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Long-Term Colorectal Cancer Mortality After Removal of Adenomas

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Key Points

  • Risk of long-term colorectal cancer mortality was evaluated in patients after adenoma removal vs the general population.
  • Removal of high-risk adenomas was associated with a 16% increase in risk of colorectal cancer mortality
  • Removal of low-risk adenomas was associated with a 25% decrease in risk of colorectal cancer mortality.
  • Frequent colonoscopic surveillance may be unnecessary after removal of low-risk adenomas.

There are few data available on long-term risk of colorectal cancer mortality after adenoma removal. In a Norwegian study reported in The New England Journal of Medicine, Løberg et al found that patients who had low-risk adenomas removed had lower colorectal cancer mortality risk and those who had high-risk adenomas removed had higher colorectal cancer mortality risk compared with the general population over 7.7 years of follow-up. The findings suggest that frequent colonoscopic surveillance may be unnecessary after removal of low-risk adenomas.

Study Details

In the study, the linked Cancer Registry and Cause of Death Registry of Norway were used to estimate colorectal cancer mortality among patients who underwent removal of colorectal adenomas between 1993 and 2007 and who were followed through 2011. Incidence-based standardized mortality ratios (SMRs) were generated using colorectal cancer mortality rates for the Norwegian general population. Polyp size and exact number were not available from the cancer registry. High-risk adenomas were defined as multiple adenomas or adenomas with a villous component or high-grade dysplasia.

Current Norwegian guidelines recommended colonoscopy after 10 years for patients with high-risk adenomas (eg, those with high-grade dysplasia, a villous component, or a size ≥ 10 mm) and after 5 years for patients with three or more adenomas, with no surveillance recommended for those with low-risk adenomas.

Risk Characterization

A total of 40,826 patients who had undergone removal of colorectal adenomas were identified, including 23,449 (51.3%) with removal of low-risk adenomas and 22,306 (48.8%) with removal of high-risk adenomas, including at least two adenomas (22.8%), villous or tubulovillous growth pattern adenomas (28.8%), and adenomas with high-grade dysplasia (15.3%). Review of detailed pathology reports for 442 patients, however, showed that 8.2% of 220 patients with adenomas classified as high-risk had low-risk adenomas and that 30.2% of those with adenomas characterized as low-risk had high-risk adenomas.

Colorectal Cancer Mortality Risks

Median follow-up was 7.7 years (maximum 19.0 years). Overall, 1,273 patients (387 per 100,000 person-years) were diagnosed with colorectal cancer; 383 (115/100,000 person-years) died of colorectal cancer compared with 398 expected colorectal cancer deaths in the general population (SMR = 0.96, 95% confidence interval [CI] = 0.87–1.06). Overall, compared with the general population, colorectal cancer mortality among those with adenomas removed was reduced among men (SMR = 0.86, 95% CI = 0.74–1.00) but not among women (SMR = 1.06, 95% CI = 0.93–1.22).

Compared with colorectal cancer mortality in the general population, colorectal cancer mortality was significantly increased among patients with high-risk adenomas removed (242 observed deaths vs 209 expected deaths, SMR = 1.16, 95% CI = 1.02–1.31) and significantly decreased among patients with low-risk adenomas removed (141 observed deaths vs 189 expected deaths, SMR = 0.75, 95% CI = 0.63–0.88). Overall, patients who were diagnosed with colorectal cancer before 2000 had a higher risk of colorectal cancer death than those diagnosed after 2000. 

Factors Associated With Mortality

On multivariate analysis of colorectal cancer mortality including age, sex, number of adenoma occurrences, period of adenoma removal, adenoma location, number of adenomas, grade of dysplasia, and growth pattern, first adenoma removal in the 2000s (hazard ratio [HR] = 0.63, P < .001, vs 1990s) was associated with reduced mortality. Factors associated with increased mortality included multiple adenomas (HR = 1.31, P = .02), villous growth pattern (HR = 1.40, P = .002), and high-grade dysplasia (HR = 1.45, P = .002), as well as increased age at first adenoma removal (HRs = 2.43–17.74, P ≤ .01, for older age groups vs 40–49 year group).

The investigators concluded: “After a median of 7.7 years of follow-up, colorectal-cancer mortality was lower among patients who had had low-risk adenomas removed and moderately higher among those who had had high-risk adenomas removed, as compared with the general population…. Our finding that the removal of low-risk adenomas reduces the risk of death from colorectal cancer over a period of 8 years to a level below the risk in the general population is consistent with the hypothesis that surveillance every 5 years after removal of low-risk adenomas may confer little benefit over less intensive surveillance strategies. Furthermore, complications associated with colonoscopy are not trivial and might offset the benefit of surveillance….”

Magnus Løberg, MD, and Mette Kalager, MD, PhD, of University of Oslo, contributed equally to The New England Journal of Medicine article.

The study was funded by the Norwegian Cancer Society and others. For full disclosures of the study authors, visit www.nejm.org.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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