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Screening with flexible sigmoidoscopy reduces mortality risk

Contrary to current guidelines, new research published in Annals of Internal Medicine suggests that colorectal cancer screening with flexible sigmoidoscopy reduces risk for death, indicating that existing recommendations need to be reassessed.

“The 2016 U.S. Preventive Services Task Force (USPSTF) evidence report on colorectal cancer screening concluded that no colorectal cancer screening methods reduce all-cause mortality,” Andrew W. Swartz, MD, from the Yukon-Kuskokwim Delta Regional Hospital in Alaska, and colleagues wrote. “This conclusion was partially based on a meta-analysis of four randomized trials that compared flexible sigmoidoscopy screening with no screening. The meta-analysis aggregated results from the two age cohorts of one of the trials — the NORCCAP (Norwegian Colorectal Cancer Prevention) study — as if these cohorts were a single trial. Aggregation of outcomes that have markedly different event rates, screening-control ratios, or both can create a Simpson paradox.”

Swartz and colleagues reviewed the results from the NORCCAP study to determine if a Simpson paradox was created. They extracted data for all-cause mortality from the four studies used in the USPSTF evidence report. In addition, the researchers duplicated the meta-analysis using the two NORCCAP age cohorts (younger cohort, aged 50 to 54 years; older cohort, aged 55 to 64 years) as individual trials rather than a single trial to evaluate the all-cause mortality outcomes for screening flexible sigmoidoscopy. They performed a sensitivity analysis with multiple random-effects models to repeat the meta-analysis.

The researchers found that the probability of all-cause mortality was lower in the younger cohort of the NORCCAP study (RR = 0.96; 95% CI, 0.87-1.06) than the older cohort (RR = 0.98; 95% CI, 0.94-1.03). The combined summary estimate of the two cohorts had a RR of 0.98 (95% CI, 0.94-1.02). No screening was favored for all-cause mortality when the two cohorts were analyzed as a single group rather than two separate groups (RR = 1.07; 95% CI, 1.02-1.12).

However, when analyzing the cohorts as two separate groups, all-cause mortality at 11 to 12 years was reduced with flexible sigmoidoscopy (RR = 0.975; 95% CI, 0.959-0.992; P = 0.004; I² = 0%). After 11.5 years of follow-up, the absolute risk reduction of death in patients aged 50 to 74 years was three deaths per 1,000 individuals invited to screening (95% CI, 1-4.9). There were no significant changes in outcome in sensitivity analyses.

“Screening with flexible sigmoidoscopy reduces all-cause mortality with an absolute risk reduction that is clinically important relative to other preventive interventions,” Swartz and colleagues concluded. “Aggregation of outcomes of the NORCCAP study in the USPSTF evidence report created a Simpson paradox that obscured the reduction in all-cause mortality by changing two statistically nonsignificant reductions into a statistically significant increase. This effect was large enough to nullify the reductions in all-cause mortality of the other trials in the meta-analysis.”

“More than 50 years after the announcement of the first clinical trial of cancer screening, a screening method has shown a reduction in the risk for death compared with no screening,” they added. “If the primary goal of screening is to reduce the risk for death, then the evidence supporting flexible sigmoidoscopy is substantially stronger than that of other screening methods. We believe that colorectal cancer screening guidelines warrant reassessment to incorporate this evidence.” – by Alaina Tedesco

Disclosure: Swartz reports holding an unregistered copyright for a custom endoscopy image processing computer program specific to his institution. Please see full study for complete list of disclosures.