EDITORIAL
Colon adenoma surveillance: it takes a program Colon surveillance recommendations after resection of adenomas are based on several principles. First, there is evidence that individuals in whom neoplasia develops can have re-occurrence. The confluence of genetic predisposition and lifestyle risk factors probably do not change after adenomas are detected and removed; thus, the finding identifies a higher-risk individual. This is borne out in studies that demonstrate that after adenoma removal, risk of the development of more adenomas and colorectal cancer (CRC) is higher than if there are no adenomas at baseline.1 Second, we have evidence for risk stratification during surveillance.1 Individuals with advanced adenomas at their baseline colonoscopy (defined as tubular adenoma[s] 10 mm or larger or adenomas with villous histology or high-grade dysplasia) have a higher risk of having advanced neoplasia at their first surveillance examination compared with individuals with low-risk adenomas (1-2 tubular adenomas !10 mm). Recommended intervals between the baseline examination and first surveillance examination are based on this principle. Third, we have evidence that removal of adenomas reduces the subsequent risk of the development of or dying of CRC.2 Therefore, it seems intuitive that if we keep finding adenomas and removing them, we will have an impact on CRC incidence and mortality. This reasoning makes sense. However, there may appear to be some inconsistencies between what we know and what we do. For example, one might ask whether it takes many years for adenomas to develop, and if advanced adenomas (AAs) are completely removed at baseline, why do we see such high rates of AAs during surveillance at only 3 to 5 years? One hypothesis is that these individuals are predisposed to the development of new lesions quickly. Several studies have examined the biology of so-called interval CRC, occurring within 3 years of baseline colonoscopy. These studies use cancer registries to identify CRC patients, and “look back” to determine whether they had a colonoscopy within the past 6 to 36 months, in which CRC was not identified.3,4 These patients are compared with age-matched subjects with cancer diagnosed at the first colonoscopy. The interval cancers tend to be located in the proximal colon, CpG island methylation positive, with methylation and microsatellite instabilitydall
properties of the serrated polyp pathway.3,4 If these lesions progress rapidly from polyp to CRC, then some interval CRC could be related to the biology of the tumor. A second hypothesis is that polyps are incompletely removed. For many years, this was surmised because some recurrent adenomas or CRC were found in the same region of the colon where polyps were detected and removed at baseline. A recent study5 found a 10% incomplete resection rate when tissue around the polypectomy site was sampled after what was thought to be a complete polypectomy of sessile polyps. The rate of residual neoplastic tissue was even higher for larger polyps (17% for 10-20 mm polyps) and serrated polyps (31%). These data were derived from
The authors are to be commended for examining surveillance as a program rather than a one-time event.
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a study in which the endoscopist knew that his or her performance was being evaluated, so it is likely, if not probable, that rates of incomplete adenoma removal are even more common in clinical practice. If tissue is left behind, then the finding of adenomas during surveillance would be expected. Because this is more likely to happen with advanced lesions, it could partially explain the higher rate of AAs in individuals who have AAs at baseline. A third hypothesis is that lesions are missed at colonoscopy. This may be especially important if individuals have advanced adenoma(s) at baseline because the finding may identify an individual with predisposition for other lesions. If these “other” lesions are missed, they may be detected at surveillance examinations. Therefore, the quality of the baseline colonoscopy has an important impact on the findings during surveillance. Each of these factors could be important for determining appropriate intervals for surveillance. Is surveillance colonoscopy effectiveddoes it reduce CRC incidence and mortality? Alas, the data on effectiveness of surveillance are lacking. It is quite possible, that most, if not all, of the benefit of adenoma detection and removal is derived from the baseline examination. One of the reasons the data are absent is that longitudinal studies of patients enrolled in surveillance programs are few in number. The only way that we are ultimately going
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to understand the benefits and risks of surveillance is to think about it programmatically and ask “can we identify high-risk individuals over the course of several examinations and select these individuals for more frequent intensive surveillance?” Conversely, can we identify the low-risk patients who do not need frequent examinations? Imperiale et al6 tackle this important question in this issue of Gastrointestinal Endoscopy. What do we know about surveillance “programs”? Three previous studies performed longitudinal follow-up of adenoma-bearing patients and revealed some consistent results.7-9 Individuals who have 1 or more advanced lesions either at baseline or surveillance 1 continue to have a higher risk of having advanced lesions at surveillance 2, a finding strongly supported by the results from Imperiale et al.6 In the current study, the authors follow patients through 2 rounds of surveillance. They propose a risk model that includes age plus findings at baseline and surveillance 1 to identify low-risk persons for whom intervals between the first and second surveillance might be extended. Based on their data, the impact of age at surveillance 1 is a predictor of risk (odds ratio: 1.47) (but not at surveillance 2), whereas the finding of AAs is very strongly associated with higher risk (odds ratio: 3.18). These data would seem to support a program of continued intense surveillance for individuals with AAs at surveillance 1 and are consistent with previous work. Does the addition of age as a variable in the risk model add much? Based on the proposed risk model, it would appear that a younger individual (younger than 60 years of age) with advanced neoplasia at both baseline and surveillance 1 would fall into the low-risk group with a score of 4 or 5. I think most clinicians would be reluctant to extend intervals for such patients. Although age may be a risk factor for finding AAs during surveillance, the findings of baseline and surveillance 1 appear to be much stronger factors. We must also acknowledge that there may be other CRC risk factors that could influence the natural history of colon neoplasia not considered in this index score, a point acknowledged by Imperiale et al.6 We know that use of nonsteroidal anti-inflammatory drugs (NSAIDs) may be chemopreventive, such that individuals taking aspirin or NSAIDs may have a lower risk of adenomas at 3 years after baseline colonoscopy and polypectomy. Other CRC risk modulators include smoking, heavy alcohol, body mass index, physical activity, diet, race, and ethnicity. Could these factors affect the risk of AAs during a program of surveillance? We do not know. Tao et al10 recently evaluated a more comprehensive set of risk factors to predict finding AAs at the baseline screening examination, which included smoking, alcohol, diet, and NSAIDs. Another area of uncertainty in surveillance programs is the quality of colonoscopy. Should the risk index be
modified for large polyps (O10 mm) or serrated polyps because of the higher rate of incomplete removal?5 Should the risk index be modified if the prep is fair, and small polyps might be missed? Further work is needed (as the authors suggest) to refine this risk index. The authors are to be commended for examining surveillance as a program rather than a one-time event. An important message from this article is the finding of one or more AAs during surveillance is a strong indicator of risk of subsequent AAs, a finding that corroborates data from earlier studies. This is an important contribution that helps inform guidelines for surveillance programs. Further validation of the index score is warranted as the authors suggest. Given the importance of quality on surveillance (missed lesions and incompletely removed lesions), future attempts at risk prediction should include some measures of quality, including bowel prep quality, completeness of examination to the cecum, and the likelihood of complete polyp removal. For example, we may find that larger sessile serrated polyps, which are more likely to be incompletely removed at baseline, should be weighted in any risk-scoring scheme. In contrast, individuals with large pedunculated polyps may end up having a low risk of subsequent AAs because they are more likely to be completely removed at baseline. In addition, in future efforts at risk stratification, other possible risk modulators might be considered such as NSAID use, smoking status, body mass index, race, and ethnicity, factors that could be more important than age alone.
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DISCLOSURE The author disclosed no financial relationship relevant to this article. David Lieberman, MD Division of Gastroenterology and Hepatology Oregon Health and Science University Portland, Oregon, USA Abbreviations: AA, advanced adenoma; CRC, colorectal cancer; NSAID, nonsteroidal anti-inflammatory drug.
REFERENCES 1. Lieberman DA, Rex DK, Winawer SJ, et al. Guidelines for colonoscopy surveillance after screening and polypectomy: a consensus update by the US Multi-Society Task Force on Colorectal Cancer. Gastroenterology 2012;143:844-57. 2. Zauber AG, Winawer SJ, O'Brien MD, et al. Colonoscopic polypectomy and long-term prevention of colorectal-cancer deaths. N Engl J Med 2012;366:687-96. 3. Arain MA, Sawhney M, Sheikh S, et al. CIMP status in interval colon cancer: another piece to the puzzle. Am J Gastroenterol 2010;105:1189-95. 4. Nishihara R, Wu K, Lochhead P, et al. Long-term colorectal cancer incidence and mortality after lower endoscopy. N Engl J Med 2013;369: 1095-105.
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5. Pohl H, Srivastava A, Bensen SP, et al. Incomplete polyp resection duri9ng colonoscopy–results of the complete adenoma resection (CARE) study. Gastroenterology 2013;144:74-80. 6. Imperiale TF, Juluri R, Sherer EA, et al. A risk index for advanced neoplasia on the second surveillance colonoscopy in patients with previous adenomatous polyps. Gastrointest Endosc 2014;80: 471-8. 7. Laiyemo AO, Pinsky PF, Marcus PM, et al. Utilization and yield of surveillance colonoscopy in the continued follow-up study of the Polyp Prevention Trial. Clin Gastroenterol Hepatol 2009;7:562-7.
8. Robertson DJ, Burke CA, Welch G, et al. Using the results of a baseline and a surveillance colonoscopy to predict recurrent adenomas with high-risk characteristics. Ann Intern Med 2009;151:103-9. 9. Pinsky PF, Schoen RE, Weissfeld JL, et al. The yield of surveillance colonoscopy by adenoma history and time to examination. Clin Gastroenterol Hepatol 2009;7:86-92. 10. Tao S, Hoffmeister M, Brenner H. Development and validation of a scoring system to identify individuals at high risk for advanced colorectal neoplasms who should undergo colonoscopy screening. Clin Gastroenterol Hepatol 2014;12:478-85.
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