Risk-stratified screening and colorectal cancer incidence and mortality: A retrospective study from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial.

Objective: To determine whether risk stratification can optimize the benefits of flexible sigmoidoscopy (FSG) screening.

Methods: The Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial was conducted from 1993 to 2001 in the United States. A colorectal cancer (CRC) risk stratification tool was developed in the control arm (n = 64,207) from the PLCO cohort and validated in the UK Biobank (n = 270,726). PLCO participants (n = 130,021) were classified into low-, medium-, and high-risk groups. Cumulative incidence and mortality were estimated using the Kaplan-Meier method. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the associations between screening and CRC incidence and mortality.

Results: The CRC risk stratification tool was based on age, gender, body mass index, smoking status, family history of CRC, diabetes, regular use of aspirin, and CRC screening history. Compared with the control arm, FSG screening was significantly associated with a reduction in mortality in both the medium-risk (HR = 0.76, 95% CI = 0.63-0.92) and high-risk groups (0.58, 0.46-0.73), but not in the low-risk group (0.85, 0.61-1.19). FSG screening also reduced distal CRC incidence and mortality in the medium-risk and high-risk groups. Furthermore, it was associated with a reduction in incidence (0.74, 0.59-0.92) and mortality (0.59, 0.40-0.87) of proximal colon cancer in the high-risk group.

Conclusions: FSG screening yielded more benefits for the high-risk group than for the low-risk and medium-risk groups, supporting the development of a risk-stratified CRC screening strategy.