We previously found that polypectomy reduced the incidence of colorectal cancer in the NPS cohort.5
The present study suggests that adenoma removal significantly reduced the risk of death from colorectal cancer, as compared with that in the general population, and in the first 10 years after polypectomy, reduced the risk to a level similar to that in an internal concurrent control group of patients with no adenomas.
Our comparison of observed deaths in the adenoma cohort with expected deaths in the general population, based on SEER data that were specific for age, sex, race, and calendar year, may have underestimated the reduction in mortality that may be achieved with colonoscopic polypectomy in screening populations. Because all the patients in the adenoma cohort had adenomas, including 57.3% with advanced adenomas, they represented a higher-risk group than the general population.25-27
The comparison of mortality in the adenoma cohort with that in a concurrent control group of patients in the NPS who did not have adenomatous polyps supported the results of the comparison with estimated mortality in the general population.6
The patients without adenomas were similar to those with adenomas, except for the findings at initial colonoscopy. The group without a precursor adenoma would be expected to have low mortality from colorectal cancer, and several studies have also shown that patients with no polyps or with nonadenomatous polyps have low rates of colorectal neoplasia after colonoscopy.28-31
A cohort of patients with adenomas in whom polypectomy was not performed would, of course, be a more meaningful comparison group for the patients in the NPS with adenomas, all of whom underwent polypectomy, but such a comparison group would not be an option on either ethical or clinical grounds because of the known potential for adenomas to progress to carcinoma. We addressed this comparison using a microsimulation model of the mortality effect had the adenomas not been removed and the natural history of the adenoma–carcinoma sequence had proceeded without intervention. This model, the MISCAN-Colon model of the Cancer Intervention and Surveillance Modeling Network (CISNET) (http://cisnet.cancer.gov/colorectal
), showed an even larger reduction in mortality from polypectomy than the comparison with the SEER incidence-based mortality rates (see the Supplementary Appendix
Although the NPS does not address the effectiveness of screening colonoscopy in the general population, our findings provide an indirect estimate of the effect of removing adenomas, which is the primary interventional measure in screening colonoscopy. Studies and commentaries have raised issues regarding the magnitude of the effect of colonoscopy on the incidence of and mortality from colorectal cancer.32-38
A recent study from Germany showed a large effect of colonoscopy on the incidence of colorectal cancer.39
In two Canadian studies,32,34
the mortality reduction from colonoscopy in community practice was largest when the colonoscopy was performed by a gastroenterologist34
and when the examination was complete.32
The magnitude of the reduction in mortality among the patients in the NPS after polypectomy is probably due to high-quality colonoscopy performed by well-trained gastroenterologists.40-45
These issues will be more precisely understood after completion of long-term randomized, controlled trials of screening colonoscopy in the general population that have recently been initiated in northern Europe (Nordic-European Initiative on Colorectal Cancer; ClinicalTrials.gov number, NCT00883792
in Spain (ClinicalTrials.gov number, NCT00906997
), and by the Veterans Administration in the United States (ClinicalTrials.gov number, NCT01239082
); the incidence and mortality end points will not be available for at least 10 or more years.
This prospective study has some limitations. First, a small number of trained endoscopists performed the colonoscopies according to a study protocol that required examination to the cecum, adequate preparation, careful inspection of the colon, and removal of all identified polyps, features that are consistent with reports of high-quality performance.40-42
Consequently, the NPS observations may not be generalizable to present community practice, for which reported incidence rates of colorectal cancer after polypectomy are higher than those reported in the NPS.47,48
Comparisons with mortality from colorectal cancer in the general population, based on the SEER data, were limited by our inability to adjust for differences between the NPS cohort and the general population in risk factors, behaviors, access to health care, or quality of health care. All-cause mortality was lower for the patients enrolled in the NPS than for the general population; the difference may be attributable to better access to medical care (which included colonoscopy) in the NPS study and the fact that the study patients were in sufficiently good health (especially with respect to cardiovascular disease)49
to have been referred for colonoscopy during the period from November 1980 through February 1990.
Our comparison of the two NPS cohorts (patients with and those without adenomas) was limited by the very small number of deaths from colorectal cancer, as reflected by the wide confidence intervals, indicating either a large decrease or a large increase in the relative risk of death from colorectal cancer for the patients with adenomas, as compared with those with only nonadenomas.
An additional limitation of the study is that it did not take account of potential changes in life-style over time. After detection and removal of an adenoma, patients may stop smoking, modify their diet, control their weight, increase their physical activity, and take multivitamins and nonsteroidal antiinflammatory drugs15,50-53
to prevent recurrence of adenomas and prevent colorectal cancer.
Deaths that occurred during the study were ascertained with the use of data from the NDI. These data are based on information from death certificates, which do not include the site in the colorectum of the original cancer. Consequently, mortality rates associated with proximal and distal cancers could not be compared in this study.24
Finally, 81% of the patients in the randomized adenoma cohort underwent surveillance colonoscopies after polypectomy.9
Consequently, the polypectomy effect for these patients would include the effect of surveillance colonoscopies as well.54
In conclusion, we previously reported a lower-than-expected incidence of colorectal cancer in patients after the removal of adenomatous polyps,5
and this study shows that polypectomy results in reduced mortality from colorectal cancer. These combined findings indicate that adenomas identified and removed at colonoscopy include those that are clinically important, with the potential to progress to cancer and cause death. A demonstrated reduction in mortality with colonoscopic polypectomy is a critical prerequisite for continued recommendations of screening colonoscopy in clinical practice while we wait for the results of randomized, controlled trials of screening colonoscopy.