Downloaded from gut.bmj.com on November 30, 2011 - Published by group.bmj.

com
Gut Online First, published on November 22, 2011 as 10.1136/gutjnl-2011-300295
Colorectal cancer

ORIGINAL ARTICLE

Long-term risk of colorectal cancer after adenoma

1
INSERM, UMR 866, Dijon,
France
2
Université de Bourgogne,
Registre Bourguignon des
Cancers Digestifs, Dijon, France
3
CHRU Dijon, Dijon, France
4
5
INSERM, CIE1, Dijon, France
CHRU Dijon, Centre
d’Investigation
clinique-Epidémiologie clinique,
Dijon, France
Correspondence to
Dr Vanessa Cottet, INSERM,
UMR 866, Faculté de Médecine,
BP 87900, F-21079 Dijon Cedex,
France;
vanessa.cottet@u-bourgogne.fr
Revised 15 September 2011
Accepted 16 September 2011
removal: a population-based cohort study
Vanessa Cottet,1,2,3 Valérie Jooste,1,2 Isabelle Fournel,1,2 Anne-Marie Bouvier,1,2,3,4,5
Jean Faivre,1,2,3 Claire Bonithon-Kopp1,2,4,5
ABSTRACT
Background Previous studies examining the incidence of
colorectal cancer after polypectomy have provided
discordant findings. The aim of this study was to
compare the risk of colorectal cancer after adenoma
removal in routine clinical practice with the risk in the
general population.
Design Cohort study based on detailed data from
a population-based registry that has collected all cases
of both colorectal cancers and adenomas diagnosed in
a clearly-defined population since 1976.
Setting French administrative area of Côte-d’Or
(Burgundy).
Methods Residents of the area diagnosed for the first
time with colorectal adenoma between 1990 and 1999
were included (n¼5779). Initial and follow-up data until
December 2003 were used to calculate the colorectal
cancer standardised incidence ratio (SIR) and cumulative
probabilities after adenoma removal.
Results After a median follow-up of 7.7 years, 87
invasive colorectal cancers were diagnosed whereas 69
cases were expected. Compared with the general
population, the overall SIR was 1.26 (95% CI 1.01 to
1.56). The risk of colorectal cancer depended on the
characteristics of the initial adenoma (SIR 2.23 (95% CI
1.67 to 2.92) for advanced adenomas and 0.68 (95% CI
0.44 to 0.99) for non-advanced adenomas). In cases of
advanced adenomas, the SIR was 1.10 (95% CI 0.62 to
1.82) in patients with colonoscopic follow-up and 4.26
(95% CI 2.89 to 6.04) in those without. The 10-year
cumulative probabilities of colorectal cancer were,
respectively, 2.05% (95% CI 1.14% to 3.64%) and 6.22%
(95% CI 4.26% to 9.02%).
Conclusions In routine practice, the risk of colorectal
cancer after adenoma removal remains high and
depends both on initial adenoma features and on
colonoscopy surveillance practices. Gastroenterologists
should encourage patients to comply with long-term
colonoscopic surveillance.
BACKGROUND
In France, as in other European countries and in
North America, colorectal cancer is the second most
common cancer with an estimated 37 400 new
cases in 2005, and the second most common cause
of death by cancer.1 2 There is indirect evidence that
most cancers arise from an adenoma, a very
common lesion, in a multistep process. Adenomas
>10 mm in diameter with high-grade dysplasia or
a villous component have a high potential for
malignant transformation.3
Significance of this study
What is already known about this subject?
< Previous prospective studies suggest a marked
decrease in the risk of colorectal cancer after
adenoma removal.
< Such studies were conducted under highly
standardised conditions among selected
patients.
< The effectiveness of endoscopic adenoma
removal is less clear in population-based
studies.
What are the new findings?
< In routine clinical practice, the risk of colorectal
cancer after advanced adenoma removal
remained higher than in the general population,
but the risk was reduced after non-advanced
adenoma.
< Follow-up colonoscopy seems to be effective in
reducing the risk of colorectal cancer among
patients with adenoma from the general
population.
< Compliance with colonoscopic surveillance has
to be improved among patients with adenoma.
How might it impact on clinical practice in the
foreseeable future?
< This study reinforces the importance of careful
and long-term surveillance, particularly among
patients with advanced adenoma.
< Improving the compliance of adenoma patients
with guidelines on colonoscopic surveillance is
a major challenge for general practitioners and
gastroenterologists.
Although colonoscopy is the most sensitive
method for detecting and removing colorectal
adenomas, it carries some risks for the patient, it is
costly for society and its acceptability is sometimes
low. Thus, in France, as in many countries, colono-
scopy is only used in symptomatic patients, indi-
viduals with positive faecal occult blood tests or
those at high risk, particularly with a family or
personal history of colorectal cancer.4 Surveillance
colonoscopy is also recommended in individuals who
have had one or more adenomas removed at colo-
noscopy because of their increased risk of developing
metachronous colorectal neoplasms.4 5 National
guidelines on post-polypectomy surveillance were

Cottet V, Jooste
Copyright V, Fournel
Article I, et al. (or
author Gut (2011).
theirdoi:10.1136/gutjnl-2011-300295 1 of 7
employer) 2011. Produced by BMJ Publishing Group Ltd (& BSG) under licence.
 Downloaded from gut.bmj.com on November 30, 2011 - Published by group.bmj.com
Colorectal cancer
produced in 1998 by the French National Consensus Conference.6
However, before this date, professional societies and experts
published recommendations which were similar to those
published in 1998 and used by most gastroenterologists.7 8 A
recent pooled analysis of eight prospective studies with scheduled
surveillance colonoscopies showed that, during a median follow-
up period of 47.2 months, 11.2% of patients with adenoma were
diagnosed with advanced colorectal adenomas at surveillance
colonoscopy, and 0.6% with invasive cancer.9
Previous studies that examined the risk of colorectal cancer
after adenoma removal provided discordant findings, largely
explained by differences in study design, in studied popula-
tions, or in reference groups.10e22 Moreover, some of these
studies performed under highly standardised conditions did not
reflect the reality of routine adenoma removal and follow-up
practices. We hypothesise that, given current colonoscopic
practices, the long-term incidence of colorectal cancer could be
higher than expected in adenoma patients within the general
population, and that the excess risk may depend on the initial
characteristics of the removed adenomas and on compliance
with follow-up colonoscopy. This hypothesis is partly
supported by the results of the only recent population-based
study on the topic which suggested that Dutch patients with
adenoma were at increased risk of colorectal cancer compared
with the general population.11 However, this study did not
provide detailed data on initial adenoma characteristics nor
information on colonoscopic surveillance practices in the
general population. The advantage of the population-based
Registry of Côte-d’Or is that it has collected detailed data on all
cases of both colorectal cancers and adenomas diagnosed in a
well-defined population. Based on these data, the aim of
this study was to estimate the risk of colorectal cancer in
patients with adenoma within the general population
followed-up in routine practice, both overall and according to
the initial characteristics of the patients and adenomas and to
colonoscopic follow-up practices.
Figure 1 Study flow diagram.
770 excluded
(personal history of colorectal tumours, HNPCC, colorectal
polyposis, inflammatory bowel disease)
452 with follow-up < 1 year
42 with colorectal cancer diagnosed during the first
year after adenoma.
Baseline advanced adenoma
(n=1899)
53 CRC
Follow-up colonoscopy (n=1046)
→ 15 CRC diagnosed
No follow-up colonoscopy (n=633)
→ 31 CRC diagnosed
Unknown (n=220)
→ 7 CRC diagnosed
2 of 7
METHODS
Study design
Patients were identified from the population-based registry of
colorectal polyps in Côte-d’Or (Burgundy, France), which
includes data on all cases of colorectal adenomas diagnosed since
1976. There were 506 755 residents in the area covered by the
registry, according to the 1999 census.
The study population comprised all residents of Côte-d’Or
diagnosed for the first time with a colorectal adenoma between 1
January 1990 and 31 December 1999 (n¼7043).
As shown in figure 1, we excluded patients with known
familial polyposis or hereditary non-polyposis colorectal cancer
syndrome, inflammatory bowel disease, a personal history of
adenoma or colorectal cancer, or with synchronous colorectal
cancer (n¼770). Colorectal cancer or adenomas diagnosed
within 1 year of the initial colonoscopy were assumed to have
been present during the initial investigation. Thus, these lesions
were considered as being present at the first colonoscopy. This
strategy resulted in the exclusion of 42 patients who developed
colorectal cancer during the first year after adenoma diagnosis,
and patients who died or were followed-up for <1 year (n¼452).
The final analysis included 5779 patients.
Information on adenoma cases is routinely obtained from all
public and private pathology laboratories in the area. Pathology
reports were used to classify adenomas according to histological
architecture, grade of dysplasia, size and location. For patients
with multiple adenomas, the most severe adenoma was used for
classification. Advanced adenomas were defined as adenomas
with a diameter $10 mm and/or a villous component and/or
high-grade dysplasia (severe dysplasia or intramucosal carci-
noma). Adenoma location was defined according to the 10th
International Classification of Diseases for Oncology23 and clas-
sified into: proximal colon (caecum, ascending colon, hepatic
flexure and transverse colon), distal colon (splenic flexure,
descending colon and sigmoid) and rectum (rectosigmoid junction
and rectum ampulla).
7043 patients
with a first-adenoma
6273 patients
Study population
(n=5779)
87 CRC diagnosed during the follow-up
Baseline non-advanced adenoma Unknown adenoma
(n=3236) (n=644)
26 CRC 8 CRC
Follow-up colonoscopy (n=1532) Follow-up colonoscopy (n=256)
→ 11 CRC diagnosed → 3 CRC diagnosed
No follow-up colonoscopy (n=1224) No follow-up colonoscopy (n=190)
→ 11 CRC diagnosed → 4 CRC diagnosed
Unknown (n=480) Unknown (n=198)
→ 4 CRC diagnosed → 1 CRC diagnosed
Cottet V, Jooste V, Fournel I, et al. Gut (2011). doi:10.1136/gutjnl-2011-300295
 Downloaded from gut.bmj.com on November 30, 2011 - Published by group.bmj.com

Colorectal cancer

In France, colonoscopies are performed only by trained RESULTS

gastroenterologists in public or private hospital endoscopic Study population
units. The medical records of the gastroenterologists were Between 1990 and 1999, a total of 5779 patients from Côte-d’Or
reviewed to obtain missing information such as age, sex, who underwent adenoma removal for the first time were
family history of colorectal tumours, adenoma size and included. Their mean (SD) age was 61.1 (12.9) years in men and
adenoma location. For the present study, all follow-up colo- 62.2 (13.6) years in women (p<0.001). A family history of
noscopies were collected and their findings recorded until the colorectal cancer was reported in 9.8% of patients (table 1).
study end-point date (31 December 2003) or the last known During the initial colonoscopy, advanced adenomas were
follow-up date. A follow-up colonoscopy was defined as an removed in 32.9% of patients and multiple adenomas in 25.9%
examination performed between 1 year after first adenoma of patients. For patients with available information on
removal and the end-point date or the date of cancer diagnosis. completeness of colonoscopy, the examination reached the
The colonoscopy that detected colorectal cancer was consid- caecum in 86.9% of patients. Among the 3842 patients for
ered as a follow-up colonoscopy only if the patient was whom the reason for initial colonoscopy was known, the colo-
asymptomatic and if the reason for colonoscopy was noscopy was performed because of symptoms in 3364 patients
clearly stated as surveillance of previous colorectal lesions. (87.6%), a family history of colorectal cancer in 263 (6.8%),
The vital status of adenoma patients was obtained from a positive faecal occult blood test in 155 (4.0%) and individual
multiple sources including national mortality files (National screening in 60 (1.6%).
Register for the Identification of Physical Persons), gastroen-
terologists and general practitioners’ medical records, and
hospital discharge files. Follow-up information was obtained Table 1 Characteristics of patients and their adenomas
for 96.4% of the patients with adenoma included in the upon initial examination
present study. n (%)
In addition, the cancer registry collects all cases of digestive
Gender
cancers including colorectal cancers. Data are regularly
Men 3373 (58.4)
collected from public and private pathology laboratories,
Women 2406 (41.6)
university and local hospitals, the Comprehensive Cancer
Age (years)
Centre, private specialists (gastroenterologists, surgeons,
<60 2372 (41.0)
oncologists, radiotherapists), general practitioners, as well as 60e79 2933 (50.8)
from the French National Health Service and the monthly $80 474 (8.2)
review of death certificates. The quality and comprehensive- Known family history of colorectal cancer
ness of registration is certified every 4 years by an audit of the Yes 567 (9.8)
National Institute for Health and Medical Research (INSERM) No 5212 (90.2)
and of the National Public Health Institute (InVS). Cancer Reasons for initial colonoscopy
registry activities were approved by the Burgundy Medical Symptoms 3364 (58.2)
Ethics Committee and the National Commission for Data Without symptoms 478 (8.3)
Processing and Liberties (CNIL). Data from the cancer registry Faecal occult blood test 155 (2.7)
were used to identify patients with adenoma who developed Family history 263 (4.6)
metachronous cancer and to provide reference incidence data in Other 60 (1.0)
the Côte-d’Or population. The registry also allows patients Unknown 1937 (33.5)
with a history of colorectal cancer or synchronous colorectal Number of adenomas
cancer to be identified. Only invasive colorectal cancers were 1 4281 (74.1)
considered. $2 1498 (25.9)
Adenoma location
Statistical analysis Proximal only 900 (15.6)
Distal only 2603 (45.0)
Person-time was calculated for patients with adenoma over
Rectum only 1520 (26.3)
a period beginning 1 year after the date of diagnosis of first
Multiple locations 638 (11.0)
adenoma until the date of invasive colorectal cancer diagnosis
Unknown 118 (2.0)
or the date of death or the last available medical follow-up or
Maximal adenoma size*
the end-point date (December 2003), whichever came first. <10 mm 3418 (59.1)
The number of person-years was calculated by sex and 5-year $10 mm 1578 (27.3)
age group. The sex and age-specific colorectal cancer incidence Unknown 783 (13.6)
rates in the general population were obtained from the Histology*
cancer registry. The expected number of colorectal cancers Villous component 930 (16.1)
was calculated by multiplying incidence rates in the general Tubulous only 4820 (83.4)
population by the observed sex and age-specific number Unknown 29 (0.5)
of person-years at risk in the study population. The ratio Dysplasia*
of observed to expected cases of colorectal cancer was High-grade 280 (4.9)
reported as a standardised incidence ratio (SIR). The calcu- Low-grade 5486 (94.9)
lation of 95% CIs was based on the exact Poisson distribu- Unknown 13 (0.2)
tion.24 Cumulative colorectal cancer probabilities were Advanced adenomas*
calculated using the KaplaneMeier method and expressed Yes 1899 (32.9)
with 95% CI. No 3236 (56.0)
Statistical analyses were performed using STATA V.10.0 (Stata Unknown 644 (11.1)
Corporation). *Characteristics of the most affected adenoma.

Cottet V, Jooste V, Fournel I, et al. Gut (2011). doi:10.1136/gutjnl-2011-300295 3 of 7

 Downloaded from gut.bmj.com on November 30, 2011 - Published by group.bmj.com

Colorectal cancer

Overall risk of colorectal cancer after first adenoma removal
The median follow-up was 7.7 years (interquartile range (IQR)
5.2e10.5) after diagnosis of the adenoma. After exclusion of the
first year following adenoma removal, the total number of
person-years at risk was 39 712. During follow-up, 87 invasive
colorectal cancers were diagnosed in the study population
whereas 69.0 cases were expected. Thus, compared with the
general population, the risk of colorectal cancer was significantly
increased after first adenoma removal (SIR 1.26 (95% CI 1.01 to
1.56)). The median time period between first resection of
adenoma and diagnosis of invasive colorectal cancer was
4.8 years (IQR 2.8e7.7). The distribution of TNM stages in
cancer patients was 55 with stages I or II (63.2%) and 32 with
stages III, IV or unclassified (36.8%).
Risk of colorectal cancer after resection of advanced and
non-advanced adenoma
At initial colonoscopy, 1899 patients had initial advanced
adenomas and 3236 had only non-advanced adenomas (figure 1).
As indicated in table 2, among the 53 cancers diagnosed after
initial advanced adenoma, 18 (34.0%) were diagnosed 12e36
months after adenoma removal. Among patients with non-
advanced adenoma, four of 26 (15.4%) were diagnosed between
12 and 36 months.
As shown in table 2, the SIRs were noticeably different
between patients with an advanced adenoma (SIR 2.23 (95% CI
1.67 to 2.92)) and those with a non-advanced adenoma (SIR 0.68
(95% CI 0.44 to 0.99)). In patients with an advanced adenoma,
the SIRs were significantly increased regardless of sex, age,
number or location of adenomas and the time period since
adenoma diagnosis. In patients with a non-advanced adenoma,
the SIRs were consistently <1 regardless of the studied group,
even though they did not reach the significance level.
Colonoscopic follow-up
As shown in figure 1, information on colonoscopic follow-up
was available for 4881 patients (84.5%). These patients were
younger and more often had a family history of colorectal cancer
and an advanced adenoma at the baseline colonoscopy than
patients without information on colonoscopic follow-up.
Among these 4881 patients, 2834 (58.1%) had had at least one
follow-up colonoscopy. The follow-up colonoscopies revealed
that 1071 patients (37.8%) had no polyps, 636 (22.5%) had only
non-adenomatous polyps, 286 (10.1%) had developed new
advanced adenomas, 838 (29.6%) had non-advanced adenomas
and 3 (0.1%) had an invasive colorectal cancer.
Table 3 shows that colonoscopic follow-up had a marked
effect on the risk of colorectal cancer, especially in patients
with an advanced adenoma. The risk fell to that found within
the general population if patients with an advanced adenoma
had at least one follow-up colonoscopy (SIR 1.10 (95% CI 0.62
to 1.82)), while this risk was more than four times higher in
patients without follow-up colonoscopy (SIR 4.26 (95%
CI 2.89 to 6.04)). After resection of non-advanced adenomas,
the risk of colorectal cancer tended to be lower than that
found within the general population, especially when
patients had at least one follow-up colonoscopy (SIR 0.60 (95%
CI 0.30 to 1.07)), even if the SIR did not reach the significance
level.
As detailed in table 4, the overall proportion of advanced
TNM stage cancers (TNM III/IV/unclassified) tended to be
higher among patients without colonoscopic follow-up than in
the other groups. This trend was mainly due to patients with an
initial advanced adenoma; the proportion of advanced stage
cancers was 28.3% among patients with advanced adenoma
without colonoscopic follow-up and 7.5% among those with
a known colonoscopic follow-up.

Table 2 Standardised incidence ratio (SIR) of colorectal cancer after first adenoma removal according to characteristics of patients and adenomas
Patients with advanced adenomas Patients with non-advanced adenomas
Person-years at risk Observed cases SIR 95% CI Person-years at risk Observed cases SIR 95% CI
All 12 183 53 2.23 1.67 to 2.92 23 426 26 0.68 0.44 to 0.99
Gender
Men 7070 34 2.08 1.48 to 2.90 13 551 17 0.64 0.40 to 1.03
Women 5113 19 2.59 1.65 to 4.06 9875 9 0.77 0.40 to 1.48
Age (years)
<60 4396 12 3.65 1.88 to 6.37 11 538 3 0.39 0.08 to 1.13
60e79 6848 30 1.75 1.18 to 2.50 10 892 20 0.74 0.45 to 1.15
$80 940 11 3.32 1.66 to 5.95 995 3 0.84 0.17 to 2.44
Known family history of colorectal cancer
Yes 1324 7 3.76 1.51 to 7.75 2290 2 0.77 0.09 to 2.77
No 10 860 46 2.10 1.54 to 2.81 21 136 24 0.67 0.43 to 1.00
Time period after initial adenoma (months)
12e36 3640 18 2.76 1.64 to 4.37 6274 4 0.44 0.12 to 1.12
36e60 3250 16 2.61 1.49 to 4.24 5803 4 0.44 0.12 to 1.13
60e120 4516 16 1.73 0.99 to 2.80 9193 13 0.81 0.43 to 1.39
Number of adenomas
1 8409 36 2.32 1.62 to 3.21 17 570 20 0.71 0.44 to 1.10
$2 3774 17 2.07 1.21 to 3.32 5856 6 0.59 0.21 to 1.28
Adenoma location
Proximal only 1121 3 1.26 0.25 to 3.67 4158 5 0.63 0.20 to 1.47
Distal only 6200 24 2.08 1.33 to 3.09 9931 11 0.68 0.34 to 1.22
Rectum only 2634 14 2.85 1.56 to 4.78 7030 9 0.91 0.41 to 1.72
Multiple locations 2127 12 2.58 1.33 to 4.50 2001 1 0.26 0.00 to 1.47
SIR, standardised incidence ratio.

4 of 7 Cottet V, Jooste V, Fournel I, et al. Gut (2011). doi:10.1136/gutjnl-2011-300295

 Downloaded from gut.bmj.com on November 30, 2011 - Published by group.bmj.com

Colorectal cancer

Table 3 Standardised incidence ratio (SIR) of colorectal cancer after first adenoma removal according to colonoscopic follow-up
Advanced adenomas Non-advanced adenomas
Person-years at risk Observed cases SIR 95% CI Person-years at risk Observed cases SIR 95% CI
Colonoscopic follow-up
At least one colonoscopy* 7588 15 1.10 0.62 to 1.82 12 328 11 0.60 0.30 to 1.07
No colonoscopy 3259 31 4.26 2.89 to 6.04 7362 11 0.82 0.41 to 1.47
Unknown 1335 7 2.46 0.99 to 5.08 3736 4 0.61 0.17 to 1.57
*Excluding the diagnosis colonoscopy for patients who developed a symptomatic colorectal cancer.
SIR, standardised incidence ratio.

Cumulative probabilities of colorectal cancer
Overall, the cumulative probabilities of developing colorectal
cancer after adenoma removal were 0.83% (95% CI 0.62% to
1.12%) at 5 years and 1.89% (95% CI 1.49% to 2.39%) at
10 years. Corresponding figures were, respectively, 1.94% (95%
CI 1.39% to 2.70%) and 3.95% (95% CI 2.91% to 5.36%) in
patients with advanced adenomas, and 0.26% (95% CI 0.13% to
0.53%) and 0.90% (95% CI 0.58% to 1.40%) in patients with
non-advanced adenomas.
As indicated in Figure 2, the 10-year cumulative probability of
colorectal cancer in patients with an initial advanced adenoma
was 2.05% (95% CI 1.14% to 3.64%) for patients with at least
one follow-up colonoscopy, and 6.22% (95% CI 4.26% to 9.02%)
for those without. Corresponding figures in patients with non-
advanced adenomas were respectively 0.76% (95% CI 0.39% to
1.48%) and 1.37% (95% CI 0.70% to 2.65%).
DISCUSSION
This study showed that, given the usual conditions of poly-
pectomy and colonoscopic follow-up, the long-term risk of
colorectal cancer remained higher in patients diagnosed for the
first time with adenomas than in the general population. Our
study highlighted that both initial adenoma features and the
conditions of colonoscopic surveillance in routine practice
strongly affected the cancer risk. Compared with the general
population, the risk of developing colorectal cancer after poly-
pectomy only remained high in patients with advanced
adenomas and without follow-up colonoscopy. However,
patients with initial advanced adenomas could largely benefit
from colonoscopic surveillance, since the risk of cancer was
similar to that in the general population when at least one
follow-up colonoscopy was performed. The cancer risk was low
in patients with non-advanced adenomas in comparison with
the general population.
The advantage of this registry study is that it is based on
a large population of unselected patients with a long duration of
follow-up, so that it provided unbiased and accurate estimates of
Table 4 Proportion of advanced TNM stage colorectal cancers
according to the initial features of first adenomas removed and
colonoscopic follow-up
Among patients
with initial
Colorectal cancer advanced
diagnosed during Total adenomas
follow-up (N[87) (N[53)
TNM stage III/IV/unclassified 32 (36.8%) 21 (39.6%)
With colonoscopic follow-up 8 (9.2%) 4 (7.5%)
Without colonoscopic 20 (23.0%) 15 (28.3%)
follow-up
Unknown colonoscopic 4 (4.6%) 2 (3.8%)
follow-up
colorectal cancer risk, even in subgroups. Registration in the
same area of both colorectal cancers and adenomas was
performed by the same staff during the study period, which
guaranteed standardised data recording. This also allowed us to
use reference data from the same population to calculate SIRs.
Furthermore, the study population lived in an area of France
where the incidence of colorectal cancer and facilities fall within
the national average,1 and patients underwent colonoscopies in
university or general hospitals as well as in private hospitals.
Our results can therefore be broadly extrapolated to overall
clinical practice in France.
However, our study has some limitations. First, it is an
observational study that did not allow for any causal relation-
ship as a randomised controlled trial to be drawn. The purpose
of the present population-based study was to describe the reality
of routine clinical practice where patients are not always prop-
erly prepared for colonoscopy, complete resection is not always
performed and patients do not systematically undergo surveil-
lance colonoscopy. No data were available on the quality of the
colonoscopic preparation or on withdrawal time during the
endoscopic examination. In contrast to some previous studies
which included only subjects with total colonoscopy, in our
study the proportion of incomplete colonoscopy at baseline
was estimated to be 13.1% among patients with available
information on completeness of colonoscopy. In order to
consider that all diagnosed polyps had been completely removed,
data from the repeated colonoscopy performed within the year
following diagnosis were included with the baseline data. The
legitimacy of our strategy, though imperfect, is consolidated by
the results of the Dutch study showing a SIR as high as 7.9
overall, which dropped to 1.5 after exclusion of the first year.11
In our study the SIR was 1.66 (95% CI 1.38 to 1.97) for the
overall period and 1.26 (95% CI 1.01 to 1.56) after exclusion of
the first year.
Several studies have examined the risk of colorectal cancer
after polypectomy and provided discordant results. Some of
them found either no change15 18 19 or an increased risk of
colorectal cancer after polypectomy.12 20 In contrast, most
prospective studies13 16 17 21 22 and one retrospective study14
performed in selected patients enrolled in scheduled surveillance
programmes found a significant reduction in the risk of colo-
rectal cancer compared with the general population, with SIRs
ranging from 0.24 in the National Polyp study22 to 0.65 in
Among patients
with initial
a Danish study.16 These studies were sometimes based on small
non-advanced hospital series or on short follow-up periods. Expected inci-
adenomas dences were calculated from external populations which is not
(N[26) the case in population-based studies. In the National Polyp
9 (34.6%) study22 and the Italian study,14 patients with very large
3 (11.5%) adenomas at baseline were excluded. The high risk of recurrence
4 (15.4%) in such patients is well recognised and constitutes one of the
key elements behind the current recommendations for post-
2 (7.7%) polypectomy surveillance worldwide.25 26 Atkin et al showed
that the risk of rectal cancer or colon cancer was confined to

Cottet V, Jooste V, Fournel I, et al. Gut (2011). doi:10.1136/gutjnl-2011-300295 5 of 7

 Downloaded from gut.bmj.com on November 30, 2011 - Published by group.bmj.com
Colorectal cancer
Figure 2 Cumulative probabilities of
colorectal cancer according to whether
the first adenoma is advanced or non-
advanced and the presence or absence
of surveillance.
patients with advanced adenomas at baseline, whereas patients
with non-advanced adenomas had no increased risk.12 However,
in this study, as well as in the Telemark Polyp study, the first
detection of adenoma was based on rectosigmoidoscopy.12 21
Whatever the results yielded by these studies of varying quality,
they do not reflect the usual conditions of colonoscopic practice
and surveillance in the general population and thus the actual
risk incurred by patients with adenoma.
To our knowledge, only two previous population-based
studies have provided results on the topic, and both showed an
excess of colorectal cancer after adenoma removal.10 11 After
exclusion of the first year following adenoma removal, the SIR
reported was 1.77 (95% CI 1.3 to 2.2) in the Swiss study10 and
1.5 (95% CI 1.4 to 1.6) in the Dutch study.11 Our study extended
the above findings in several ways. First, we demonstrated that
the characteristics of adenomas diagnosed for the first time in
patients from the general population had a major impact on the
subsequent risk of cancer. Clearly, the overall risk of colorectal
cancer in populations with adenomas is largely dependent on
the proportion of patients with advanced adenomas. Such
detailed information was not available in the Swiss and Dutch
studies and may partially account for the slightly higher risk of
colorectal cancer reported.10 11
Second, our study suggested that a family history of colorectal
cancer may increase the risk of subsequent colorectal cancer in
patients with advanced adenomas but not in those with non-
advanced adenomas. The SIR was almost twice as high in
patients with advanced adenoma with a positive family history
compared with those with a negative history. This finding is in
line with previous reports from our group suggesting that first-
degree relatives of patients with large adenomas or of patients
with cancer had an increased risk of developing both large
adenomas and cancer.27 28
Last, our findings suggest that the benefit of colonoscopic
surveillance, demonstrated in randomised trials, could also be
observed under the usual conditions of colonoscopic practice,
especially in patients with advanced adenomas. Clearly, such
patients are intrinsically at a high risk of colorectal cancer,
probably because of an unfavourable genetic, lifestyle or envi-
ronmental background. The reduction in the SIR from 4.26
without any follow-up colonoscopy to 1.10 with follow-up
colonoscopy justifies the great benefit of colonoscopic surveil-
lance among these patients. Moreover, the proportion of
advanced TNM stage cancers tended to be lower if patients with
advanced adenomas at baseline had had a follow-up colonoscopy
(7.5% vs 28.3%). For patients with non-advanced adenomas at
baseline, their risk of colorectal cancer was similar to or lower
than that observed in the general population, with only
marginal variations due to follow-up colonoscopy.
6 of 7
Owing to the benefit of colonoscopic surveillance, the low
rate of colonoscopy among patients with a previous adenoma is
worrying. This is not specific to the area since this low
compliance with screening colonoscopy has already been
reported in studies performed all over the country.28 29
According to current guidelines, surveillance colonoscopy is
recommended at 3 years for an advanced adenoma and at 5 years
for a non-advanced adenoma. In the present study, when anal-
ysis was restricted to patients with advanced adenoma with at
least 3 years of follow-up, only 50.6% of patients had had at
least one colonoscopy within the 3 years (+6 months) following
adenoma removal (data not shown). Among patients with non-
advanced adenomas and at least 5 years of follow-up, 47.7% had
had a follow-up colonoscopy within the 5 years (+6 months)
following adenoma removal. In France, the cost of colonoscopy
to the patient is not an explanation since the examination is
almost totally reimbursed by the French health insurance
system covering 98% of the population. Further studies are
needed to understand why patients do not follow the recom-
mendations of their gastroenterologist after removal of the first
adenoma, and thus to develop appropriate strategies to improve
the acceptability of colonoscopy. It is possible that these
patients did not perceive themselves as being at risk of colorectal
cancer. A thorough evaluation of sociological and psychological
barriers would be necessary to understand the resistance of these
patients to colonoscopic follow-up and to increase their aware-
ness of the incurred risks and benefits of surveillance.
In conclusion, this study shows that, given the usual condi-
tions of colonoscopic practice and surveillance in the general
population, the risk of colorectal cancer after removal of an
adenoma remains higher than expected. The risk pattern in
patients with advanced and non-advanced adenomas reinforces
the importance of careful and long-term surveillance, par-
ticularly among high-risk patients. Improving the compliance
of patients with adenoma to guidelines on colonoscopic
surveillance is a major challenge for general practitioners and
gastroenterologists.
Acknowledgements The authors are grateful to the pathologists and the
gastroenterologists of Côte-d’Or. They also thank I Dasseux, P Demasson, J Durier,
E Lanier, M L Poillot and G Viénot for their technical assistance.
Funding This work was supported in part by the French Ministry of Health (PHRC), the
National Institute of Medical Research (INSERM), the Regional Council of Burgundy
and the ‘Fondation de France’.
Competing interests None.
Ethics approval Ethics approval was provided by Burgundy Medical Ethics
Committee and the National Commission for Data Processing and Liberties (CNIL).
Contributors VC was responsible for study design, acquisition of data, statistical
analysis, interpretation of data and manuscript writing. VJ was involved in the
Cottet V, Jooste V, Fournel I, et al. Gut (2011). doi:10.1136/gutjnl-2011-300295
 Downloaded from gut.bmj.com on November 30, 2011 - Published by group.bmj.com
statistical analysis, interpretation of data and drafting of the manuscript. IF was
involved in data analysis and manuscript editing. A-MB provided significant advice and
was involved in acquisition of data and critical revision of the manuscript. JF was
involved in study concept, interpretation of data and manuscript writing. CB-K
obtained funding and was responsible for study coordination, study design, analysis
plan, interpretation of data and manuscript writing. VC had full access to all the data in
the study and had final responsibility for the decision to submit for publication.
Provenance and peer review Not commissioned; externally peer reviewed.
REFERENCES
1. Belot A, Grosclaude P, Bossard N, et al. Cancer incidence and mortality in France
over the period 1980e2005. Rev Epidemiol Sante Publique 2008;56:159e75.
2. Ferlay J, Autier P, Boniol M, et al. Estimates of the cancer incidence and mortality in
Europe in 2006. Ann Oncol 2007;18:581e92.
3. Stryker SJ, Wolff BG, Culp CE, et al. Natural history of untreated colonic polyps.
Gastroenterology 1987;93:1009e13.
4. Agence Nationale d’Accréditation et d’Evaluation en Santé. Endoscopie
digestive basse: Indications en dehors de dépistage en population. 2004. http://
www.has-sante.fr/portail/jcms/c_272348/endoscopie-digestive-basse-indications-
en-dehors-du-depistage-en-population (accessed 10 Apr 2011).
5. Winawer SJ, Zauber AG, Fletcher RH, et al; US Multi-Society Task Force on
Colorectal Cancer; American Cancer Society. Guidelines for colonoscopy surveillance
after polypectomy: a consensus update by the US Multi-Society Task Force on
Colorectal Cancer and the American Cancer Society. Gastroenterology
2006;130:1872e85.
6. Conférence de Consensus. Prévention, diagnostic et traitement du cancer colique.
Gastroenterol Clin Biol 1998;22:S275e88.
7. Kronborg O, Fernger C. Prognostic evaluation of planned follow-up in patients with
colorectal adenomas. An interim report. Int J Colorectal Dis 1987;2:203e7.
8. Williams CB, Macrae FA. The St Mark’s neoplastic polyp follow-up study. Front
Gastrointest Res 1986;10:226e42.
9. Martinez ME, Baron JA, Lieberman DA, et al. A pooled analysis of advanced
colorectal neoplasia diagnoses after colonoscopic polypectomy. Gastroenterology
2009;136:832e41.
10. Levi F, Randimbison L, La Vecchia C. Trends in subsite distribution of colorectal
cancers and polyps from the Vaud Cancer Registry. Cancer 1993;72:46e50.
11. Loeve F, van Ballegooijen M, Boer R, et al. Colorectal cancer risk in adenoma
patients: a nation-wide study. Int J Cancer 2004;111:147e51.
12. Atkin WS, Morson BC, Cuzick J. Long-term risk of colorectal cancer after excision of
rectosigmoid adenomas. N Engl J Med 1992;326:658e62.
13. Bertario L, Russo A, Sala P, et al. Predictors of metachronous colorectal neoplasms
in sporadic adenoma patients. Int J Cancer 2003;105:82e7.
Cottet V, Jooste V, Fournel I, et al. Gut (2011). doi:10.1136/gutjnl-2011-300295
Colorectal cancer
14. Citarda F, Tomaselli G, Capocaccia R, et al. Efficacy in standard clinical practice of
colonoscopic polypectomy in reducing colorectal cancer incidence. Gut
2001;48:812e15.
15. Jonkers D, Ernst J, Pladdet I, et al. Endoscopic follow-up of 383 patients with
colorectal adenoma: an observational study in daily practice. Eur J Cancer Prev
2006;15:202e10.
16. Jorgensen OD, Kronborg O, Fenger C. The Funen Adenoma Follow-up Study.
Incidence and death from colorectal carcinoma in an adenoma surveillance program.
Scand J Gastroenterol 1993;28:869e74.
17. Lund JN, Scholefield JH, Grainge MJ, et al. Risks, costs, and compliance limit
colorectal adenoma surveillance: lessons from a randomised trial. Gut
2001;49:91e6.
18. Meagher AP, Stuart M. Does colonoscopic polypectomy reduce the incidence of
colorectal carcinoma? Aust NZ J Surg 1994;64:400e4.
19. Murakami R, Tsukuma H, Kanamori S, et al. Natural history of colorectal polyps and
the effect of polypectomy on occurrence of subsequent cancer. Int J Cancer
1990;46:159e64.
20. Simons BD, Morrison AS, Lev R, et al. Relationship of polyps to cancer of the large
intestine. J Natl Cancer Inst 1992;84:962e6.
21. Thiis-Evensen E, Hoff GS, Sauar J, et al. Population-based surveillance by
colonoscopy: effect on the incidence of colorectal cancer. Telemark Polyp Study I.
Scand J Gastroenterol 1999;34:414e20.
22. Winawer SJ, Zauber AG, Ho MN, et al. Prevention of colorectal cancer by
colonoscopic polypectomy. The National Polyp Study Workgroup. N Engl J Med
1993;329:1977e81.
23. ICD-O: International Classification of Diseases for Oncology. 3rd revision. Geneva:
World Health Organization, 1995.
24. Breslow NE, Day NE. Statistical methods in cancer research. Volume II: The design
and analysis of cohort studies. IARC Sci Publ 1987;82:1e406.
25. Bonithon-Kopp C, Piard F, Fenger C, et al; European Cancer Prevention Organisation
Study Group. Colorectal adenoma characteristics as predictors of recurrence. Dis
Colon Rectum 2004;47:323e33.
26. Martinez ME, Sampliner R, Marshall JR, et al. Adenoma characteristics as risk
factors for recurrence of advanced adenomas. Gastroenterology 2001;120:1077e83.
27. Cottet V, Pariente A, Nalet B, et al; ANGH Group. Colonoscopic screening of first-
degree relatives of patients with large adenomas: increased risk of colorectal tumors.
Gastroenterology 2007;133:1086e92.
28. Pariente A, Milan C, Lafon J, et al. Colonoscopic screening in first-degree relatives
of patients with ’sporadic’ colorectal cancer: a case-control study. The Association
Nationale des Gastroenterologues des Hopitaux and Registre Bourguignon des
Cancers Digestifs (INSERM CRI 9505). Gastroenterology 1998;115:7e12.
29. Cottet V, Pariente A, Nalet B, et al; ANGH Group. Low compliance with colonoscopic
screening in first-degree relatives of patients with large adenomas. Aliment
Pharmacol Ther 2006;24:101e9.
PAGE fraction trail=6.75
7 of 7
 Downloaded from gut.bmj.com on November 30, 2011 - Published by group.bmj.com

Long-term risk of colorectal cancer after

adenoma removal: a population-based
cohort study
Vanessa Cottet, Valérie Jooste, Isabelle Fournel, et al.

Gut published online November 22, 2011

doi: 10.1136/gutjnl-2011-300295

Updated information and services can be found at:

http://gut.bmj.com/content/early/2011/11/15/gutjnl-2011-300295.full.html

These include:
References This article cites 27 articles, 4 of which can be accessed free at:
http://gut.bmj.com/content/early/2011/11/15/gutjnl-2011-300295.full.html#ref-list-1

P<P Published online November 22, 2011 in advance of the print journal.

Email alerting Receive free email alerts when new articles cite this article. Sign up in
service the box at the top right corner of the online article.

Notes

Advance online articles have been peer reviewed, accepted for publication, edited and
typeset, but have not not yet appeared in the paper journal. Advance online articles are
citable and establish publication priority; they are indexed by PubMed from initial
publication. Citations to Advance online articles must include the digital object identifier
(DOIs) and date of initial publication.

To request permissions go to:

http://group.bmj.com/group/rights-licensing/permissions

To order reprints go to:

http://journals.bmj.com/cgi/reprintform

To subscribe to BMJ go to:

http://group.bmj.com/subscribe/