GASTROENTEROLOGY 2006;130:1872–1885
Guidelines for Colonoscopy Surveillance After Polypectomy:
A Consensus Update by the US Multi-Society Task Force on
Colorectal Cancer and the American Cancer Society
SIDNEY J. WINAWER,* ANN G. ZAUBER,* ROBERT H. FLETCHER,‡ JONATHON S. STILLMAN,*
MICHAEL J. O’BRIEN,§ BERNARD LEVIN,储 ROBERT A. SMITH,¶ DAVID A. LIEBERMAN,#
RANDALL W. BURT,** THEODORE R. LEVIN,‡‡ JOHN H. BOND,§§ DURADO BROOKS,¶
TIM BYERS,¶¶ NEIL HYMAN,储 储 LYNNE KIRK,## ALAN THORSON,*** CLIFFORD SIMMANG,##
DAVID JOHNSON,††† and DOUGLAS K. REX‡‡‡
*Memorial Sloan-Kettering Cancer Center, New York, New York; ‡Harvard Medical School, Boston, Massachusetts; §Boston University School
of Medicine, Boston, Massachusetts; 储University of Texas M.D. Anderson Cancer Center, Houston, Texas; ¶American Cancer Society, Atlanta,
Georgia; #Oregon Health and Science University, Portland, Oregon; **Huntsman Cancer Institute at the University of Utah, Salt Lake City,
Utah; ‡‡Kaiser Permanente Medical Center, Walnut Creek, California; §§University of Minnesota, Minneapolis, Minnesota; ¶¶University of
Colorado, Denver, Colorado; 储 储University of Vermont, Burlington, Vermont; ##University of Texas Southwestern Medical Center, Dallas, Texas;
***Creighton University, Omaha, Nebraska; †††Eastern Virginia School of Medicine, Norfolk, Virginia; and ‡‡‡Indiana University School of
Medicine, Indianapolis, Indiana
Adenomatous polyps are the most common neoplastic
findings discovered in people who undergo colorectal
screening or who have a diagnostic work-up for symptoms. It was common practice in the 1970s for these
patients to have annual follow-up surveillance examinations to detect additional new adenomas and missed
synchronous adenomas. As a result of the National
Polyp Study report in 1993, which showed clearly in a
randomized design that the first postpolypectomy examination could be deferred for 3 years, guidelines published by a gastrointestinal consortium in 1997 recommended that the first follow-up surveillance take place 3
years after polypectomy for most patients. In 2003
these guidelines were updated and colonoscopy was
recommended as the only follow-up examination, stratification at baseline into low risk and higher risk for
subsequent adenomas was suggested. The 1997 and
2003 guidelines dealt with both screening and surveillance. However, it has become increasingly clear that
postpolypectomy surveillance is now a large part of
endoscopic practice, draining resources from screening
and diagnosis. In addition, surveys have shown that a
large proportion of endoscopists are conducting surveillance examinations at shorter intervals than recommended in the guidelines. In the present report, a careful analytic approach was designed to address all
evidence available in the literature to delineate predictors of advanced pathology, both cancer and advanced
adenomas, so that patients can be stratified more definitely at their baseline colonoscopy into those at lower
risk or increased risk for a subsequent advanced neoplasia. People at increased risk have either 3 or more
adenomas, high-grade dysplasia, villous features, or an
adenoma 1 cm or larger in size. It is recommended that
they have a 3-year follow-up colonoscopy. People at
lower risk who have 1 or 2 small (<1 cm) tubular
adenomas with no high-grade dysplasia can have a
follow-up evaluation in 5–10 years, whereas people with
hyperplastic polyps only should have a 10-year follow-up
evaluation, as for average-risk people. There have been
recent studies that have reported a significant number
of missed cancers by colonoscopy. However, high-quality
baseline colonoscopy with excellent patient preparation
and adequate withdrawal time should minimize this and
reduce clinicians concerns. These guidelines were developed jointly by the US Multi-Society Task Force on Colorectal Cancer and the American Cancer Society to provide a broader consensus and thereby increase the use
of the recommendations by endoscopists. The adoption
of these guidelines nationally can have a dramatic impact on shifting available resources from intensive surveillance to screening. It has been shown that the first
screening colonoscopy and polypectomy produces the
greatest effects on reducing the incidence of colorectal
cancer in patients with adenomatous polyps.
Abbreviations used in this paper: CI, confidence interval; FOBT, fecal
occult blood testing; HNPCC, hereditary nonpolyposis colorectal cancer; HR, hazard ratio; OR, odds ratio; RCT, randomized controlled trial;
RR, relative risk; SIR, standardized incidence ratio.
© 2006 by the American Gastroenterological Association Institute
This article is being published jointly in 2006 in CA: A Cancer Journal
for Clinicians (online: May 30, 2006; print: May/June 2006) and Gastroenterology (online: May 2006; print: May 2006) by the American
Cancer Society and the American Gastroenterology Association.
©2006 American Cancer Society, Inc. and American Gastroenterology
Association, Inc. Copying with attribution allowed for any noncommercial
use of the work.
0016-5085/06/$32.00
doi:10.1053/j.gastro.2006.03.012
May 2006
A
denomatous polyps are the most frequent neoplasm found during colorectal screening.1– 4 Removal of these lesions has been shown to reduce the
risk for future colorectal cancer and advanced adenomas.5–12 To minimize the risk for colorectal cancer
further, patients with adenomas usually are placed
into a surveillance program of periodic colonoscopy to
remove missed synchronous and new metachronous
adenomas and cancers.13–16 A large number of patients
with adenomas now are being discovered as a result of
the increased use of colorectal cancer screening, particularly the dramatic increase in screening colonoscopy, and this places a huge burden on medical resources applied to surveillance.17–19 Therefore, there is
a need for increased efficiency of surveillance colonoscopy practices to decrease the cost, risk, and overuse of
resources for unnecessary examinations.
Therefore, the US Multi-Society Task Force on Colorectal Cancer and the American Cancer Society have
issued updated joint guidelines on postpolypectomy surveillance. These guidelines differ from the earlier guidelines in several specific ways (Table 1)13–16: we offer a
consensus statement that strengthens the guidelines; we
specifically examined predictors of advanced adenomas
and incorporated them into the guidelines; and we emphasized the quality of baseline colonoscopy and its
impact on detection of postpolypectomy colorectal cancer.5,20,21 We reviewed recent evidence, particularly as it
pertains to stratifying patients for future risk for advanced adenomas.
Table 1. Differences From Prior Postpolypectomy Guidelines
1. The overall goal of these guidelines is to identify predictors of
subsequent advanced adenomas and cancers to stratify
patients into lower- and higher-risk groups
2. These guidelines focus on the earlier-described risk
stratification to encourage a shift from intense surveillance to
surveillance based on risk; this would free up endoscopic
resources for screening, diagnosis, and appropriate surveillance
3. High-quality baseline colonoscopy is emphasized as critical for
effectively reducing colon cancer risk
4. Completeness of polypectomy at baseline is emphasized,
particularly in the setting of piecemeal removal of large sessile
polyps
5. Follow-up surveillance of hyperplastic polyps is discouraged,
except in the case of hyperplastic polyposis
6. The importance of increasing awareness of hyperplastic
polyposis is discussed
7. The use of FOBT during surveillance is discouraged at present,
but requires further study
8. Follow-up intervals after removal of 1 or 2 small (⬍ 1 cm)
adenomas have been lengthened (5–10 years or average-risk
screening options) and, within this range, left to the clinician’s
judgment and the patient’s preference
9. Evolving technologies such as chromoendoscopy, magnification
endoscopy, and computed tomography colonography (virtual
colonoscopy) are not yet established as surveillance modalities
POSTPOLYPECTOMY SURVEILLANCE
1873
Table 2. Surveillance Recommendations
1. Patients with small rectal hyperplastic polyps should be
considered to have normal colonoscopies, and therefore the
interval before the subsequent colonoscopy should be 10
years; an exception is patients with a hyperplastic polyposis
syndrome; they are at increased risk for adenomas and
colorectal cancer and need to be identified for more intensive
follow-up evaluation
2. Patients with only 1 or 2 small (⬍1 cm) tubular adenomas with
only low-grade dysplasia should have their next follow-up
colonoscopy in 5–10 years; the precise timing within this
interval should be based on other clinical factors (such as prior
colonoscopy findings, family history, and the preferences of the
patient and judgment of the physician)
3. Patients with 3 to 10 adenomas, or any adenoma ⱖ1 cm, or
any adenoma with villous features, or high-grade dysplasia
should have their next follow-up colonoscopy in 3 years
providing that piecemeal removal has not been performed and
the adenoma(s) are removed completely; if the follow-up
colonoscopy is normal or shows only 1 or 2 small tubular
adenomas with low-grade dysplasia, then the interval for the
subsequent examination should be 5 years
4. Patients who have more than 10 adenomas at 1 examination
should be examined at a shorter (⬍3 y) interval, established by
clinical judgment, and the clinician should consider the
possibility of an underlying familial syndrome
5. Patients with sessile adenomas that are removed piecemeal
should be considered for follow-up evaluation at short intervals
(2–6 mo) to verify complete removal; once complete removal
has been established, subsequent surveillance needs to be
individualized based on the endoscopist’s judgment;
completeness of removal should be based on both endoscopic
and pathologic assessments
6. More intensive surveillance is indicated when the family history
may indicate HNPCC
Risk stratification could reduce markedly the intensity of follow-up evaluation in a substantial proportion
of patients, so that colonoscopy resources could be
shifted from surveillance to screening and diagnosis.
Risk stratification also could reduce the small, but
finite, screening colonoscopy complication rate.22 This
set of guidelines is the latest in a series, begun in
1997, updated in 2003, and builds on the concept of
change consistent with new evidence.13–16 It incorporates the American College of Gastroenterology polyp
guidelines from 2000.23 Before the earlier-described
guidelines, physicians had minimal guidance in managing postpolypectomy patients. Our goal is to provide a continuing basis for recommendations to guide
postpolypectomy follow-up evaluation.
These guidelines (Tables 2 and 3) have been endorsed
by the Colorectal Cancer Advisory Committee of the
American Cancer Society and by the governing boards of
the American College of Gastroenterology, the American
Gastroenterological Association, and the American Society for Gastrointestinal Endoscopy.
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WINAWER ET AL
Table 3. Additional Surveillance Considerations
1. The present recommendations assume that colonoscopy is
complete to the cecum and that bowel preparation is adequate;
a repeat examination should be performed if the bowel
preparation is not adequate before planning a long-term
surveillance program
2. There is clear evidence that the quality of examinations is highly
variable; continuous quality improvement process is critical to
the effective application of colonoscopy in colorectal cancer
prevention
3. A repeat examination is warranted if there is a concern that the
polyp was removed incompletely, particularly if it shows highgrade dysplasia
4. Endoscopists should make clear recommendations to primary
care physicians about when the next colonoscopy is indicated
5. Given the evolving nature of guidelines, it is important that
physicians and patients should remain in contact so that
surveillance recommendations reflect changes in guidelines
6. Pending further investigation, performance of FOBT is
discouraged in patients undergoing colonoscopic surveillance
7. Discontinuation of surveillance colonoscopy should be
considered in patients with serious comorbidities with less than
10 years of life expectancy, according to the clinician’s
judgment
8. Surveillance guidelines are intended for asymptomatic people;
new symptoms may need diagnostic work-up
9. The application of evolving technologies such as
chromoendoscopy, magnification endoscopy, narrow band
imaging, and computed tomography colonography are not
established for postpolypectomy surveillance at this time
Methodology and Literature Review
We performed a Medline search of the postpolypectomy literature under the subject headings
“colonoscopy” and “adenoma,” “polypectomy surveillance,” and “adenoma surveillance,” limited to English
language articles from 1990 to 2005. This search identified 35 articles based on inclusion of data pertaining to
baseline colonoscopy characteristics, advanced adenoma
detection during follow-up surveillance, and advanced
adenoma characteristics. Subsequently, we identified 12
additional articles from references of reviewed articles. Of
these 47 articles we considered 13 to be relevant studies
according to the following criteria: (1) colonoscopy studies specifically addressing the relationship between baseline examination findings and the detection of advanced
adenoma or of any adenoma during follow-up colonoscopy; or (2) sigmoidoscopy studies, with large cohorts
and follow-up periods longer than 10 years, specifically
addressing the association between baseline examination
findings and the detection of advanced adenomas during
follow-up evaluation. After the initial review of published data, we added 1 relevant abstract and a newly
published article to the review. These were studies that
were identified by members of the guideline committee
and for which the data were available to the committee.
We excluded studies that included patients with inflam-
GASTROENTEROLOGY Vol. 130, No. 6
matory bowel disease, a prior history of colorectal cancer,
and familial syndromes. Our final review was based on 15
studies that met the inclusion criteria.5,7,12,20,21,24 –35 The
most recent publication for the outcome of interest (adenomas and advanced neoplasia) was used for studies
with more than 1 publication. We gave separate listings
to the St. Mark’s study by Atkin et al7 for the outcomes
for colon cancer and for rectal cancer. Two studies reported only on risk factors for adenomas rather than for
advanced adenomas at surveillance.32,34
The literature review was conducted by 2 independent
authors (S.J.W. and J.S.S.). A third author (A.G.Z.)
created the evidence table that was circulated among
members of the US Multisociety Task Force on Colorectal Cancer and the American Cancer Society’s Colorectal
Cancer Advisory Committee. Recommendations in this
report were based on the review of the evidence and the
discussions at the combined meeting.
The appendix (see supplemental material online at
www.gastrojournal.org) was organized to include the
elements of study design. Ideally the best study design
would fulfill the following criteria:
1. Be a randomized controlled trial (RCT) or an observational cohort study of patients with adenoma(s) at
baseline that were cleared by colonoscopy, after excluding people at high risk (such as familial syndromes).
2. Consider all the candidate risk factors.
3. Have sufficient follow-up time for adenomas to develop, with few drop-outs.
4. Have planned colonoscopic assessment for recurrence
in all patients in the cohort.
5. Have enough outcome events for reasonable statistical
precision and sufficient statistical power to detect
associations between baseline characteristics and adenoma outcomes.
6. Present the analyses that include adjustment for multiple risk factors and consider what the independent
effects are.
The appendix (see supplemental material online at
www.gastrojournal.org) includes classification of the type
of design (RCTs or observational cohort studies), the
number of patients at risk, the follow-up intervals recommended, and the length of time patients were followed-up. We also list the variables considered as risk
factors and the effect of these factors on the incidence of
subsequent adenomas or on advanced neoplasia. The
multivariate estimate of the relative risk was presented
whenever available. The definition of an advanced neoplasia is given for each study and varies considerably by
May 2006
study. Summary comments on each study also are included.
Review of the evidence was confounded by variations in definitions, design of the studies, timing and
multiplicity of surveillance intervals, and quality of
the baseline colonoscopy (see the appendix in supplemental material online at www.gastrojournal.
org). Because of these variations, the review of the
literature cited was descriptive rather than a single
summary value of risk (ie, meta-analysis) for all studies. The literature cited is grouped by type of study
design: (1) RCTs in which the surveillance interval is
set and maintained as much as possible although
eligibility requirements may vary; (2) observational
cohort studies that are primarily registry studies with
more passive recruitment for surveillance. The RCTs
provide stronger evidence for the timing of follow-up
examinations because those who received surveillance
colonoscopy were not a special subset of all enrolled.
As noted earlier, relative risks or odds ratios (ORs)
from multivariate analyses were presented in the appendix (see supplemental material online at www.
gastrojournal.org) whenever available. For 2 studies,7,21 the measure of risk was the standardized incidence ratio (SIR) with adjustment for age and sex
rather than a relative risk. In 1 study,12 the hazard
ratio is given as the measure of the effect. A descriptive graphic presentation was given with point estimates and confidence intervals for the relative risk for
adenomas and advanced neoplasia by baseline adenoma
characteristics of multiplicity, size, histology, highgrade dysplasia, and location. These descriptive plots
(Figure 1) of the measure of the effect for various risk
factors provide a summary of the number of studies
reporting a measure of effect for a given risk factor and
the consistency and magnitude of this factor on adenoma and advanced neoplasia recurrence. The review
of evidence assessed the risk factors for adenomas and
for advanced adenomas but the discussion concentrated on the factors affecting advanced adenomas. The
definition of advanced adenoma differs from study to
study.36 The most encompassing definition included
any adenoma sized 1.0 cm or larger, any villous component (ie, nontubular), high-grade dysplasia, or invasive cancer.
Given the concern in detecting colorectal cancers at
surveillance, the number of colorectal cancers detected by
time under surveillance is cited whenever these data were
included in the published study. Special characteristics of
the study population and selection for the cohort were
also noted in the appendix (see supplemental material
online at www.gastrojournal.org).
POSTPOLYPECTOMY SURVEILLANCE
1875
Results of the Literature Review
and Rationale for the Guidelines
Certain characteristics of colorectal adenomas at
baseline colonoscopy are associated with the rate of adenoma detection and the histologic severity of subsequent
adenomas. These data can be used as the basis for decisions about safe and effective postpolypectomy surveillance intervals by stratifying patients into lower-risk and
higher-risk groups for future advanced adenomas. The
available body of evidence is the basis for these recommendations.
Quality of Baseline Colonoscopy
Baseline adenoma characteristics play a major role
in determining appropriate postpolypectomy surveillance intervals. Characteristics of the baseline colonoscopy are also an important predictor for subsequent
neoplasia. The baseline colonoscopy needs to be of high
quality for the baseline adenoma characteristics to be
used for planning surveillance intervals. As defined by
the US Multi-Society Task Force, a high-quality colonoscopy reaches the cecum, has little fecal residue, and has
a minimum time of withdrawal from the cecum of 6 –10
minutes.37 Baseline colonoscopy without a good clearing
of the colon places the patient at increased risk for
subsequent neoplastic findings.38 Adenomas, advanced
adenomas, and cancers are missed by colonoscopy.39 – 42
Sensitivity could be increased by continuing quality
improvement programs for the performance of colonoscopy.37 Trials designed specifically to evaluate surveillance, in which colonoscopy is performed by experienced
endoscopists, such as the National Polyp Study have
shown that a low incidence of cancer can be achieved in
postpolypectomy patients.5,25,43 The National Polyp
Study required meticulous clearing at the initial baseline
with repeat colonoscopy if this was not achieved with
high confidence.
On the other hand, studies designed for other purposes, such as the pooled chemoprevention studies reported by Robertson et al,20 and community studies
clearly show that higher miss rates commonly occur.39
Incomplete removal of large sessile polyps, particularly
by piecemeal polypectomy, could contribute to a higher
subsequent incidence of a colon cancer as in the chemoprevention trials.20,44 Atkin et al7 also showed that inadequate removal of sessile rectosigmoid adenomas at
baseline was associated with a marked increase in risk for
rectal cancer in a rigid sigmoidoscopy study. The National Polyp Study exclusion of patients with sessile
adenomas larger than 3.0 cm and provision for individualized follow-up evaluation for these patients could be
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GASTROENTEROLOGY Vol. 130, No. 6
May 2006
another factor that contributed to the low incidence of
cancer during the follow-up period in this study.5 Loeve
et al21 assessed colorectal cancer incidence after adenoma
detection in Holland based on 78,473 patients and found
that colorectal cancer incidence was not greatly reduced
until 5– 6 years after the initial diagnosis, and attributed
the lack of earlier effect to inadequate removal of adenomas when initially diagnosed. It is therefore important to
consider early and late-appearing cancers separately in
postpolypectomy trials to separate true incidence reduction from missed cancers. This point is shown in the
chemoprevention trials in which a large proportion of
cancers were found early; this was probably caused in
part by the inadequate removal of large adenomatous
polyps. For example, 9 of 19 cancers in the study of
Robertson et al20 were found within 26 months of the
initial colonoscopy.
Characteristics of Baseline Adenomas as
Predictors of Subsequent Advanced
Adenomas
Multiplicity. Multiplicity at baseline has been
shown to predict subsequent detection of advanced adenomas (see appendix in supplemental material online at
www.gastrojournal.org and Figure 1). Of the RCTs, the
National Polyp Study,25 the European fiber and calcium
study,29 and the pooled analysis of chemoprevention
studies20 showed that multiplicity conferred an increased
risk for advanced neoplasia at surveillance. The pooled
analysis did not report ORs but did report a significant
difference in mean number of prior lifetime adenomas at
baseline in those with and without advanced neoplasia at
surveillance. Neither the wheat bran study described by
Martinez et al28 nor the chemoprevention study presented by van Stolk27 noted a significant association
between baseline multiplicity and the detection of advanced adenoma at follow-up evaluation. However, 35%
of subjects in the study by Martinez et al28 had prior
POSTPOLYPECTOMY SURVEILLANCE
1877
adenomas, so that prior colonoscopies may have reduced
the number of adenomas detected at the index colonoscopy for study accrual. Van Stolk27 showed that individuals with 3 or more adenomas at baseline were more
likely than those with 1 or 2 adenomas at baseline to
have an adenoma detected at surveillance (OR, 2.25;
95% confidence interval [CI], 1.20 – 4.21), but found no
adenoma characteristic predictive of advanced adenomas
at surveillance. They noted, however, that the study had
limited power to detect risk factors for advanced
neoplasia.
The observational cohort studies also showed that
multiplicity was a risk factor for subsequent advanced
adenomas and cancer. Atkin et al7 followed-up a cohort
of patients who initially had rectosigmoid adenomas
removed but with no further intervention in the colon for
an average of 13.8 years. They showed that having 2 or
more rectosigmoid adenomas compared with 1 rectosigmoid adenoma at baseline was associated with an increased risk for subsequent colon cancer but not for
subsequent rectal cancer. Noshirwani et al31 reported
that the number of adenomas at baseline was related to
an increased risk (OR, 1.25; 95% CI, 1.13–1.38) for
advanced adenomas at surveillance in a cohort from the
Cleveland Clinic.
Size. Adenoma size larger than 1 cm also was
shown to predict metachronous advanced adenomas in
the wheat bran study.28 However, the other 4 RCTs did
not find adenoma size at baseline to be an independent
predictor of advanced neoplasia at surveillance. Adenoma
size was important in 7 of 8 of the observational cohort
studies assessing advanced neoplasia. Loeve et al21 did
not present data on adenoma size. In a rigid sigmoidoscopy study, Atkin et al7 reported that there was a significant trend (P ⬍ .002) for increased risk for subsequent colon cancer with increasing size of the
rectosigmoid adenoma at baseline. The standardized in-
4™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™
Figure 1. These graphs show the associations between adenoma characteristics at baseline and subsequent risk for (A) adenomas and for (B)
advanced adenomas or colorectal cancer. The dotted line separates the results from the RCTs of surveillance and chemoprevention from the
results from the observational cohort studies. Within the 2 groupings the studies are listed by year published. The graphs are presented for the
baseline risk factors of adenoma multiplicity (ⱖ3), adenoma size (ⱖ1.0 cm), adenoma histology (tubulovillous or villous), (A) high-grade
dysplasia, and proximal location (B). The left column is for the risk with respect to adenomas at surveillance, and the right column is for risk with
respect to advanced neoplasia. The studies differ with respect to the classification levels of the risk factors and on the definition of advanced
neoplasia. The specification of each study is given in the appendix (see supplemental material online at www.gastrojournal.org). The studies also
cover different periods of follow-up evaluation and use different measures of effect such as ORs, relative risks, hazard ratios, and SIRs as noted
in the appendix (see supplemental material online at www.gastrojournal.org). The term relative risk is used on the horizontal axis of the figure
to represent these different measures of effect. The referent category for the ORs, relative risks, and hazard ratios is the lowest risk category.
These estimates are denoted by black circles. Multivariate estimates are used when available. In 2 studies,7,21 SIRs were reported and are
denoted by black squares. The referent category for the SIR is the general population. Note that Avidan et al34 and Noshirwani et al31 used the
number of adenomas, not more than 3 adenomas. CC, colon cancer; RC, rectal cancer. Relative risk represents the OR, relative risk, hazard ratio,
or SIR as summarized for each study in the appendix (see supplemental material online at www.gastrojournal.org).
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WINAWER ET AL
cidence ratio for colon cancer was 1.5 (95% CI, 0.8 –2.4)
in patients with baseline adenomas less than 1 cm in size,
increased to an SIR of 2.2 (95% CI, 1.1– 4.0) for 1- to
2-cm adenomas, and further increased to an SIR of 5.9
(95% CI, 2.8 –10.6) for adenomas larger than 2 cm.
Increasing size of the rectosigmoid adenomas at baseline
also showed a significantly increasing trend of an increase
in SIR for rectal cancer even though the individual SIRs
for rectal cancer by adenoma size were not statistically
different from the general population risk. Yang et al,30
also in a sigmoidoscopy study, showed that larger adenoma size was related to subsequent risk for advanced
neoplasia at surveillance with an RR of 2.4 (95% CI,
1.3– 4.6) for size 0.6 –1.0 compared with size 0.5 cm or
smaller and an RR of 4.4 (95% CI, 1.9 –10.2) for size
greater than 1.0 cm at baseline. Noshirwani et al31
showed that a baseline adenoma of 1 cm or larger compared with less than 1 cm conferred an OR of 3.68 for
subsequent advanced neoplasia. Bertario et al12 found
that patients with adenomas larger than 2 cm compared
with 2 cm or smaller at baseline had a hazard ratio of 4.0
(95% CI, 1.1–14.4) for the development of follow-up
advanced adenomas. Lieberman and Weiss,24 reporting
the 5-year follow-up results from the VA Cooperative
Study 380, found that the percentage of patients with
advanced neoplasia was higher in those with baseline
adenomas of 1.0 cm or larger (2.6%) compared with
those less than 1.0 cm (0.4%) over 5 years of surveillance.
Although the majority of studies reported size to be a
significant factor, some did not. Neither van Stolk27 nor
Bonithon-Kopp29 found size to be a significant predictor
of metachronous advanced adenomas. Incomplete removal of large polyps identified at baseline could be a
reason that larger size was a strong predictor of subsequent advanced neoplasia in these studies.
Histology. Histologic type of adenoma at baseline
was not a significant predictor of advanced neoplasia in
the randomized trials but was for several of the observational cohorts. Histology is a particularly difficult predictor to evaluate because of the somewhat subjective
nature of classifying tubular, tubulovillous, and villous
adenomas.45 Atkin et al,7 in a rigid sigmoidoscopy study,
showed that tubulovillous histology at baseline was associated with an SIR of 3.8 (95% CI, 2.2– 6.0) and
villous histology had an SIR of 5.0 (95% CI, 2.2–9.9) for
the detection of subsequent colon cancer. Histology at
baseline was also an important predictor for subsequent
rectal cancer risk in this study. In another sigmoidoscopy
study, Yang et al30 reported that villous or tubulovillous
histology at baseline conferred an RR of 8.34 (95% CI,
3–16.0) for the detection of advanced neoplasms (rectal
cancer, or adenoma with severe dysplasia) at follow-up
GASTROENTEROLOGY Vol. 130, No. 6
evaluation. Loeve et al21 reported a significant trend for
increasing risk for colorectal cancer at surveillance in
relationship to increasing villous component or carcinoma in situ compared with tubular histology.
High-grade dysplasia is related to larger adenoma size
and villous component at baseline and is an important
predictor for subsequent advanced neoplasia in 3 of the
observational cohort studies.7,24,30 By definition all adenomas have some level of dysplasia. In the past, dysplasia
has been classified as mild, moderate, severe, or carcinoma in situ. Currently, severe dysplasia or carcinoma in
situ are considered the equivalent of high-grade dysplasia
and mild or moderate dysplasia are considered the equivalent of low-grade dysplasia. For the purposes of this
analysis, wherever possible, the risks are assessed for
high-grade and low-grade dysplasia. Atkin et al7 found
an increasing degree of dysplasia was associated with an
increasing risk for subsequent colon cancer with an SIR
of 3.3 (95% CI, 1.1– 8.0) for severe dysplasia in baseline
adenomas. Yang et al30 reported ORs of 5.9 (95% CI,
2.6 –13.5) and 14.4 (95% CI, 5.0 – 41.4), respectively,
for the development of subsequent advanced neoplasia
(rectal cancer or severe dysplasia) in patients with moderate and severe dysplasia at baseline. Lieberman and
Weiss,24 in the VA Cooperative Study, determined that
10.9% of patients with high-grade dysplasia in adenomas of any size at baseline had advanced neoplasia over
the 5-year surveillance period compared with 0.6% in
those with tubular adenomas less than 1.0 cm lacking
high-grade dysplasia.
Location. Martinez et al28 reported that a proximal adenoma at baseline was associated with an increased
risk for subsequent advanced adenomas. The OR was
1.65 (95% CI, 1.02–2.67) for baseline proximal adenomas only vs distal adenomas only, and the OR was 2.69
(95% CI, 1.34 –5.42) for proximal and distal adenomas
vs distal adenomas only at baseline. Similarly, BonithonKopp et al29 reported an OR of 2.63 (95% CI, 1.31–5.3)
for subsequent advanced neoplasia for patients with a
proximal compared with no proximal location of baseline
adenomas.29 In the observational cohort study of Loeve21
using large registry databases, the risk of colorectal cancer at surveillance was slightly lower for patients with
colon adenomas at baseline than rectal adenomas.
Other risk factors: patient age, sex, history of
polyps, and family history of colorectal cancer. In their
RCTs, Martinez et al28 and Bonithon-Kopp et al29 reported an increasing risk for subsequent neoplasia with
increasing age. Age was used frequently as a control
variable in the analyses without an explicit risk factor
presented for the age effect. Martinez et al28 and Bonithon-Kopp et al29 reported an increased risk for men for
May 2006
advanced neoplasia at surveillance. Sex also was used
frequently as a control variable in the analyses without an
explicit risk factor presented for the sex effect.
Both Martinez et al28 and Bonithon-Kopp et al29
noted that a history of polyps before the baseline adenoma was associated with an increased risk for advanced
neoplasia at surveillance. Although it is not always possible to determine whether prior polyps are adenomatous
polyps, the presence of prior polyps can be considered as
an additional risk factor. The effect of prior adenomas or
other polyps on subsequent risk was not considered in all
studies. When noted in the reviewed studies, the percentage of patients in a study with prior adenomas or
other prior polyps is included in the appendix (see supplemental material online at www.gastrojournal.org).
Family history of colorectal cancer and adenomas at a
young age46 is an established risk factor for the development of colorectal cancer.47– 49 However, few studies have
addressed specifically the relationship between family
history and metachronous advanced adenomas in postpolypectomy patients. The National Polyp Study showed
that a family history of colorectal cancer in patients age
60 or older predicted a 4.8-fold increased risk for advanced adenomas at follow-up evaluation.26 Fossi et al32
noted that a family history of colorectal cancer in a
first-degree relative was a risk factor for adenomas at
surveillance, but the study did not report on risk factors
for advanced adenomas at surveillance. As noted previously, Martinez et al28 and Bonithon-Kopp et al29 both
reported proximal adenomas at baseline as predictors of
subsequent advanced neoplasia. Proximal adenomas are
associated with family history of colorectal cancer.49 It is
possible that these studies also might have had an increased risk for advanced adenoma because of the association of family history of colorectal cancer with proximal
adenomas.
Summary of baseline predictors. The totality of
evidence suggests that multiplicity (ⱖ3 adenomas), size
(ⱖ1 cm), villous features, and high-grade dysplasia are
predictors of future advanced adenomas or cancers. Family history and proximal location also may predict metachronous advanced adenomas, but have not been well
studied. Analysis of the relative importance of each of
these predictors is complicated by their interrelationships. Consequently, multivariate analysis for some studies may find that size and histology45 are the most
important whereas others may report that multiplicity is
the most important.
There is a consensus among many of the studies that
the group at lower risk for subsequent advanced adenomas has only 1 or 2 adenomas, all less than 1 cm in size
with no high-grade dysplasia or villous features. The risk
POSTPOLYPECTOMY SURVEILLANCE
1879
for colon cancer in such low-risk patients, over an average
of 14 years, has been shown in a rigid sigmoidoscopy
polypectomy study to be similar to the average-risk
population.7
In colonoscopy studies patients have been followed-up
for only 5– 6 years after colonoscopic polypectomy to
assess their subsequent risk for neoplasia.24,25 Sigmoidoscopic polypectomy without colonoscopic assessment is
insufficient to establish colonoscopic surveillance intervals. In the Atkin et al7 study, colon risk was assessed in
an anatomic area where polypectomy was not performed
(ie, above the rectosigmoid). Postpolypectomy surveillance guidelines ideally should be based on colonoscopic
follow-up evaluation of patients who have had colonoscopic polypectomy. Based on the available evidence, we
can project that apparently low-risk patients can wait 5
and possibly 10 years for repeat colonoscopy. However,
further evaluation of this low-risk group is required to
confirm the safety of these intervals.
For rarer events such as colorectal cancer at surveillance, and even for adenomas in the smaller studies, the
confidence intervals on colorectal cancer or advanced
neoplasia may be relatively wide. Consequently, a nonstatistically significant result does not rule out that this
factor has no impact on risk for surveillance findings.
Discussion
These guidelines are based on all of the available
evidence, clinical experience, knowledge of the adenomacarcinoma sequence, and expert opinion. They are intended to be used by clinicians as a guide in their
approach to postpolypectomy surveillance, taking into
consideration clinical judgment in patient comorbidities,
patient preferences, and family history. The differences
between these guidelines and prior ones are shown in
Table 1. The detailed evidence for these guidelines are
presented in the literature review summarized by the
appendix (see supplemental material online at www.
gastrojournal.org) and Figure 1.
There is strong evidence that the adenoma cohort can
be stratified according to the risk for development of
subsequent advanced adenomas. Recommendations for
surveillance intervals in persons with multiple adenomas
and those with advanced adenomas are based primarily
on the National Polyp Study,25 an RCT, and observational cohort studies. Recommendations in the low-risk
group of 1 to 2 small tubular adenomas are based on the
low incidence of advanced adenomas in observational
cohort studies and the National Polyp Study25 over 3- to
6-year intervals and the observation by Atkin et al7 that
persons with small tubular adenomas are not at increased
1880
WINAWER ET AL
risk for developing colorectal cancer. In our opinion, the
data from observations of cohort studies supports an
interval of at least 5 years in this low-risk group; however, we reasoned that based on the data from Atkin et
al,7 informed physicians and their patients could conclude that a 10-year interval, similar to that used in the
average-risk population, also would be acceptable. The
recommendation to perform short-interval follow-up
evaluation in patients with 10 or more adenomas is based
on the increased probability of missed lesions in patients
with numerous adenomas. The recommendation to perform very short interval follow-up evaluation in patients
with large sessile polyps removed piecemeal is the repeated observation that a significant fraction of these
polyps are removed incompletely by the initial polypectomy. Recommended intervals in hereditary nonpolyposis colorectal cancer (HNPCC) are based on the known
rapid transformation through the adenoma carcinoma
sequence in these patients.50
The present collaborative effort between the US
Multi-Society Task Force on Colorectal Cancer and the
American Cancer Society was based on several considerations. The gradual increase in screening and the marked
increase in screening colonoscopy are creating a large
subset of the population that will require surveillance
based on adenoma detection. Both societies felt the need
to update the guidelines for the follow-up of these patients, according to the latest evidence. Recent surveys
have shown that 50% of endoscopists are not following
previously published guidelines for postpolypectomy
surveillance.51,52 It was believed that a consensus by the
2 organizations would strengthen the recommendations
and increase their use.
From the 1970s to the 1990s, annual follow-up
colonoscopy was common practice after polypectomy and
there were no guidelines available that addressed how
clinicians should best follow-up these patients. In 1993,
a report from the National Polyp Study showed that it
was safe to defer the first follow-up examination for 3
years.25 This evidence, along with the knowledge of the
long natural history of the adenoma-carcinoma progression, led to guidelines in 1997 that recommended a
3-year interval for the first follow-up examination after
removal of adenomas.15,16 Practice began to evolve along
the lines of this evidence. Guidelines have been used in
the courts of law as indicating the standard of practice.53
Recent guidelines have introduced the concept of risk
stratification of patients at the time of polypectomy into
those more likely or less likely to develop subsequent
serious neoplasia.13 In addition, the concept of the advanced adenoma as a surrogate biological indicator of
cancer risk has been adopted.36 Colorectal cancer would
GASTROENTEROLOGY Vol. 130, No. 6
be a more ideal outcome measure. However, the advanced adenoma was adopted as an early outcome measure of efficacy because a much longer period of time
would be required for conclusions to be drawn if cancer
were used as the outcome measure. This reasoning is
supported by several studies that have shown the relationship between advanced adenomas and cancer.45,54,55
A uniform definition of the advanced adenoma has not
yet been established clearly, but most include adenomas
with a size 1 cm or larger, any villous histology, or
high-grade dysplasia.
Several studies have examined factors that could predict the future risk for advanced adenomas including:
number, size, histology, and location of baseline adenomas; patient age; and family history of colorectal cancer.
Most of the studies that assessed risk factors for advanced
adenomas at surveillance either were RCTs of surveillance,25 chemoprevention trials,20,27–29 a prospective surveillance study,24 or registry-based observational cohort
studies of patients returning for surveillance with lessstructured follow-up evaluation outside the context of a
clinical trial.7,12,21,30,31,33,35 The most consistent evidence
for predicting subsequent advanced adenomas indicates
that multiplicity, size, villous histology, and high-grade
dysplasia are the important factors at baseline. Based on
these factors, patients can be stratified at the time of
colonoscopy into lower or higher risk for subsequent
advanced adenomas. The strongest studies for evaluating
predictive factors for future neoplasia after polypectomy
are those designed specifically as postpolypectomy surveillance studies such as the National Polyp Study. Chemoprevention randomized trials were designed to assess
the drug intervention effect with less of an emphasis on
determining optimal surveillance intervals.
Patients who have had a polypectomy and long-term
surveillance have been shown to have a reduced incidence
of colorectal cancer.5–12 When one separates out the effect
of initial polypectomy from the subsequent surveillance,
modeling has shown that more than 90% of the reduced
incidence over the first 5– 6 years is the result of the
initial polypectomy. However, there is a subgroup that
can be identified as having a higher risk for subsequent
cancer by using the advanced adenoma as a surrogate
marker.56 These observations support the concept of
stratifying patients by baseline factors so that the group
at increased risk can be identified for more intensive
surveillance and the group at lower risk can be identified
for less intensive surveillance. Reduction in the intensity
of surveillance could free up endoscopic resources that
could be shifted to screening and diagnosis, thereby
increasing the benefit and reducing the procedural risk.
May 2006
The use of fecal occult blood testing (FOBT) after
colonoscopy in postpolypectomy patients has been reported to be a widespread practice (38% of patients had
FOBT after adenoma removal at colonoscopy).57 The
National Polyp Study has shown that the use of FOBT
after colonoscopy results in a substantial number of
unnecessary colonoscopies; 77% of colonoscopies performed to evaluate positive surveillance FOBT results
detected no advanced adenomas or cancer (ie, the positive
predictive value was 23%).58 In a recent report by Bampton et al59 of 785 patients who had a recent surveillance
colonoscopy, the positive predictive value for an immunochemical FOBT was 27%. This was in a high-risk
cohort composed of patients with a history of colonic
neoplasia or with a strong family history. A lower positive predictive value would be expected in a lower-risk
population. The possible benefit of FOBT in patients
having surveillance colonoscopies needs further study,
but with the present available evidence this should be
discouraged.
In the present guidelines, recommendations for the
lower risk group are intentionally flexible because follow-up colonoscopy studies are limited to 5– 6 years.24,25
Some physicians and patients may elect to have a follow-up colonoscopy at 5 years because they wish to be
assured that future risk has been reduced to less than that
of the average-risk population. Others may feel confident
that this risk already has been reduced to less than that
of the general population by adequate clearing of the
colon and would be satisfied with either a 10-year follow-up colonoscopy or choosing other screening options
currently recommended for individuals at average
risk.13,14
Risk stratification and recommended follow-up intervals are based on the presumption that a high-quality
colonoscopy was performed at baseline. However, variable colonoscopic miss rates for adenomas and cancer
have been shown.5,20,39 – 42,60 – 62
This variability in colonoscopic baseline quality could
translate into either a lower rate of subsequent cancers
detected during surveillance as in the National Polyp
Study,5,62 or a higher rate as seen by Robertson et al20
and others39,61 For example, in the National Polyp Study,
if the baseline colonoscopy did not clear the colon with
high confidence (excellent preparation, complete
polypectomy), the examination was repeated before entering the patient into the surveillance program. Repeat
examinations were required in 13% of the patients.25
Such rigor contributed to a marked reduction in colorectal cancer incidence in the National Polyp Study that
was not observed in other studies.20,39,61 In Australian
and Japanese studies60,62 the low miss rates were calcu-
POSTPOLYPECTOMY SURVEILLANCE
1881
lated only from patients in whom the cecum was intubated. In 1 study of missed cancers,39 failure to intubate
the cecum accounted for some undetected cancers.
The quality of the baseline examination can be evaluated to some extent by the number of cancers detected
earlier vs later in a surveillance program. Thus, the major
benefit of the baseline colonoscopic polypectomy rests on
the quality of that examination.37,38 The concern by
clinicians of missed cancers can be assuaged by highquality baseline performance of colonoscopy. Protection
can never be 100%, but it is high (76%–90% colorectal
cancer incidence reduction) with high quality examination.5,37,63
There was insufficient evidence to include family history in the guidelines as a predictor of metachronous
advanced adenomas. Clearly, however, family history of
colorectal cancer in a close relative does increase the risk
for colorectal cancer in other relatives and needs further
study in the postpolypectomy setting.47– 49 Issues such as
this must be considered on an individual basis when
clinicians are determining appropriate follow-up evaluation.
Patients with a family history indicating HNPCC
require special screening and surveillance.13,15,49
HNPCC is an autosomal-dominant inherited cancer syndrome that accounts for 1%–5% of colorectal cancer
cases and is caused by germ-line mutations in 1 of 5
mismatch repair genes. The mean age for colorectal
cancer development in HNPCC is 44 years. Cancers tend
to be right sided and often are poorly differentiated,
mucus-producing tumors with intense lymphocytic infiltrates. Tumors show microsatellite instability (MSI)
and immunostaining often is negative for one of the
mismatch repair gene products. There are no clinical
criteria that are perfectly sensitive for HNPCC. The
modified Bethesda criteria perform best in this regard.64
HNPCC should be suspected when colorectal cancer or
other tumors with relative specificity for HNPCC (endometrial, ovarian, small bowel, ureter, or renal pelvis)
occur in younger people, when multiple relatives and
generations are affected, or when tumor location and
histology are suggestive. Potentially affected persons can
be screened by testing their tumors for microsatellite
instability or for mismatch repair gene products by immunostaining. Genetic testing is used when these screening tests are positive or when the clinical presentation
and family history are very strongly suggestive. Tumors
in HNPCC move through the adenoma-carcinoma sequence more rapidly than sporadic tumors.50 Definite or
potential gene carriers are screened by colonoscopy every
2 years beginning at age 20 –25 years until age 40 years,
and then annually.13 Surveillance recommendations are
1882
WINAWER ET AL
essentially the same as screening. The colon must be
cleared carefully and complete polypectomy is essential,
particularly for advanced adenomas. Patients who develop advanced adenomas and proven gene carriers can be
offered prophylactic subtotal colectomy followed by annual proctoscopy and polypectomy.
Other issues evolving in the literature that require
further study and may affect future guidelines include
different recommendations for men and for women by
age.65 Given the evolving nature of guidelines, it is
important that physicians and patients remain in contact
so that surveillance practices will reflect changes in
guidelines.
The management of patients with hyperplastic polyps
only was omitted from prior guidelines. There is no
evidence that patients with small distally located hyperplastic polyps have an increased risk for colorectal cancer
and therefore they should be prescreened as appropriate
for average-risk patients.66,67 The present guidelines state
this explicitly. It has been shown recently, however, that
hyperplastic polyps are not a homogenous histologic
category and there is accumulating evidence from molecular genetic studies that some histologic variants of
hyperplastic polyps may evolve into a unique type of
adenoma that resembles a hyperplastic polyp with dysplasia, called a serrated adenoma.68 This type of adenoma
in turn has been linked to the ultimate development of
sporadic microsatellite instability adenocarcinoma. This
form of colonic adenocarcinoma shares with HNPCC the
genetic attribute (in this case, acquired) of microsatellite
instability (sporadic microsatellite instability cancers)
because of mismatch repair deficiency. Hyperplastic polyps at risk for such a progression show atypical architectural and cytologic features, often are large, sessile, and
usually are located proximally. Other terms for these
hyperplastic polyp variants are sessile serrated adenoma or
serrated polyp with abnormal proliferation. Some investigators have suggested that complete removal and surveillance, as for typical adenomas, may be warranted in these
cases.69,70
All endoscopists must remain alert to the syndrome of
hyperplastic polyposis. Hyperplastic polyposis was defined by Burt and Jass71 for the World Health Organization International Classification of Tumors as: (1) at
least 5 histologically diagnosed hyperplastic polyps proximal to the sigmoid colon, of which 2 are greater than 1
cm in diameter, or (2) any number of hyperplastic polyps
occurring proximal to the sigmoid colon in an individual
who has a first-degree relative with hyperplastic polyposis, or (3) more than 30 hyperplastic polyps of any size
distributed throughout the colon. Studies have found an
increased risk for colorectal cancer in these patients.72,73
GASTROENTEROLOGY Vol. 130, No. 6
The pathway may be through the serrated adenoma.69,74,75 The magnitude of the increased risk has not
been determined. A recent case series of 15 patients
found no cancer developed within 3 years of follow-up
evaluation.76 The optimal management of hyperplastic
polyposis has not yet been defined and requires further
study.
Technologic advances such as computed tomography
colonography (also known as virtual colonoscopy, which
uses computed tomography scan technology), chromoendoscopy (endoscopy with dye spraying of the mucosa),
narrow band imaging (a high-resolution endoscopic technique that enhances the fine structure of the mucosal
surface without dye), and magnification endoscopy (realtime magnification of endoscopic images) may one day be
shown to be important in postpolypectomy surveillance.77– 81 Some of these techniques may have a special
role in detecting flat adenomas.82,83 However, at this
time, there is insufficient evidence that any of these
techniques should be part of routine postpolypectomy
surveillance.
In summary, guidelines are dynamic and based on the
evidence currently in the literature, understanding of the
adenoma carcinoma sequence, and expert opinion.
Guidelines must be updated as new evidence becomes
available. The committee identified a number of areas of
uncertainty and considers the following to be among the
important questions for further study.
Questions to Be Addressed
1. What are the reasons that guidelines are not followed more widely?
2. How can adherence to quality control indicators at
baseline colonoscopy be encouraged to reduce the
miss rate of advanced adenomas and colorectal cancers?
3. Will emerging studies with longer colonoscopy follow-up times support the safety of lengthening surveillance intervals?
4. What is the appropriate management and surveillance of the hyperplastic polyposis syndrome?
5. What is the appropriate surveillance of patients who
have had an adenoma removed in piecemeal fashion?
6. Which definition of advanced adenoma is associated
most strongly with subsequent cancer?
7. In the setting of postpolypectomy surveillance, what
is the role of family history in predicting advanced
adenomas and colorectal cancer?
8. What roles will chromoendoscopy, magnification
endoscopy, narrow band imaging, and computed
May 2006
9.
10.
11.
12.
13.
14.
15.
16.
tomography colonography play in postpolypectomy
surveillance?
How can molecular genetic information help to
stratify risk in patients with adenomatous polyps?
How can access to colorectal cancer screening and
appropriate surveillance be increased?
What is the usefulness of guaiac-based, or immunochemical FOBT, in postpolypectomy surveillance?
What is the usefulness of stool DNA mutation
testing in postpolypectomy surveillance?
What is the importance of detecting flat adenomas?
What is the importance of detecting serrated adenomas?
How do new insights in link between serrated polyps and microsatellite instability cancers impact surveillance practices?
What surveillance guidelines are appropriate for patients with atypical hyperplastic polyps, particularly
if large, proximally located, or multiple, and serrated adenomas?
POSTPOLYPECTOMY SURVEILLANCE
9.
10.
11.
12.
13.
14.
15.
Appendix
Supplementary data
Supplementary data associated with this article
can be found, in the online version, at doi:10.1053/
j.gastro.2006.03.012.
16.
17.
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Address requests for reprints to: Sidney J. Winawer, MD, Gastroenterology and Nutrition Service, Department of Medicine, Memorial
Sloan-Kettering Cancer Center, New York, New York 10021. e-mail:
winawers@mskcc.org; fax: (212) 639-2766.