Post-Polypectomy Surveillance That Would Please Goldilocks—Not Too Much, Not Too Little, but Just Right

As colorectal cancer (CRC) screening use increases worldwide1Schreuders E.H. Ruco A. Rabeneck L. et al.Colorectal cancer screening: a global overview of existing programmes.Gut. 2015; 64: 1637-1649Crossref PubMed Scopus (717) Google Scholar and as endoscopists, armed by ever more high-definition colonoscopes, are exhorted to increase their adenoma and serrated adenoma detection rates,2Corley D.A. Jensen C.D. Marks A.R. et al.Adenoma detection rate and risk of colorectal cancer and death.N Engl J Med. 2014; 370: 1298-1306Crossref PubMed Scopus (1166) Google Scholar, 3Kahi C.J. Hewett D.G. Norton D.L. et al.Prevalence and variable detection of proximal colon serrated polyps during screening colonoscopy.Clin Gastroenterol Hepatol. 2011; 9: 42-46Abstract Full Text Full Text PDF PubMed Scopus (341) Google Scholar, 4East J.E. Vieth M. Rex D.K. Serrated lesions in colorectal cancer screening: detection, resection, pathology and surveillance.Gut. 2015; 64: 991-1000Crossref PubMed Scopus (80) Google Scholar the number of individuals funneled into surveillance colonoscopy will grow considerably. Surveillance now accounts for approximately 20% of the US colonoscopy volume,5Lieberman D.A. Williams J.L. Holub J.L. et al.Colonoscopy utilization and outcomes 2000 to 2011.Gastrointest Endosc. 2014; 80: 133-143Abstract Full Text Full Text PDF PubMed Scopus (83) Google Scholar but most essential questions about surveillance remain unanswered. Who benefits from surveillance? At what frequency should surveillance be performed? What is the relative benefit of surveillance versus initial screening? Despite decades of colonoscopy use, the data on surveillance practice and yield are surprisingly sparse. Community-based studies show that surveillance is often overused in subjects with negative screening examinations and nonadvanced adenomas, and underused in subjects with advanced adenoma.6Schoen R.E. Pinsky P.F. Weissfeld J.L. et al.Utilization of surveillance colonoscopy in community practice.Gastroenterology. 2010; 138: 73-81Abstract Full Text Full Text PDF PubMed Scopus (173) Google Scholar, 7Lieberman D.A. Holub J.L. Morris C.D. et al.Low rate of large polyps (>9 mm) within 10 years after an adequate baseline colonoscopy with no polyps.Gastroenterology. 2014; 147: 343-350Abstract Full Text Full Text PDF PubMed Scopus (25) Google Scholar Recent studies from the Netherlands8van Heijningen E.M. Lansdorp-Vogelaar I. Steyerberg E.W. et al.Adherence to surveillance guidelines after removal of colorectal adenomas: a large, community-based study.Gut. 2015; 64: 1584-1592Crossref PubMed Scopus (70) Google Scholar and Italy9Zorzi M. Senore C. Turrin A. et al.Appropriateness of endoscopic surveillance recommendations in organised colorectal cancer screening programmes based on the faecal immunochemical test.Gut. 2015; (21:2015–310139)Crossref Scopus (187) Google Scholar confirm significant numbers of inappropriate recommendations for surveillance colonoscopy. Large-scale trials in the 1990s and 2000s that focused on screening with guaiac-based fecal occult blood testing or flexible sigmoidoscopy established that screening lowers CRC incidence and mortality. Trials currently underway are evaluating screening colonoscopy compared to usual care10Kaminski M.F. Bretthauer M. Zauber A.G. et al.The NordICC Study: rationale and design of a randomized trial on colonoscopy screening for colorectal cancer.Endoscopy. 2012; 44: 695-702Crossref PubMed Scopus (137) Google Scholar or to a program of repeated fecal immunochemical testing.11Robertson D.J. Kaminski M.F. Bretthauer M. Effectiveness, training and quality assurance of colonoscopy screening for colorectal cancer.Gut. 2015; 64: 982-990Crossref PubMed Scopus (50) Google Scholar What to do after preneoplastic polyps are removed at colonoscopy is an understudied frontier that needs attention. Surveillance can be defined as testing asymptomatic persons at increased risk for colorectal neoplasia owing to a previous history of neoplasia. Surveillance colonoscopy is performed to mitigate or prevent subsequent CRC incidence and mortality. CRC diagnosed after colonoscopy is often termed “interval cancer.” By consensus, interval CRCs are defined as “colorectal cancer diagnosed after a colorectal screening examination or test in which no cancer is detected, and before the date of the next recommended exam.”12Sanduleanu S. le Clercq C.M. Dekker E. et al.Definition and taxonomy of interval colorectal cancers: a proposal for standardising nomenclature.Gut. 2015; 64: 1257-1267Crossref PubMed Scopus (128) Google Scholar Not all occurrences of CRC subsequent to colonoscopy are modifiable by surveillance. For example, the current US Multisociety Task Force (USMSTF) guideline for surveillance advises a repeat colonoscopy at 5–10 years after removal of 1 or 2 nonadvanced adenomas.13Lieberman D.A. Rex D.K. Winawer S.J. 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: 844-857Abstract Full Text Full Text PDF PubMed Scopus (1425) Google Scholar CRCs that occur before the first potential scheduled surveillance colonoscopy examination, that is before year 5 (regardless of whether owing to a missed prevalent CRC, a missed or incompletely resected adenoma or serrated lesion, or new, rapidly progressive neoplasia), are interval CRCs that are not preventable by surveillance. In contrast, CRCs that occur between years 5 and 10 could possibly be prevented or detected early by surveillance at year 5. There is a pressing need for clinical trials to evaluate surveillance intervals. One such trial, the randomized European POlyp Surveillance trial (EPOS) is just beginning. In this trial, subjects with low-risk adenomas will be randomized to surveillance at 5 and 10 years versus surveillance at 10 years, and subjects with high-risk adenomas will be randomized to surveillance at 3 and 5 years versus surveillance at 5 years. The trial will also include an observational study of the yield of surveillance colonoscopy after detection of serrated lesions. Conflicting guideline recommendations for surveillance issued by various professional societies are longstanding and global differences persist. Contrasts between the USMSTF,13Lieberman D.A. Rex D.K. Winawer S.J. 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: 844-857Abstract Full Text Full Text PDF PubMed Scopus (1425) Google Scholar European,14Atkin W.S. Valori R. Kuipers E.J. et al.European guidelines for quality assurance in colorectal cancer screening and diagnosis. First edition–colonoscopic surveillance following adenoma removal.Endoscopy. 2012; 44: 25Crossref Scopus (1) Google Scholar and European Society of Gastrointestinal Endoscopy15Hassan C. Quintero E. Dumonceau J.-M. et al.Post-polypectomy colonoscopy surveillance: European Society of Gastrointestinal Endoscopy (ESGE) Guideline.Endoscopy. 2013; 45: 842-851Crossref PubMed Scopus (417) Google Scholar guidelines highlight areas of controversy (Table 1). All guidelines emphasize high-quality colonoscopy examinations to affect natural history (ie, prevent CRC and CRC-related death) and to risk stratify patients accurately for subsequent surveillance. Frequent colonoscopy is not viewed as an acceptable alternative to a high-quality examination.Table 1Contrasting Postpolypectomy Surveillance Recommendations After Index Colonoscopy in Three Major GuidelinesMost advanced findings at baseline colonoscopyaUS Multisociety Task Force guidelines define low-risk adenomas as 1 or 2 adenomas <10 mm, and high-risk adenomas as tubular adenoma ≥10 mm, ≥3 adenomas, adenoma with villous histology, or high-grade dysplasia; they recommend that serrated polyps <10 mm without dysplasia can be managed like low-risk adenomas, and sessile serrated polyps ≥10 mm or with dysplasia should be managed like high-risk adenomas.US Multisociety Task Force guidelines13Lieberman D.A. Rex D.K. Winawer S.J. 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: 844-857Abstract Full Text Full Text PDF PubMed Scopus (1425) Google ScholarEuropean guidelinesbEuropean guidelines define low-risk patients as those with 1 or 2 adenomas <10 mm (optional additional criteria of tubular and low-grade neoplasia), intermediate-risk patients as those with 3-4 adenomas <10 mm or at least one 10–19 mm (optional additional criteria of villous or high-grade neoplasia), and high-risk patients as those with ≥5 adenomas <10 mm, or at least one ≥20 mm.14Atkin W.S. Valori R. Kuipers E.J. et al.European guidelines for quality assurance in colorectal cancer screening and diagnosis. First edition–colonoscopic surveillance following adenoma removal.Endoscopy. 2012; 44: 25Crossref Scopus (1) Google ScholarEuropean Society of Gastrointestinal Endoscopy guidelinescEuropean Society of Gastrointestinal Endoscopy guidelines define a low-risk group with 1–2 tubular adenomas <10 mm with low-grade dysplasia and/or serrated polyps <10 mm and no dysplasia, and a high-risk group with adenoma with villous histology or high-grade dysplasia or ≥10 mm in size, or ≥3 adenomas and/or serrated polyps ≥10 mm or with dysplasia.15Hassan C. Quintero E. Dumonceau J.-M. et al.Post-polypectomy colonoscopy surveillance: European Society of Gastrointestinal Endoscopy (ESGE) Guideline.Endoscopy. 2013; 45: 842-851Crossref PubMed Scopus (417) Google Scholar1 or 2 small (<10 mm) tubular adenomasSurveillance in 5-10 yearsReturn to routine screening (for 1 or 2 adenomas <10 mm, interval not specified)Return to national screening program in 10 years; if no program available, then repeat colonoscopy in 10 years3-10 tubular adenomasSurveillance in 3 yearsSurveillance in 3 years (for 3-4 adenomas <10 mm)Surveillance in 3 years≥1 tubular adenoma ≥10 mmSurveillance in 3 yearsSurveillance in 3 years (for ≥1 adenoma 10-19 mm)Surveillance in 3 years≥1 villous adenomaSurveillance in 3 yearsOptional additional criterion for surveillance in 3 yearsSurveillance in 3 years≥1 adenoma with high-grade dysplasiaSurveillance in 3 yearsOptional additional criterion for surveillance in 3 yearsSurveillance in 3 years≥5 adenomas <10 mm, or ≥1 adenoma ≥20 mm (European guidelines “high-risk” group)No specific recommendationClearing colonoscopy in 1 yearNo specific recommendationSessile serrated polyps <10 mm with no dysplasiaSurveillance in 5 years“Serrated adenomas (traditional serrated adenomas and mixed polyps with at least one adenomatous component) should be dealt with like any other adenoma”Return to national screening program in 10 years; if no program available, then repeat colonoscopy in 10 yearsSessile serrated polyps ≥10 mm, or with dysplasia, or traditional serrated adenomaSurveillance in 3 yearsSurveillance in 3 yearsa US Multisociety Task Force guidelines define low-risk adenomas as 1 or 2 adenomas <10 mm, and high-risk adenomas as tubular adenoma ≥10 mm, ≥3 adenomas, adenoma with villous histology, or high-grade dysplasia; they recommend that serrated polyps <10 mm without dysplasia can be managed like low-risk adenomas, and sessile serrated polyps ≥10 mm or with dysplasia should be managed like high-risk adenomas.b European guidelines define low-risk patients as those with 1 or 2 adenomas <10 mm (optional additional criteria of tubular and low-grade neoplasia), intermediate-risk patients as those with 3-4 adenomas <10 mm or at least one 10–19 mm (optional additional criteria of villous or high-grade neoplasia), and high-risk patients as those with ≥5 adenomas <10 mm, or at least one ≥20 mm.c European Society of Gastrointestinal Endoscopy guidelines define a low-risk group with 1–2 tubular adenomas <10 mm with low-grade dysplasia and/or serrated polyps <10 mm and no dysplasia, and a high-risk group with adenoma with villous histology or high-grade dysplasia or ≥10 mm in size, or ≥3 adenomas and/or serrated polyps ≥10 mm or with dysplasia. Open table in a new tab The USMSTF guidelines are organized around the concept of low-risk versus high-risk adenomas, with extrapolation to serrated lesions.13Lieberman D.A. Rex D.K. Winawer S.J. 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: 844-857Abstract Full Text Full Text PDF PubMed Scopus (1425) Google Scholar Large (≥10 mm) serrated lesions are managed as if they were advanced adenomas; small and diminutive serrated lesions are managed as nonadvanced adenomas. Three or more nonadvanced adenomas are managed as advanced adenomas. The European guidelines14Atkin W.S. Valori R. Kuipers E.J. et al.European guidelines for quality assurance in colorectal cancer screening and diagnosis. First edition–colonoscopic surveillance following adenoma removal.Endoscopy. 2012; 44: 25Crossref Scopus (1) Google Scholar propose three patient classifications (low, intermediate and high risk). The “intermediate”-risk group in these guidelines includes persons categorized as “high-risk” adenoma patients in the United States by having 3-4 nonadvanced adenomas. The high-risk group in the European guidelines (≥5 adenomas or polyps ≥20 mm) is best viewed as a very high-risk group from a US perspective. The European Society of Gastrointestinal Endoscopy guidelines dichotomize patients into a low- versus a high-risk group15Hassan C. Quintero E. Dumonceau J.-M. et al.Post-polypectomy colonoscopy surveillance: European Society of Gastrointestinal Endoscopy (ESGE) Guideline.Endoscopy. 2013; 45: 842-851Crossref PubMed Scopus (417) Google Scholar (Table 1). Although each guideline is informed by a literature review examining the risk of metachronous neoplasia based on index colonoscopy findings, the paucity of controlled surveillance studies is an impediment to a fully evidence-based guideline. The differences between guidelines point to areas of uncertainty:•Is surveillance warranted for 1 or 2 nonadvanced adenomas measuring <10 mm? If yes, should this be at 5 years or at 10 years? Should such patients continue with endoscopic testing or can they return to noncolonoscopy (eg, stool-based) screening?•Should a clearing colonoscopy be done at 1 year for a high-risk group with ≥5 adenomas or 1 “very large” (≥20 mm) adenoma or serrated lesion?•Does villous histology or high-grade dysplasia in adenomas <10 mm matter?•What should the surveillance recommendations be after removal of serrated lesions?•How do we integrate baseline screening and initial surveillance findings to decide in whom and when to perform a second or subsequent surveillance? In contemplating future research efforts to clarify the benefit of surveillance, prioritization of specific research questions can be informed by considering the clinical burden, the potential clinical impact of defining optimal practice, and the potential impact on resource demand (Table 2).Table 2Major Areas of Uncertainty in Surveillance Practice and Potential Impact on Clinical Outcomes and Resource DemandPatient subgroupArea of uncertaintyRisk of metachronous advanced lesion or colorectal cancer incidence and mortality in patients subgroupSize of patient subgroup relative to population of all surveillance candidates in the United StatesPotential impact of optimal surveillance on colorectal cancer incidence and mortality in patient subgroupPotential impact of optimal surveillance on colorectal cancer incidence and mortality in population at largePotential impact of surveillance practices on resource demand in population at large1 or 2 small (<10 mm) tubular adenomas at screeningSurveillance? If yes, 5 vs 10 year interval?LowLargeLowLowHigh3-4 diminutive (≤5 mm) tubular adenomas at screeningSurveillance at 3 years?Low to medium?*Growing with improved lesion detection ratesLow to medium?*LowLow to mediumMultiple (eg, ≥5) adenomas or very large (eg, ≥20 mm) adenoma at screening“Clearing colonoscopy” at 1 year?High?Very smallHigh?LowLowTubulovillous or villous adenomas, or high-grade dysplasia <10 mm at screeningSurveillance at 3 years (manage as advanced adenoma)?LowSmallLowLowLow1 or 2 small (<10 mm) serrated lesions at screeningSurveillance? If yes, 5- vs 10-year interval?LowMediumLowLowMediumAdvanced adenoma at screening followed by negative first surveillance examinationSurveillance interval beyond first surveillance examination?MediumSmallHigh?LowLowNOTE. A question mark (?) after a risk or impact estimate implies uncertainly. The addition of an asterisk (*) implies substantial uncertainty. Open table in a new tab NOTE. A question mark (?) after a risk or impact estimate implies uncertainly. The addition of an asterisk (*) implies substantial uncertainty. In the United States, 1 or 2 small, nonadvanced adenomas are the most common neoplastic finding at screening colonoscopy.16Imperiale T.F. Ransohoff D.F. Itzkowitz S.H. et al.Multitarget stool DNA testing for colorectal-cancer screening.N Engl J Med. 2014; 370: 1287-1297Crossref PubMed Scopus (1029) Google Scholar, 17Church T.R. Wandell M. Lofton-Day C. et al.Prospective evaluation of methylated SEPT9 in for detection of asymptomatic colorectal cancer.Gut. 2014; PubMed Scopus Google Scholar In a trial with T.F. Ransohoff D.F. Itzkowitz S.H. et al.Multitarget stool DNA testing for colorectal-cancer screening.N Engl J Med. 2014; 370: 1287-1297Crossref PubMed Scopus (1029) Google Scholar in which all subjects nonadvanced adenomas and advanced adenomas. fecal occult blood testing or fecal immunochemical testing as a to subjects for colonoscopy the of advanced neoplasia. In a evaluation from of colonoscopy after fecal immunochemical of subjects advanced or adenomas and 1 or 2 nonadvanced M. Senore C. Turrin A. et al.Appropriateness of endoscopic surveillance recommendations in organised colorectal cancer screening programmes based on the faecal immunochemical test.Gut. 2015; (21:2015–310139)Crossref Scopus (187) Google Scholar In the United States, 1 or 2 small nonadvanced adenomas are the most prevalent neoplastic finding at and versus more surveillance can a impact on resource demand (Table optimal surveillance practices in subjects with 1 or 2 small nonadvanced adenomas is the The question is whether colonoscopy at year 5 is that whether can removal CRC incidence and mortality between years 5 and or from to adenomas removal at year 10 more risk be at year 5. All guidelines recommend surveillance at 3 years for persons with ≥3 tubular adenomas, but the European guidelines recommend surveillance at 1 year for persons with ≥5 adenomas (Table 1). persons with 3 diminutive adenomas benefit from surveillance at 3 years is The on adenoma detection will the of persons in whom diminutive adenomas are detected, and will be categorized as increase in subjects more surveillance will a substantial demand on the of the benefit of surveillance in individuals in this (Table All guidelines recommend surveillance at 3 years after removal of ≥1 advanced adenomas based on (≥10 but in the European villous and the of high-grade dysplasia in adenomas <10 mm are and finding an adenoma ≥20 mm a surveillance examination at 1 year (Table 1). that to subjects with 1 or 2 adenomas <10 mm with a villous or high-grade dysplasia at 3 years, or return to routine screening at 10 years. advanced histology is in about of small S. et of individuals with low-risk colorectal adenomas clinical a 2015; Scholar the impact of alternative surveillance on CRC or on resource demand is to be (Table All guidelines subsequent testing after removal of an advanced adenoma at screening if the next examination not advanced neoplasia. that advanced adenomas are a risk for Pinsky et colorectal cancer risk surveillance the 2010; Full Text Full Text PDF PubMed Scopus Google Scholar and as repeat surveillance examinations 5 years be D.A. Rex D.K. Winawer S.J. 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: 844-857Abstract Full Text Full Text PDF PubMed Scopus (1425) Google Scholar in the of an examination or an examination with nonadvanced neoplasia (Table The European guidelines a colonoscopy at 1 year for persons with a large number of lesions (≥5 or ≥1 “very large” lesion (≥20 to the The rationale for early surveillance is to lesions were not missed of the potential by to other The impact of a clearing colonoscopy at 1 year versus surveillance at 3 years on interval cancer risk is this is a small the impact on CRC at the population or on resource demand is to be (Table Serrated lesions were in the early years of CRC are now as CRC is an D.K. D.J. et lesions of the review and recommendations from an of 2012; PubMed Scopus Google Scholar lesions are often in the can be and to and are often resected A. et during of the adenoma 2013; Full Text Full Text PDF PubMed Scopus Google Scholar of interval CRCs the with serrated R. et colorectal-cancer incidence and mortality after Engl J Med. 2013; PubMed Scopus Google Scholar endoscopists, is in detection of serrated C.J. Hewett D.G. Norton D.L. et al.Prevalence and variable detection of proximal colon serrated polyps during screening colonoscopy.Clin Gastroenterol Hepatol. 2011; 9: 42-46Abstract Full Text Full Text PDF PubMed Scopus (341) Google Scholar is that surveillance for patients with high-risk serrated lesions could yield substantial serrated are surveillance for these which to be risk for metachronous CRC, could a substantial demand on if the of these lesions as their detection (Table There is in what to recommend for second and subsequent surveillance. on the yield of second surveillance examinations are P.F. R.E. Weissfeld J.L. et al.The yield of surveillance colonoscopy by adenoma history and to Gastroenterol Hepatol. Full Text Full Text PDF PubMed Scopus Google Scholar, Pinsky P.F. et al.Utilization and yield of surveillance colonoscopy in the study of the Gastroenterol Hepatol. Full Text Full Text PDF PubMed Scopus Google Scholar, D.J. et the of a baseline and a surveillance colonoscopy to adenomas with high-risk Med. PubMed Scopus Google Scholar in surveillance in whom the of subsequent neoplasia or 1 or 2 are at risk of metachronous studies do that subjects with an advanced adenoma are at risk for Pinsky et colorectal cancer risk surveillance the 2010; Full Text Full Text PDF PubMed Scopus Google Scholar Although the of repeated surveillance examinations be substantial for persons in this the impact on demand for is to be (Table The of or 2 nonadvanced is a patient with a tubular adenoma as as a patient with to sessile adenomas, on the of an advanced Should these 2 patients be managed one a diminutive adenoma and the other 2 more nonadvanced studies show that to polyps can to advanced lesions within a et of of small colorectal polyps with a study of natural 2013; Full Text Full Text PDF PubMed Scopus Google Scholar In a observational natural history 3 years, of polyps mm as defined by a of C.J. et of small mm) polyps after a surveillance of with compared with of 2015; Scholar The risk of CRC be for a patient to adenomas versus a patient a if these lesions were not that is not the The question is whether these risk is to a The risk of metachronous neoplasia be for the patient with to adenomas, but is the to a surveillance data from trials that risk differences are to be S. et of individuals with low-risk colorectal adenomas clinical a 2015; Scholar the of natural A. R.E. et a natural to to on colonoscopy quality 2012; Full Text Full Text PDF PubMed Scopus Google Scholar, C. et colonoscopy quality natural of 2015; PubMed Scopus (50) Google Scholar of of and pathology are are to studies of community-based surveillance such as from the large and from large with longstanding will a of to define the practice of surveillance more the will on the available, and will not be to or are diagnosed with CRC of the in the studies will In the European POlyp Surveillance trial is The subjects with 1 or 2 nonadvanced adenomas will be CRC incidence between years 5 and The trial is as a that any differences in CRC incidence between the 2 will be to be In the United States, is the patients and that is Colonoscopy is often practice is for and for There is is for often they are and what and is are the of return for are to There is to be more and and based on quality are patients to their more are and a population perspective. could affect surveillance colonoscopy will be In the United States, efforts are underway to on a surveillance colonoscopy study to that in years the of the randomized trial of S.J. Zauber A.G. et of surveillance after removal of diagnosed adenomatous The Engl J Med. PubMed Scopus Google Scholar which surveillance colonoscopy from to 3 years the incidence of advanced adenomas in subjects at 1 and 3 years versus those at 3 years. to surveillance practice beyond 3 years is and to the current of clinical Postpolypectomy surveillance is an As CRC screening of the population and the on adenoma detection the of surveillance will and the demand on will The benefit of surveillance is more the benefit of research should at at surveillance recommendations that or not or but just