Flexible Sigmoidoscopy Reduces Incidence of Colorectal Cancer

The use of flexible sigmoidoscopy as a screening tool significantly reduced the overall mortality associated with colorectal cancer by 26% and its incidence by 21%, according to results of a recent study [N Engl J Med. 2012; 10.1056/NEJMoa1114635]. The study focused particularly on the effect of flexible sigmoidoscopy on the incidence of, and mortality associated with, distal and proximal colorectal cancer.

Screening via flexible sigmoidoscopy or colonoscopy is more sensitive than fecal testing to detect adenomatous polyps, the precursor to colorectal cancer, which has become the second leading cause of cancer-related deaths in the United States. The multicenter, randomized study known as the PLCO (Prostate, Lung, Colorectal, and Ovarian) Cancer Screening Trial enrolled 154,900 men and women 55 to 74 years of age between 1993 and 2001, and evaluated flexible sigmoidoscopy versus usual care (fecal occult-blood testing). A total of 77,445 participants were randomly assigned to flexible sigmoidoscopy (intervention group) and 77,455 to usual care.

Participants in the intervention group were offered flexible sigmoidoscopy at baseline and then again at 3 or 5 years, and were requested to complete annual questionnaires. Information such as cancer incidence, stage, and location were verified from medical records. A screening-detected cancer was defined as a colorectal cancer diagnosed within 1 year of flexible sigmoidoscopy. The primary end point of the study was death from colorectal cancer; secondary end points included colorectal cancer incidence, cancer stage, survival, harms of screening, and all-cause mortality. Between-group differences in mortality were assessed using a weighted log-rank test.

Baseline characteristics between the 2 groups were similar and the mean follow-up time was 11 years. Among the total participants in the intervention group, 83.5% underwent baseline screening and 54% underwent subsequent screening at 3 or 5 years. Results showed the incidence of colorectal cancer was 11.9 cases per 10,000 person-years (1012 cases) compared with 15.2 cases per 10,000 person-years for the usual-care group (1287 cases), translating to a 21% reduction (relative risk [RR], 0.79; 95% CI, 0.72-0.85; P<.001).

Distal cancer was reduced in the intervention group by 29% (479 cases vs 669 cases in the usual-care group [RR, 0.71, 95% CI, 0.64-0.80; P<.001]). Proximal cancer was also reduced in the intervention group by 14% (512 cases vs 595 cases in the usual-care group [RR, 0.86; 95% CI, 0.76-0.97; P=.01]). There was a borderline significant interaction between sex and study-group assignment; the RR of colorectal cancer was 0.73 for men (95% CI, 0.66-0.82) and 0.86 for women (95% CI, 0.76-0.98; P=.052). Reduction in incidence was similar across age groups: 0.78 (95% CI, 0.69-0.87) for those 55 to 64 years of age and 0.79 (95% CI, 0.71-0.89) for those 65 to 74 years of age.

Mortality related to colorectal cancer was 2.9 per 10,000 person-years in the intervention group (252 deaths) compared with 3.9 per 10,000 person-years in the usual-care group (341 deaths), which represented a 26% reduction (RR, 0.74; 95% CI, 0.63-0.87; P<.001). The researchers found mortality associated with distal colorectal cancer was reduced by 50% (RR, 0.50; 95% CI, 0.38-0.64; P<.001) although mortality related to proximal colorectal cancer was not affected.

In addition, men experienced a 34% reduction in colorectal cancer mortality compared with 13% for women (RR, 0.66; 95% CI, 0.53-0.81 vs 0.87; 95% CI, 0.68-1.12, respectively). The RR for mortality among participants 55 to 64 years of age was 0.84 (95% CI, 0.67-1.06) and for those 65 to 74 years of age, 0.65 (95% CI, 0.52-0.82; P=.11 for the interaction between age and study-group assignment).

Cancers detected by screening comprised 24.1% (244/1012) of colorectal cancers in the intervention group, and were more likely to be early stage (I or II) compared with those who were never screened or whose tumors were not detected by screening (75.4% vs 50.9% and 50.7%, respectively; P<.001 for both comparisons).