Postpolypectomy surveillance has become a major indication for colonoscopy as a result of increased use of screening colonoscopy in Korea. In this report, a careful analytic approach was used to address all available evidences to delineate the predictors for advanced neoplasia at surveillance colonoscopy and we elucidated the high risk findings of the index colonoscopy as follows: 3 or more adenomas, any adenoma larger than 10 mm, any tubulovillous or villous adenoma, any adenoma with high-grade dysplasia, and any serrated polyps larger than 10 mm. Surveillance colonoscopy should be performed five years after the index colonoscopy for those without any high-risk findings and three years after the index colonoscopy for those with one or more high risk findings. However, the surveillance interval can be shortened considering the quality of the index colonoscopy, the completeness of polypectomy, the patient's general condition, and family and medical history.
The detection and removal of colorectal polyps using colonoscopy is the most effective method of preventing colorectal cancer (CRC) and CRC-related deaths.
To this end, postpolypectomy surveillance guidelines have been established and revised in several Western countries.
The present guideline is designed as a patient care reference that will support physicians who are responsible for patients with colorectal polyps and for conducting colonoscopies in clinical practice. In the present report, a careful analytic approach was designed to address all of the available evidence in the literature that delineates predictors of advanced neoplasms, both cancers and advanced adenomas, with the aim of risk stratifying patients based on their index colonoscopy. However, the available Korean studies were not sufficient; therefore, expert opinions were collected using an internet survey and a Delphi meeting to represent the characteristics of the Korean population and the medical environment in Korea.
Asymptomatic persons aged 50 years or older who are concerned about the possible presence of CRC are advised to receive CRC screening colonoscopies. Because the risk of future CRC is increased in patients who have undergone polyp removal, it is recommended that these patients participate in a periodic surveillance program.
Most of the systematically identified studies used as evidence in the present report were performed in Western countries, and the number of studies performed in Korea was limited. Therefore, the taskforce undertook web-based surveys to ascertain current Korean clinical practices and a Delphi meeting with clinical experts to explore the level of agreement on the initial practical guideline proposal. In addition, because most of the studies used evidence from observational studies rather than randomized controlled trials, the quality of evidence for this guideline was generally graded as low.
To develop this guideline, a multi-society taskforce consisting of experts recommended by the KSG, the KSGE, the Korean Association for the Study of the Intestinal Diseases and the Korean Society of Abdominal Radiology was established in June 2010. There were no conflicts of interest for any of the participating members.
The developed guideline will be co-published in the journals of the KSG, the KSGE, the Korean Association for the Study of Intestinal Disease (KASID) and the Journal of the Korean Society of Radiology. The guideline will also be published th-rough the websites of the relevant societies and in major medical newspapers. Additionally, the contents will be widely distributed through a summary guidebook to training hospitals.
After a certain amount of time has passed after the distribution and implementation of the guidelines, adherence to the guideline in clinical practice will be assessed. Furthermore, the contents will be periodically revised to reflect the latest clinical knowledge.
The medical terms related to colonoscopic surveillance in this guideline were chosen to be consistent with the terms used in previous studies.
1) Postpolypectomy surveillance: Periodic examination of the colon to detect synchronous or metachronous neoplasia after polypectomy. This term does not include the use of colonoscopy or other procedures to monitor for polyp or cancer recurrence following a diagnosis of CRC.
2) Advanced adenoma: An adenoma of 10 mm or larger, an adenoma with high-grade dysplasia, or an adenoma containing 25% or more villous components.
3) Advanced neoplasia: An advanced adenoma or invasive cancer.
4) Index colonoscopy: The colonoscopy conducted most recently prior to the surveillance colonoscopy. The index colonoscopy should be performed according to the quality guideline of CRC screening recommended by the Ministry of Health and Walfare.
5) Index adenoma: The largest adenoma found in an index colonoscopy. If all of the adenomas are smaller than 10 mm, the index adenoma refers to any adenoma that contains high-grade dysplasia or 25% or more villous components.
Although the incidence of CRC and CRC-related mortality are ideal outcome measures for evaluating the effectiveness of postpolypectomy surveillance, they are not practical to use because they require lengthy follow-up. Thus, advanced neoplasia, which includes both advanced adenoma and invasive cancer, has commonly been adopted as a surrogate biological marker for CRC.
The following key questions were selected for constructing postpolypectomy colonoscopic surveillance guidelines. 1) What are the risk factors for subsequent advanced neoplasia that must be considered when determining the colonoscopy surveillance interval? 2) Based on these risk factors, how can patients with a high risk of subsequent advanced neoplasia be identified? 3) What is the optimal colonoscopy surveillance interval in patients without risk factors for subsequent advanced neoplasia? 4) What is the optimal colonoscopy surveillance interval in patients with a high risk of subsequent advanced neoplasia?
The literature review process began with a systematic MEDLINE, Cochrane Library and National Guideline Clearinghouse search for guidelines addressing surveillance colonoscopy after endoscopic resection of colorectal polyps that were published between 2000 and 2010. Both the postpolypectomy colonoscopic surveillance guidelines of the US Multi-Society Task Force on Colorectal Cancer and the American Cancer Society (USMSTF-ACS)
For the systematic literature review, electronic databases, including MEDLINE and the Cochrane Library, were searched from January 2000 and September 2010 to identify potentially relevant English-language articles. The keywords used in the English searches were "colonoscopy" AND "colon OR colonic OR colorecta" AND "polyp OR neoplasm OR neoplasia." Studies that were published in Korean were identified using the Korean Studies Information Service System (
Among the reviewed studies, 17 presented the adjusted odds ratio (OR), adjusted relative risk (RR) or hazard ratio (HR) and 95% confidence intervals (95% CI) for one or more of the risk factors for subsequent advanced neoplasia during postpolypectomy colonoscopic surveillance and were included in a meta-analysis (
Recommendations are presented based on a systematic review of the selected literature and meta-analyses. The quality of evidence, indicating the degree to which each recommendation has scientific evidence, and the strength of the recommendations were determined following the methodology proposed by the Grading of Recommendations Assessment, Development and Evaluation Working Group (
The quality of evidence was assessed to be "high" when evidence consisted of randomized controlled trials and "low" in cases where evidence included observational studies. However, in cases where studies used as evidence had limitations in the study design or execution, inconsistent results, indirect evidence, imprecise results or publication bias, the quality of evidence was adjusted downward. In cases of observational studies where large effects were observed, where reported effects might have been reduced due to confounding variables or where dose-response gradients existed, the quality of evidence was adjusted upward. The strength of each recommendation was assessed as "strong" or "weak" by considering the balance of desirable and undesirable consequences, the quality of the evidence, the confidence in the values and the references and the effective allocation of medical expenses and resources. That is, in cases where it was judged that following a specific recommendation would lead to significant health benefits or losses for most patients, the strength of the recommendation was classified as "strong." The strength of the recommendation was classified as "weak" in cases where it was judged that following the recommendation would lead to important benefits or loss in terms of the quality of the health of patients but where differences existed among patients, thus leading to the need to consider individual environments, preferences and values.
The colonoscopy surveillance intervals recommended in this postpolypectomy colonoscopic surveillance guideline were determined according to an evaluation of the risk factors for subsequent advanced neoplasia, including the characteristics of the polyps found in the index colonoscopy and other patient characteristics:
Patients with three or more adenomas have an increased risk of subsequent advanced neoplasia.
Quality of evidence: high Level of agreement: completely agree (74%), generally agree (24%), partially agree (3%), generally disagree (0%), and totally disagree (0%)
Nine observational studies, including one pooled analysis
Similar to the results of the meta-analysis, the patients in a Korean prospective cohort study with ≥3 adenomas showed an increased risk of subsequent advanced neoplasia, with an adjusted HR of 3.06 (95% CI, 1.51 to 6.57), compared with the patients diagnosed with ≥2 adenomas.
By contrast, several studies have reported that polyp miss rates significantly increase as the number of polyps found in the index colonoscopy increases.
In addition, previously published guidelines have recommended shortening the colonoscopy surveillance interval in patients with multiple polyps. The British Society of Gastroenterology/Association of Coloproctology for Great Britain and Ireland recommends performing a surveillance colonoscopy at 1 year in patients with ≥5 adenomas or ≥3 adenomas including at least one that is ≥1 cm,
Patients with an adenoma that is 1 cm or larger have an increased risk of advanced neoplasia.
Quality of evidence: moderate Level of agreement: completely agree (59%), generally agree (35%), partially agree (5%), generally disagree (0%), and totally disagree (0%)
Eight observational studies, including one pooled analysis
Similar results have been found in a Korean prospective cohort study in which the HR of the subsequent advanced neoplasia in the patients with ≥10 mm adenomas was 3.02 (95% CI, 1.80 to 5.06).
Large adenomas have an increased probability of containing areas with advanced histology, including villous or high-grade dysplasia and carcinoma. Previous studies have reported that the likelihood of a ≥20 mm adenoma containing an area of carcinoma may be as high as 32%.
Patients with tubulovillous or villous adenomas have an increased risk of advanced neoplasia.
Quality of evidence: low Level of agreement: completely agree (26%), generally agree (53%), partially agree (16%), generally disagree (5%), and totally disagree (0%)
Seven observational studies, including one pooled analysis
In a Korean prospective cohort studies, by contrast, the patients with villous or tubulovillous adenomas did not have an increased risk of subsequent advanced adenoma (HR, 1.48; 95% CI, 0.74 to 2.95).
Patients with high-grade dysplasia adenomas have an increased risk of subsequent advanced neoplasia.
Quality of evidence: low Level of agreement: completely agree (34%), generally agree (55%), partially agree (11%), generally disagree (0%), and totally disagree (0%)
After Atkin et al.
By contrast, a pooled analysis by Martinez et al.
Patients with serrated polyps 10 mm in size or larger have an increased risk of subsequent advanced neoplasia.
Quality of evidence: very low Level of agreement: completely agree (3%), generally agree (61%), partially agree (34%), generally disagree (3%), and totally disagree (0%)
Serrated polyps are a heterogeneous group of lesions characterized by the glandular serration (that is, a "saw-toothed" architecture of the crypt epithelium).
In the systematic literature review, electronic databases (MEDLINE and the Cochrane Library) entries from January 2000 to September 2010 were searched to identify potentially relevant articles using "serrated" AND "polyp OR adenoma" as keywords. A total of 52 studies were found. Three observational studies assessed the risk of CRC in patients with serrated polyps ≥10 mm in size by assessing the coexistence of advanced neoplasia (
A previous pooled analysis of two randomized chemoprevention trials has indicated that the incidence of overall colo-rectal adenoma was not increased in surveillance colonoscopies performed 3 years after the removal of hyperplastic polyps.
The association between adenoma distribution and the risk of subsequent advanced neoplasia has been recently evaluated in a pooled analysis
Recent studies have suggested that right-sided colon cancer can develop through the serrated pathway.
The association between the risk of subsequent advanced neoplasia and patient age has been evaluated in one pooled analysis
Several studies have assessed whether patient sex was associated with the risk of subsequent advanced neoplasia (
Although a familial history of CRC was reported to have a positive association with the risk of subsequent advanced neoplasia in some studies,
A limited number of studies have assessed the effects of smoking and obesity on the risk of subsequent advanced neoplasia upon colonoscopic surveillance. In a pooled analysis by Martinez et al.
It is well known that the risk of subsequent colorectal adenoma and advanced neoplasia is increased in patients with polyps compared to patients without polyps.
Based on the results of the systematic literature reviews and a meta-analysis, patients with any of the following index colonoscopy findings had an increased risk of subsequent advanced neoplasia: 1) 3 or more adenomas, 2) any adenoma larger than 10 mm, 3) any tubulovillous or villous adenoma, 4) any adenoma with high-grade dysplasia, and 5) any serrated polyps larger than 10 mm. Therefore, patients who exhibit any of these findings should be classified as being at high risk for subsequent advanced neoplasia for the purposes of postpolypectomy surveillance (
In patients without a high-risk finding at the index colonoscopy, surveillance colonoscopy should be performed five years after a high-quality index colonoscopy is administered by a qualified endoscopist. However, the surveillance interval can be shortened if the quality of the index colonoscopy was not high or if a high-risk finding was observed in a colonoscopy prior to the index colonoscopy.
Quality of evidence: low Level of recommendation: weak Level of agreement: completely agree (23%), generally agree (41%), partially agree (31%), generally disagree (5%), and totally disagree (0%)
In the 1990s and earlier, before there was sufficient evidence to recommend an appropriate postpolypectomy surveillance interval, surveillance colonoscopy was generally conducted on a yearly basis. The National Polyp Study was the first randomized controlled trial to address the question of an adequate postpolypectomy surveillance interval. In this study, 1,418 patients who had undergone removal of one or more adenomas were randomized into a two-examination group (with a surveillance colonoscopy at 1 year and 3 years) and a one-examination group (with a surveillance colonoscopy at 3 years). The percentage of patients with adenomas with advanced pathological features was the same in both groups (3.3%). Therefore, an interval of 3 years between colonoscopic adenoma removal and a surveillance colonoscopy to detect advanced neoplasia was suggested.
In a large rigid sigmoidoscopy cohort study published in 1992, the patients with ≤10 mm tubular adenomas did not show an increased risk of subsequent CRC after polypectomy compared to the general population.
Lieberman et al.
Currently, the intervals suggested for postpolypectomy surveillance colonoscopy are based on the findings from the index colonoscopy, i.e., the most recent high-quality colonoscopy. Recently, Robertson et al.
In patients with a high risk of subsequent advanced neoplasia, surveillance colonoscopy should be performed three years after a high-quality index colonoscopy is administered by a qualified endoscopist. However, the surveillance interval can be shortened if the quality of the index colonoscopy was low or based on the index colonoscopy findings, the completeness of polyp removal, patient conditions, family history and medical history.
Quality of evidence: low Strength of a recommendation: weak Level of agreement: completely agree (21%), generally agree (44%), partially agree (23%), generally disagree (10%), and totally disagree (3%)
Most of the high-quality studies that have evaluated the risk factors for subsequent advanced neoplasia are observational studies conducted on participants in polyp prevention trials. Because these studies were conducted after the National Polyp Study and the Funen adenoma follow-up study, most of the polyp prevention trials have included a three- or four-year surveillance interval.
Furthermore, it has not yet been determined whether the risk of subsequent advanced neoplasia increases in patients with two or more overlapping high-risk findings. In a large-scale rigid sigmoidoscopy study by Atkin et al.,
Because patients with colorectal adenomas are at increased risk for subsequent colorectal neoplasia compared to patients with no polyps, periodic postpolypectomy colonoscopic surveillance is necessary.
Based on the literature review and evidence, it is recommended that colonoscopic surveillance in Korea be performed 3 years after polypectomy in those patients with high-risk findings and 5 years after in those patients without high-risk findings.
However, several factors should be considered before determining the surveillance colonoscopy interval (
Previous guidelines have suggested short surveillance intervals of 1 to 3 years for patients with 10 or more adenomas. However, these recommendations have not been based on sufficient evidence.
This is the first postpolypectomy surveillance guideline published for Korea. Because the Korean data on postpolypectomy surveillance were quite limited, many of these recommendations were made based on evidence from Western countries in which the health care environments are different from that of Korea. In particular, colonoscopy fees are lower in Korea than in Western countries; therefore, further cost-effectiveness analysis should be conducted using the results of colorectal polyp studies performed with Korean populations. Finally, it is emphasized that this guideline cannot address all clinical situations and thus cannot supersede clinical judgments that consider the specific characteristics of individual patients.
Patients with three or more adenomas have an increased risk of subsequent advanced neoplasia. Patients with an adenoma that is 1 cm or larger have an increased risk of advanced neoplasia. In cases where tubulovillous or villous adenomas have been found in the index colonoscopy, the risk of detecting advanced neoplasia in a surveillance colonoscopy is increased compared with the risk in patients with non-villous tubular adenomas. Patients with tubulovillous or villous adenomas have an increased risk of advanced neoplasia. Patients with high-grade dysplasia adenomas have an increased risk of subsequent advanced neoplasia. Patients with serrated polyps 10 mm in size or larger have an increased risk of subsequent advanced neoplasia. Patients should be considered at high risk for subsequent advanced neoplasia at surveillance colonoscopy when one or more of the following conditions have been detected at index colonoscopy: 1) 3 or more adenomas, 2) any adenoma larger than 10 mm, 3) any tubulovillous or villous adenoma, 4) any adenoma with high-grade dysplasia, and 5) any serrated polyps larger than 10 mm. In patients without a high-risk finding at the index colonoscopy, surveillance colonoscopy should be performed five years after a high-quality index colonoscopy is administered by a qualified endoscopist. However, the surveillance interval can be shortened if the quality of the index colonoscopy was not high or if a high-risk finding was observed in a colonoscopy prior to the index colonoscopy. In patients with a high risk of subsequent advanced neoplasia, surveillance colonoscopy should be performed three years after a high-quality index colonoscopy is administered by a qualified endoscopist. However, the surveillance interval can be shortened if the quality of the index colonoscopy was low or based on the index colonoscopy findings, the completeness of polyp removal, patient conditions, family history and medical history.
We extend profound thanks to Professor Chae, Hiun Suk (The Catholic University of Korea College of Medicine), Professor Han, Dong Soo (Hanyang University Guri Hospital), and Professor Jeen, Yoon Tae (Korea University College of Medicine) who gave unsparing advice regarding the development of these guidelines for postpolypectomy surveillance.
We also give great thanks to the Korean Association of Internal Medicine and Korean Physicians Association for their agreement with final version of these guidelines.
This study was initiated with the support of the Korean Society of Gastroenterology, the Korean Society of Gastrointestinal Endoscopy, and the Korean Association for the Study of Intestinal Disease. This study was supported by a grant for the Korean Health Technology R&D Project with the Ministry for Health and Welfare of the Republic of Korea (A102065-23).
The authors have no financial conflicts of interest.
These guidelines are being co-published in the Korean Journal of Gastroenterology, the Intestinal Research, and the Clinical Endoscopy for the facilitated distribution.
Flow chart outlining search process used to identify articles for inclusion in systematic review and meta-analysis.
Forest plot for the number of colorectal adenomas as a risk factor for advanced neoplasia. CI, confidence interval.
Forest plot for the size of colorectal adenomas as a risk factor for advanced neoplasia. CI, confidence interval.
Forest plot for villous/tubulovillous adenomas as a risk factor for advanced neoplasia. CI, confidence interval, TA, tubular adenoma.
Forest plot for adenomas with high grade dysplasia as a risk factor for advanced neoplasia. CI, confidence interval.
Forest plot of the large (≥10 mm) serrated polyps at index colonoscopy as a risk factor for advanced neoplasia. CI, confidence interval.
Forest plot for the location of index polyps as a risk factor for advanced neoplasia. CI, confidence interval.
Forest plot for the gender as a risk factor for advanced neoplasia. CI, confidence interval.
Forest plot for the family history of colorectal cancers as a risk factor for advanced neoplasia. CI, confidence interval.
Quality of Evidence and Strength of a Recommendation
Patients with a High Risk of Subsequent Advanced Neoplasia at Postpolypectomy Surveillance Colonoscopy
Prerequisite to Determine the Surveillance Colonoscopy Interval Based on the Guideline