Long-Term Colorectal Cancer Incidence and Mortality After Lower Endoscopy


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Colonoscopy and sigmoidoscopy have been shown to provide protection against colorectal cancer, but the magnitude and duration of protection, particularly against proximal colon cancer, remain undefined. A study of long-term colorectal cancer incidence and mortality after lower endoscopy reported in The New England Journal of Medicine by Reiko ­Nishihara, PhD, of Dana-Farber Cancer Institute and Harvard Medical School, and colleagues found that both colonoscopy and sigmoidoscopy for any indication were associated with a reduced incidence of overall colorectal cancer and distal colorectum cancer, with only colonoscopy being associated with a reduction in the incidence of proximal colon cancer.1

Screening colonoscopy and sigmoidoscopy were both associated with reduced overall colorectal cancer mortality and mortality from distal colorectum cancer, with only colonoscopy being associated with reduced mortality from proximal colon cancer.

Study Details

The study examined the association of use of lower endoscopy (updated biennially from 1988 through 2008) with colorectal cancer incidence (through June 2010) and mortality (through June 2012) among participants in the Nurses’ Health Study and the Health Professionals Follow-up Study.

Among 88,902 participants, including 31,736 men and 57,166 women, a total of 1,815 incident cases of colorectal cancer (714 in men and 1,101 in women) and 474 deaths (187 in men and 287 in women) from colorectal cancer were identified during 22 years of follow-up, representing a total of 1,738,396 person-years.

In the entire population, multivariate hazard ratios (HRs) for colorectal cancer for participants who had undergone endoscopy for any indication vs those not undergoing endoscopy were 0.57 (95% confidence interval [CI] = 0.45–0.72) after removal of adenomatous polyps, 0.60 (95% CI = 0.53–0.68) after negative sigmoidoscopy, and 0.44 (95% CI = 0.380.52) after negative colonoscopy. The findings were consistent among men and women and for all disease stages at presentation.

For distal colorectal cancer, hazard ratios were 0.40 (95% CI = 0.27–0.59) after polypectomy, 0.44 (95% CI = 0.36–0.53) after negative sigmoidoscopy, and 0.24 (95% CI = 0.18–0.32) after negative colonoscopy. Only negative colonoscopy was associated with significantly reduced risk of proximal colon cancer (HR = 0.73, 95% CI = 0.57–0.92). Findings with regard to colorectal cancer incidence were similar for screening endoscopy.

Colonoscopy Interval

Compared with no endoscopy, multivariate hazard ratios for colorectal cancer according to time since last negative colonoscopy were 0.35 (95% CI = 0.28–0.45) for an interval of ≤ 3.0 years, 0.40 (95% CI = 0.31–0.52) for 3.1 to 5.0 years, 0.52 (95% CI = 0.38–0.70) for 5.1 to 10.0 years, and 0.26 (95% CI = 0.12–0.59) for 10.1 to 15.0 years. Hazard ratios for the interval of 5.1 to 15.0 years were 0.60 (95% CI = 0.38–0.94) for proximal colon cancer and 0.35 (95% CI = 0.22–0.54) for distal colorectal cancer.

Compared with no endoscopy, participants who had undergone endoscopy with removal of adenomatous polyps had a reduced incidence of colorectal cancer with surveillance intervals of ≤ 3.0 years (multivariate HR = 0.48, 95% CI = 0.33–0.69) and 3.1 to 5.0 years (HR = 0.49, 95% CI = 0.33–0.73). Results were similar for adenomas in the proximal colon and those in the distal colorectum. For participants with high-risk adenoma, the risk reduction was smaller and of shorter duration, with a hazard ratio of 0.70 (95% CI = 0.43–1.14) for the surveillance interval of 3.1 to 5.0 years.

For colonoscopies performed at least 4 years apart, compared with no endoscopy, multivariate hazard ratios for colorectal cancer were 0.43 (95% CI = 0.35–0.51) after one negative colonoscopy, 0.32 (95% CI = 0.22–0.48) after two, and 0.23 (95% CI = 0.08–0.67) after three.

Subgroups

Colonoscopy was associated with similar significant reductions in incidence of colorectal cancer across age, body mass index, smoking status, and aspirin use subgroups. Among participants with a family history of colorectal cancer, there was no significant reduction at more than 5 years after colonoscopy (multivariate HR = 0.91, 95% CI = 0.55–1.52), with the reduction at more than 5 years remaining significant in those without a family history (HR = 0.43, 95% CI = 0.32–0.58; P = .04 for interaction).

Molecular Characteristics

A total of 62 cancers diagnosed within 5 years after colonoscopy had available molecular data. Compared with cancers diagnosed in participants more than 5 years after colonoscopy or in participants with no endoscopy, these cancers were more likely to have CpG island methylator phenotype (multivariate odds ratio [OR] = 2.19, 95% CI = 1.14–4.21), microsatellite instability (OR = 2.10, 95% CI = 1.10–4.02), and an increased LINE-1 methylation level (OR = 3.21 for each 30% increment, 95% CI = 1.29–8.00). BRAF, KRAS, and PIK3CA mutations were not significantly associated with cancer diagnosed within 5 years after colonoscopy.

Screening Endoscopy and Mortality

Compared with no screening endoscopy, colorectal cancer mortality was significantly reduced by screening sigmoidoscopy (multivariate HR = 0.59, 95% CI = 0.45–0.76) and screening colonoscopy (HR = 0.32, 95% CI = 0.24–0.45).

Screening sigmoidoscopy was associated with reduced mortality from only distal colorectum cancer (HR = 0.31, 95% CI = 0.20–0.49), whereas screening colonoscopy was associated with reduced mortality from both distal colorectal cancer (HR = 0.18, 95% CI = 0.10–0.31) and proximal colon cancer (HR = 0.47, 95% CI = 0.29–0.76).

The investigators concluded:

Colonoscopy and sigmoidoscopy were associated with a reduced incidence of cancer of the distal colorectum; colonoscopy was also associated with a modest reduction in the incidence of proximal colon cancer. Screening colonoscopy and sigmoidoscopy were associated with reduced colorectal cancer mortality; only colonoscopy was associated with reduced mortality from proximal colon cancer. Colorectal cancer diagnosed within 5 years after colonoscopy was more likely than cancer diagnosed after that period or without prior endoscopy to have [CpG island methylator phenotype] and microsatellite instability. ■

Disclosure: The study was funded by the National Institutes of Health and others.

Reference

1. Nishihara R, Wu K, Lochhead P, et al: Long-term colorectal-cancer incidence and mortality after lower endoscopy. N Engl J Med 369:1095-1105, 2013.



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