Volume 7, Issue 7 , Pages 714-715, July 2009
Is Screening Colonoscopy Effective in Preventing Cancer? Some Answers, More Questions
Article Outline
Understanding colonoscopy's effectiveness in colorectal cancer (CRC) prevention remains a critically important question to patients, endoscopists, and policy makers. Colonoscopy screening to prevent CRC is widely recommended by high profile groups1, 2 providing recommendations, and there is good evidence that the message is being heeded. Use of lower endoscopy for screening increased from 45% of the US population in 2002 to 56% in 2006. Given this increase in utilization, just how much benefit are we getting?
There is indirect evidence that CRC screening efforts might be making a difference. A recent national report analyzed trends in CRC incidence and mortality.3 From 1998 to 2005, CRC incidence has decreased by 2.2% in women and 2.8% in men. It is tempting to ascribe the observed benefit to enhanced screening efforts particularly by colonoscopy because that is becoming the dominant modality in the US. However, such assumptions should be made cautiously. Other factors have also changed over time and might account for the encouraging trends. The use of pharmacologic agents such as statins has also grown dramatically in recent years. Some studies would suggest that the benefit of such products on CRC incidence might not be trivial, up to a 50% reduction with long-term statin use in one study.4 Therefore, although ecologic observations relating cancer screening and declines in CRC can suggest benefit, more direct evidence is needed.
To that end, in this issue Kahi et al5 report a long-term follow-up study of average risk individuals initially screened about 20 years ago at Indiana University–Purdue University at Indianapolis. At that time, 17,000 physicians, dentists, nurses, and their spouses were invited to undergo screening colonoscopy. Individuals with a personal history of high risk conditions (eg, history of adenoma formation or inflammatory bowel disease) or a strong family history of cancer were excluded. For this analysis the investigators examined whether CRC was subsequently diagnosed by the combination of medical record review and phone contact. If the patient had died, efforts were made to contact the next of kin to understand the cause of death. To provide context, the observed rates of CRC incidence and mortality were compared with those that would be expected for age, sex, and calendar matched individuals in the general population.
The results suggest that screening colonoscopy had a significant beneficial effect, reducing CRC incidence and mortality. In total, 12 cancers (5 at the time of the initial colonoscopy and 7 subsequently) were identified during 10,492 person-years of follow-up. On the basis of population controls, 23 cancers would have been expected (standardized incidence ratio, 0.52; 95% confidence interval [CI], 0.22–0.82) during that period of observation. Although underpowered to look at mortality, the results were still encouraging. Only 3 patients died of CRC, when the expected number would have been 9 (standardized mortality ratio, 0.35; 95% CI, 0.0–1.06).
The study has some important strengths. First, it follows a “mixed” population of patients, some with normal colonoscopy at baseline and others with adenomas. Most studies to date have reported risk in either those with a negative colonoscopy or those with a history of adenoma removal. Therefore, this study better represents the type of patients followed if universal colonoscopy screening were more generally applied. Second, the size of the cohort is relatively large and the follow-up period is long (up to 18 years) as to be informative. Most importantly, the follow-up of these patients is virtually complete. In fact, follow-up information was available on 97% of the patients in the original cohort; therefore, few important outcomes (ie, cancer) should have been missed.
Taken in total, this study goes into a growing pile of articles that suggest colonoscopy is effective in reducing both CRC incidence and mortality. On the basis of this report, should we reasonably assume that screening colonoscopy, if more universally applied, would reduce cancer incidence (48%) and mortality (65%) by the amount seen here? Probably not. This is likely a “best case scenario” for a number of reasons related to the nature of the assembled cohort. To enter the study, one had to be either a health professional or married to one. Almost certainly, the doctors and nurses responding to this invitation were health-conscious (hence their desire for a screening colonoscopy when it was not nearly as fashionable as today). We know nothing about important confounders to the observed association such as body mass index or exercise that likely bias the estimates in favor of benefit. Similarly, aspirin intake might also be an important unmeasured confounder. We know from randomized trials that aspirin reduces the risk of colorectal neoplasia.6, 7 Interestingly, the Physicians Health Study, which showed that an aspirin per day reduces risk of myocardial infarction by 50%, was published the same year this study began recruitment!8 Almost assuredly, the health professionals in this study were more likely to take daily aspirin and engage in other health-promoting behaviors as compared with an average person in the population and favorably influenced the observed cancer rates.
Second, the population under study was largely (95%) white. We know that there are differences in the behavior of CRC when comparing African Americans and whites.9 For example, African Americans have a higher incidence of CRC and lower survival. There is also a possibility of more proximal distribution of neoplasia in African Americans. Although the reported incidence rates were standardized for age and gender, they were not standardized for race. In short, if screening is just not as effective in non-white populations, real-world performance of the test might be different than what was observed here.
Finally, the single center nature of the report might affect the generalizabilty of the results to everyday practice. In their discussion, the authors suggest that the effectiveness of colonoscopy with polypectomy observed in the National Polyp Study10 might be better than that observed in other cohorts because the exams in the National Polyp Study were performed by “experts.” Certainly the performance of colonoscopy in this report, based at a university interested in studying screening colonoscopy, was likely quite good. In fact, the article's senior author is recognized as one of the world experts in colonoscopy and likely performed a significant number of the exams. Factors related to the local expertise at this center are hard to measure, but they likely bias the report in favor of benefit.
So the question remains: how good is colonoscopy in cancer prevention? In truth, there seems to be 2 important factors influencing the results drawn from current studies. First, colonoscopy seems to work best when nothing is done. In fact, most (about 75%) participants in the current study had a negative colonoscopy, and there is growing evidence that the observed cancer rate in such populations is low. There are 2 large Canadian studies11, 12 that used administrative data in individuals undergoing a “negative” colonoscopy (ie, no code for biopsy or polypectomy). The 10-year CRC-free survival in these cohorts is quite good, with a reduction in observed cancer incidence ranging from 50% to 70%. Most recently, Imperiale et al13 reported 5-year follow-up of a cohort (n = 1256) with a negative baseline screening colonoscopy, and no cancers were detected.
However, rates of early interval cancers appear to be significantly higher in those with a history of adenoma. We recently reported interval cancers in 9000 subjects who are part of a large pooled cohort of patients, all of whom had 1 or more adenomas at baseline.14 After approximately 4 years of follow-up, 58 cancers were observed, an absolute rate that is obviously far greater than that observed by Imperiale et al.13 Whether these cancers are simply missed lesions or the result of rapid growth is not entirely clear. However, if we are going to continue to justify colonoscopy and polypectomy at the rates with which they are being performed, we should strive to do better in reducing subsequent cancer risk in the adenoma-bearing patients. If colonoscopy's main role in screening is to identify low risk groups unlikely to develop cancer (ie, those with a negative colonoscopy), then colonoscopy runs the risk of being replaced by noninvasive technologies that might equivalently isolate low risk populations without the need for a sedated invasive exam.
The second important factor influencing colonoscopy's observed effectiveness in cancer prevention pertains to the side of the colon being evaluated. Not many years ago, Podolsky15 somewhat famously commented that flexible sigmoidoscopy was the equivalent of mammography of one breast. There is good evidence that sigmoidoscopy is effective at reducing CRC incidence on the left side, and it was assumed that colonoscopy would yield benefits throughout the colon. However, a recent case-control study with administrative data showed that exposure to complete colonoscopy was associated with a 67% reduction in left-sided cancer (0.23; 95% CI, 0.28–0.39) but essentially no reduction in right-sided cancer (0.99; 95% CI, 0.86–1.14). In this light, it is somewhat disturbing that 6 of the 7 cancers that were detected after baseline colonoscopy in the current study were at or proximal to the hepatic flexure. Others have commented as to the cause(s) of colonoscopy's failure on the right side of the colon. Whether the problem is more correctable (eg, prep related) or less so (fast growth on the right) remains to be determined. Whatever the cause, if colonoscopy is to remain the preferred screening modality, this important issue will have to be successfully addressed. To extend the mammogram analogy above, it might not be justifiable to continue to image both the right and left breasts, if cancer can only be prevented on the left!
Therefore, although the results of the current article are encouraging, there is still considerable work to be done. In the right population and in the right hands the technology likely works well, and the current article demonstrates that. However, further work is needed to more accurately assess whether widespread performance of colonoscopy can yield significant benefits in cancer prevention on both sides of the colon and in diverse and adenoma-bearing populations. If colonoscopy is not fully succeeding in these areas, efforts to improve technical performance are warranted.
References
- Screening for colorectal cancer: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med. 2008;149:627–637
- Screening and surveillance for the early detection of colorectal cancer and adenomatous polyps, 2008: a joint guideline from the American Cancer Society, the US Multi-Society Task Force on Colorectal Cancer, and the American College of Radiology. Gastroenterology. 2008;134:1570–1595
- Annual report to the nation on the status of cancer, 1975-2005, featuring trends in lung cancer, tobacco use, and tobacco control. J Natl Cancer Inst. 2008;100:1672–1694
- Statins and the risk of colorectal cancer. N Engl J Med. 2005;352:2184–2192
- Effect of screening colonoscopy on colorectal cancer incidence and mortality. Clin Gastroenterol Hepatol. 2009;7:770–775
- A randomized trial of aspirin to prevent colorectal adenomas. N Engl J Med. 2003;348:891–899
- A randomized trial of aspirin to prevent colorectal adenomas in patients with previous colorectal cancer. N Engl J Med. 2003;348:883–890
- . Final report on the aspirin component of the ongoing Physicians' Health Study. N Engl J Med. 1989;321:129–135
- Colorectal cancer in African Americans. Am J Gastroenterol. 2005;100:515–523discussion 514
- Prevention of colorectal cancer by colonoscopic polypectomy: the National Polyp Study Workgroup. N Engl J Med. 1993;329:1977–1981
- Risk of developing proximal versus distal colorectal cancer after a negative colonoscopy: a population-based study. Clin Gastroenterol Hepatol. 2008;6:1117–1121quiz 1064
- Risk of developing colorectal cancer following a negative colonoscopy examination: evidence for a 10-year interval between colonoscopies. JAMA. 2006;295:2366–2373
- Five-year risk of colorectal neoplasia after negative screening colonoscopy. N Engl J Med. 2008;359:1218–1224
- Interval cancer after total colonoscopy: results from a pooled analysis of eight studies. Gastroenterology. 2008;134:A-111–A-112
- . Going the distance: the case for true colorectal-cancer screening. N Engl J Med. 2000;343:207–208
Conflicts of interest The author discloses no conflicts.
PII: S1542-3565(09)00320-6
doi:10.1016/j.cgh.2009.03.028
© 2009 AGA Institute. Published by Elsevier Inc. All rights reserved.
Volume 7, Issue 7 , Pages 714-715, July 2009
