Long-term Risk of Colorectal Cancer and Related Deaths After a Colonoscopy With Normal Findings

Abstract

Importance: Guidelines recommend a 10-year rescreening interval after a colonoscopy with normal findings (negative colonoscopy results), but evidence supporting this recommendation is limited.

Objective: To examine the long-term risks of colorectal cancer and colorectal cancer deaths after a negative colonoscopy result, in comparison with individuals unscreened, in a large, community-based setting.

Design, setting, and participants: A retrospective cohort study was conducted in an integrated health care delivery organization serving more than 4 million members across Northern California. A total of 1 251 318 average-risk screening-eligible patients (age 50-75 years) between January 1, 1998, and December 31, 2015, were included. The study was concluded on December 31, 2016.

Exposures: Screening was examined as a time-varying exposure; all participants contributed person-time unscreened until they were either screened or censored. If the screening received was a negative colonoscopy result, the participants contributed person-time in the negative colonoscopy results group until they were censored.

Main outcomes and measures: Using Cox proportional hazards regression models, the hazard ratios (HRs) for colorectal cancer and related deaths were calculated according to time since negative colonoscopy result (or since cohort entry for those unscreened). Hazard ratios were adjusted for age, sex, race/ethnicity, Charlson comorbidity score, and body mass index.

Results: Of the 1 251 318 patients, 613 692 were men (49.0%); mean age was 55.6 (7.0) years. Compared with the unscreened participants, those with a negative colonoscopy result had a reduced risk of colorectal cancer and related deaths throughout the more than 12-year follow-up period, and although reductions in risk were attenuated with increasing years of follow-up, there was a 46% lower risk of colorectal cancer (hazard ratio, 0.54; 95% CI, 0.31-0.94) and 88% lower risk of related deaths (hazard ratio, 0.12; 95% CI, 0.02-0.82) at the current guideline-recommended 10-year rescreening interval.

Conclusions and relevance: A negative colonoscopy result in average-risk patients was associated with a lower risk of colorectal cancer and related deaths for more than 12 years after examination, compared with unscreened patients. Our study findings may be able to inform guidelines for rescreening after a negative colonoscopy result and future studies to evaluate the costs and benefits of earlier vs later rescreening intervals.

Figure 1.. Flow Diagram for Selection of Screening-Eligible Cohort

FIT, fecal immunochemical testing; FOBT, fecal occult blood testing; and KPNC, Kaiser Permanente Northern California.

Figure 2.. Adjusted Risk of Colorectal Cancer Incidence by Time Interval After a Negative Colonoscopy Result

Hazard ratios were obtained by time-varying multivariable Cox proportional hazards models and adjusted for age, sex, race/ethnicity, Charlson comorbidity index score, body mass index, and screening level exposure status prior to negative colonoscopy result (defined as an examination with normal findings). Error bars indicate 95% CIs.

Figure 3.. Adjusted Risk of Colorectal Cancer Mortality by Time Interval After a Negative Colonoscopy Result

Hazard ratios were obtained by time-varying multivariable Cox proportional hazards models and adjusted for age, sex, race/ethnicity, Charlson comorbidity index score, body mass index, and screening level exposure status prior to negative colonoscopy result (defined as an examination with normal findings). Error bars indicate 95% CIs.

Figure 4.. Adjusted Risks of Colorectal Cancer by Time Interval After a Negative Colonoscopy Result: Site- and Stage-Specific Analyses

Adjusted risks for proximal (A), distal (B), early-stage (C), and advanced-stage (D) colorectal cancer. Hazard ratios were obtained by time-varying multivariable Cox proportional hazards models and adjusted for age, sex, race/ethnicity, Charlson comorbidity index score, body mass index, and screening level exposure status prior to negative colonoscopy result (defined as an examination with normal findings). Error bars indicate 95% CIs.