Gastrointestinal Endoscopy
Volume 71, Issue 1 , Pages 118-120, January 2010

Colonoscopy for colorectal cancer prevention: is it fulfilling the promise?

VA Outcomes Group, White River Junction VT, Department of Medicine, Dartmouth Hitchcock Medical Center, Lebanon, New Hampshire

Article Outline

Abbreviation: CRC, colorectal cancer, SEER, Surveillance Epidemiology and End Results

 

Has the increase in colonoscopy utilization over the past decade resulted in a substantial reduction in risk of colorectal cancer?

As a trainee in gastroenterology in the late 1990s, I found it hard not to be excited about the promise of colonoscopy in colorectal cancer prevention. In 1997, a multidisciplinary expert panel assembled by the U.S. Agency for Health Care Policy and Research released initial recommendations on colorectal cancer (CRC) screening and included colonoscopy every 10 years as a reasonable first option.1 In 2000, 2 landmark articles2, 3 were published describing results of screening colonoscopy. Both articles demonstrated the feasibility of screening colonoscopy and provided definitive insights into the types and locations of important advanced neoplastic lesions that would be left in situ when any technology other than colonoscopy was used. Shortly thereafter, a famous morning show anchor had a colonoscopy performed on live television that measurably increased the enthusiasm of the U.S. population for screening colonoscopy.4 Finally, the Consolidated Appropriations Act of 2001 extended the benefit of screening colonoscopy to average-risk Medicare beneficiaries.5

Those events set the stage for a dramatic increase in the performance of screening colonoscopy as it has been demonstrated by both Clinical Outcomes Research Initiative6 and Medicare5 data. Recent survey data from the Behavioral Risk Factor Surveillance System also have confirmed a move away from stool-based screening methods to lower endoscopy.7 The question, however, remains: Has the increase in colonoscopy utilization over the past decade resulted in a substantial reduction in risk of CRC?

There is some evidence that increased colonoscopy efforts are making a difference in reducing CRC disease burden. The most recent national trends in CRC incidence are encouraging. From 2002 to 2005, the annual percentage of change in death rates from CRC has decreased in both men and women by 4.3%.7 There is also evidence that CRC is being diagnosed at an earlier stage.5 Finally, for those who have normal colonoscopy findings, the rate of subsequent CRC is quite low. This was first demonstrated by using large administrative data sets.8 Most recently, a well-described population of 1256 average-risk individuals who all had normal screening colonoscopy results at baseline underwent follow-up colonoscopy approximately 5 years later, and no cancers were detected.9

However, not all the recent evidence of the effectiveness of colonoscopy has been positive. Although the occurrence of cancer after a colonoscopy with normal findings is infrequent, cancer after a colonoscopy detecting polyps seems much more common. In a recent pooled report of 9167 patients with adenomas, cancer was found after a relatively short interval in 58 patients.10 Using an algorithm to determine possible reasons for these early cancers suggested that many were preventable, likely being missed or the result of an incomplete resection of a previous lesion. Even more disturbing is the suggestion that colonoscopy may be working less effectively on the right side of the colon. One recent study using administrative data from Canada could not detect any benefit of previous colonoscopy in preventing mortality from right-sided CRC.11 Although some have suggested that this may have been a phenomenon related to the regional performance of colonoscopy outside the United States, there are data to suggest that detection of lesions on the right side may be suboptimal in this country as well. For example, Kahi12 recently reported results from a U.S. cohort of 715 patients who underwent colonoscopy in the 1980s. Seven cancers were detected during long-term follow-up, and 6 were in the ascending colon or cecum.

These recent reports highlighting potential colonoscopy “failures” are the backdrop for the current report by Leung et al13 in this issue of GIE. The article describes the long-term follow-up of patients who were participants in the Polyp Prevention Trial, a large multicenter trial of the effect of a low-fat, high-fruit and -vegetable diet on the recurrence of colorectal adenomas.14 This group previously reported cancer occurring after colonoscopy during the active treatment portion of that trial. Thirteen interval cancers were identified over 5810 person-years of observation.15 The rate of early interval cancer was certainly higher than that observed in the landmark National Polyp Study,16 but consistent with that of other reports from the Polyp Prevention Study Group17 and the Department of Veterans Affairs.18

The importance of the current article is that it reports on the long-term follow-up for cancer in this well-described (and often colonoscoped!) cohort. A total of 1297 subjects participated in this follow-up phase of the trial. During a period of approximately 6 more years, there were 9 more cases of CRC. All those with a diagnosis of cancer had undergone at least 3 colonoscopies since the original study colonoscopy (in which no cancer was found). A comparison of the observed cancer rate with that which might be expected in the general U.S. population (using Surveillance Epidemiology and End Results [SEER] registry data) was also performed. Based on the demographics of the population, 14 cancers would have been expected during follow-up and so the authors determined that repeated colonoscopic surveillance was associated with a modest nonsignificant 36% reduction in cancer incidence (standardized incidence ratio 0.64; 95% CI, 0.28-1.06). When considering the entire trial and follow-up period, the authors diagnosed 22 cancers (30 were expected), and when compared with SEER results, an even smaller 26% reduction in CRC incidence (standardized incidence ratio 0.74; 95% CI, 0.47-1.05) was seen.

Interpreting the precise decrease in cancer incidence reported here is challenging. The statistical validity of comparing this population with documented adenomas with repeated colonoscopy over time with those in whom cancer developed in the broader U.S. population (represented by SEER) is inherently problematic. Of course, this adenoma-bearing population is a high-risk one and one might expect a significantly higher rate of subsequent CRC. That being said, this population has undergone repeated colonoscopies with removal of all visualized adenomas, a practice that we think significantly decreases cancer risk. Moreover, this study population likely differs from the general U.S. population in other important ways that may bias the results in favor of finding a significant reduction in risk. For example, all subjects consented to participate in a trial to assess the effectiveness of diet in colorectal adenoma prevention and were likely more health conscious in other ways. Finally, one might expect that the quality of colonoscopy initially performed as part of a clinical trial was quite good.

Irrespective of the precise reduction in cancer risk reported in this study, the fact remains that a significant amount of ongoing cancer occurred despite repeated colonoscopy and polypectomy as necessary. So what clinical messages should be drawn from this work? First, we should strive to improve the practice of colonoscopy. Although some of these cases were likely unavoidable (eg, the result of fast growth), certainly some were potentially preventable (eg, better identification of flat colonic neoplasia). As gastroenterologists, our goal should be to strive to optimize mucosal inspection by meticulous colonic examination including adequate time for withdrawal and careful cleaning of mucosal surfaces. As investigators, we should aim to identify those factors that are associated with missed and incomplete resection of lesions and develop strategies to minimize such occurrences.

Second, these cases of interval cancer despite repeated colonoscopy remind us that we are not going to eradicate CRC with colonoscopy. The individuals found with cancer in this study had undergone at least 3 previous colonoscopies (some more), and CRC still developed. One interpretation might be that all adenoma-bearing patients require even more colonoscopic surveillance. That would likely be a mistake. There is already good evidence that the practice of surveillance is overdone,19 and it would be unfortunate if the results of an article like this drove more early surveillance in all adenoma-bearing patients.

However, there may be some subgroups of individuals with adenomas who are at particularly high risk who do merit closer follow-up. For example, in both this article and one other describing long-term follow-up in patients undergoing surveillance,20 a history of advanced adenoma at any time in the past appears to be an important risk factor for subsequent advanced adenoma formation and cancer. But for most patients with few low-risk adenomas, lengthening, not shortening, surveillance intervals is likely the best course.

Is colonoscopy fulfilling the promise? Comparative effectiveness trials will be required to definitively determine its benefit in cancer prevention and a call for such work has recently been made.21 In the absence of trials to definitively determine such effectiveness, we will need to rely on cohort data such as these to understand the performance of this procedure. Although a negative colonoscopy seems to be a fairly strong predictor of subsequent CRC-free survival, the same cannot be said for those undergoing colonoscopy with polypectomy. Careful attention to the practice of quality colonoscopy while developing strategies to better stratify adenoma-bearing patients by using either clinical epidemiology or biology will be required to further reduce the CRC burden in this population.

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Acknowledgment 

The contents of this work do not necessarily represent the views of the Department of Veterans Affairs or the United States Government.

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Disclosure 

The author disclosed no financial relationships relevant to this publication.

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References 

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PII: S0016-5107(09)02440-7

doi:10.1016/j.gie.2009.09.004

Gastrointestinal Endoscopy
Volume 71, Issue 1 , Pages 118-120, January 2010

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