Michael Bretthauer is member of the European scientific advisory board of Exact Sciences and has received equipment for testing in scientific studies from Olympus, Fujinon, Falk Phgroup and CCS Healthcare. Holme, Løberg, Skovlund, Schneede, Aas, Hoff, Eide, Tveit, Kalager, Hernán report no conflicts of interest.

Figures

Figure 1. Flowchart. Norwegian Colorectal Cancer Prevention trial (NORCCAP)

Individuals aged 55–64 and 50–54 years were invited to screening in 1999–2000 and in 2001, respectively. The screening examination date originally proposed in the invitation letter was considered the date of study entry for the screening group. A randomly allocated date (Jan 1st 1999 – Dec 31st 2000 for the 55–64 year age-group and Jan 1st – Dec 31st 2001 for the 50–54 year age-group) was considered the date of study entry for the control group.

Figure 2. Cumulative probability of colorectal cancer incidence and mortality

The panels show cumulative probability for colorectal cancer incidence (panels A and C) and mortality (panels B and D), for the colorectum overall and for the distal colon. HR: Hazard ratio. CI: Confidence interval. At-risk table, panel A and C [Table: see text] At-risk table, panel B and D [Table: see text]

Figure 2. Cumulative probability of colorectal cancer incidence and mortality

The panels show cumulative probability for colorectal cancer incidence (panels A and C) and mortality (panels B and D), for the colorectum overall and for the distal colon. HR: Hazard ratio. CI: Confidence interval. At-risk table, panel A and C [Table: see text] At-risk table, panel B and D [Table: see text]

Figure 2. Cumulative probability of colorectal cancer incidence and mortality

The panels show cumulative probability for colorectal cancer incidence (panels A and C) and mortality (panels B and D), for the colorectum overall and for the distal colon. HR: Hazard ratio. CI: Confidence interval. At-risk table, panel A and C [Table: see text] At-risk table, panel B and D [Table: see text]

Figure 2. Cumulative probability of colorectal cancer incidence and mortality

The panels show cumulative probability for colorectal cancer incidence (panels A and C) and mortality (panels B and D), for the colorectum overall and for the distal colon. HR: Hazard ratio. CI: Confidence interval. At-risk table, panel A and C [Table: see text] At-risk table, panel B and D [Table: see text]

Figure 3

Figure 3A: Yearly risk ratio (with error bars) of CRC incidence for the screening group relative to the control group. Figure 3B: Yearly risk ratio (with error bars) of CRC mortality for the screening group relative to the control group.

Figure 3

Figure 3A: Yearly risk ratio (with error bars) of CRC incidence for the screening group relative to the control group. Figure 3B: Yearly risk ratio (with error bars) of CRC mortality for the screening group relative to the control group.

Figure 4

Figure 4A: Yearly risk ratio (with error bars) for overall colorectal cancer incidence in screening compliers (n=12,955) and the screening group (compliers and noncompliers, n=20,572) relative to the control group (n=78,220). Figure 4B: Yearly risk ratio (with error bars) for distal colorectal cancer incidence in screening compliers (n=12,955) and for overall colorectal cancer incidence in the screening group (compliers and noncompliers, n=20,572) relative to the control group (n=78,220).

Figure 4

Figure 4A: Yearly risk ratio (with error bars) for overall colorectal cancer incidence in screening compliers (n=12,955) and the screening group (compliers and noncompliers, n=20,572) relative to the control group (n=78,220). Figure 4B: Yearly risk ratio (with error bars) for distal colorectal cancer incidence in screening compliers (n=12,955) and for overall colorectal cancer incidence in the screening group (compliers and noncompliers, n=20,572) relative to the control group (n=78,220).