Higher Adenoma Detection Rates at Screening Associated With Lower Long-Term Colorectal Cancer Incidence and Mortality

Abstract

Background & aims: Detection and removal of adenomas reduces colorectal cancer (CRC) risk. The impact of adenoma detection rates (ADRs) on long-term CRC incidence and mortality is unknown. We investigated this using data from the UK Flexible Sigmoidoscopy Screening Trial.

Methods: Of 167,882 UK Flexible Sigmoidoscopy Screening Trial participants, 40,085 were in the intervention arm and underwent flexible sigmoidoscopy screening at 13 trial centers. The median follow-up time was 17 years. At each center, 1 endoscopist performed most flexible sigmoidoscopies. Multivariable logistic regression was used to classify centers into high-, intermediate-, and low-detector groups based on their main endoscopist's ADR. We calculated the incidence and mortality of distal and all-site CRC, and estimated hazard ratios (HRs) with 95% CIs using Cox regression.

Results: Five, 4, and 4 centers, respectively, were classified into the high-detector, intermediate-detector, and low-detector groups. The average ADRs in each respective group were 15%, 12%, and 9%. Distal CRC incidence and mortality were reduced among those screened compared with controls in all groups, and effects of screening varied significantly by detector ranking, with larger reductions in incidence and mortality seen in the high-detector group (incidence: HR, 0.34; 95% CI, 0.27-0.42; mortality: HR, 0.22, 95% CI, 0.13-0.37) than in the low-detector group (incidence: HR, 0.55; 95% CI, 0.44-0.68; mortality: HR, 0.54; 95% CI, 0.34-0.86). Similar results were observed for all-site CRC, with larger effects seen in the high-detector (incidence: HR, 0.58; 95% CI, 0.50-0.67; mortality: HR, 0.52; 95% CI, 0.39-0.69) than in the low-detector group (incidence: HR, 0.72; 95% CI, 0.61-0.85; mortality: HR, 0.68; 95% CI, 0.51-0.92), although the heterogeneity was not statistically significant.

Conclusions: Higher ADRs at screening provide greater long-term protection against CRC incidence and mortality. Isrctn.org, number: ISRCTN28352761.

Keywords: Adenoma Detection Rate; Colorectal Cancer; Flexible Sigmoidoscopy; Screening.

Figure 1

Hazard ratios for distal colorectal cancer incidence and mortality by detector ranking. Rates are per 100,000 person-years. (A and C) Hazard ratios are for the invited to screening vs control arm; (B and D) hazard ratios are for the screened vs control arm. P values from χ² test for heterogeneity of effect by detector ranking. ∗Adjusted for noncompliance.

Figure 2

Hazard ratios for all-site colorectal cancer incidence and mortality by detector ranking. Rates are per 100,000 person-years. (A and C) Hazard ratios are for the invited to screening vs control arm; (B and D) hazard ratios are for the screened vs control arm. P values from χ² test for heterogeneity of effect by detector ranking. ∗Adjusted for noncompliance.

Figure 3

Average rate ratios for distal colorectal cancer incidence and mortality by detector ranking. Plotted points and 95% CIs are for the 3-year rolling average rate ratios. The average annual rate ratios over years 6 to 10 and years 11 to 16 are detailed. (A and C) Rate ratios for the invited to screening vs control arm; (B and D) rate ratios for the screened vs control arm. (D) The rate ratio is not presented for the final time point owing to few events in the high-detector group. ∗Adjusted for noncompliance.

Figure 4

Number needed to screen to prevent 1 colorectal cancer (A) diagnosis or (B) death over 17 years by detector ranking.

Supplementary Figure 1

Trial profile flow diagram. ∗A total of 16,014 individuals were not required because the attendance of 40,000 participants at screening for which the trial was funded had been reached. †In total, 12 participants were lost to follow-up because they could not be traced through national data sources; 6 from the control arm and 6 from the intervention arm, of whom 2 had undergone screening. CRC, colorectal cancer.

Supplementary Figure 2

Cumulative colorectal cancer incidence and mortality by detector-ranking group. Kaplan–Meier estimates of cumulative colorectal cancer incidence and mortality by time from randomization and detector-ranking group. (A, C, E, and G) Intention-to-treat analyses, (B, D, F, and H) per-protocol analyses.

Supplementary Figure 3

Hazard ratios for distal colorectal cancer incidence and mortality by detector-ranking group and age group in intention-to-treat analyses. Rates are per 100,000 person-years. Hazard ratios are for the invited to screening vs control arm in intention-to-treat analyses (A and B) among participants aged 55-59 years, (C and D) among participants aged 60-64 years.

Supplementary Figure 4

Hazard ratios for distal colorectal cancer incidence and mortality by detector-ranking group and sex in intention-to-treat analyses. Rates are per 100,000 person-years. Hazard ratios are for the invited to screening vs control arm in intention-to-treat analyses (A and B) among men, (C and D) among women.