Effectofadenoma&surveillance&on& colorectal&cancer ...
Transcript of Effectofadenoma&surveillance&on& colorectal&cancer ...
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Effect of adenoma surveillance on colorectal cancer incidence: a multicentre cohort study
Wendy Atkin FMedSci OBE
Cancer Screening and Prevention Research GroupDepartment of Surgery and Cancer
Imperial College London
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• Colorectal cancer (CRC) is the 2nd most frequent cause of cancer death in Western world.
• Endoscopic removal of adenomas, precursors of most CRCs, reduces CRC incidence and mortality.
• After adenoma removal, colonoscopy surveillance is offered to those perceived to be at increased CRC risk.
• Adenoma surveillance guidelines stratify patients into risk groups based on advanced adenoma (≥ 1cm, ≥ 25% villous, high-grade dysplasia) detection at 1st surveillance
• Guidelines not supported by evidence on CRC risk
Background
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Atkin WS, Saunders BP. Gut 2002;;51 suppl 5:V6-9.;; NICE:, 2011
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US and UK adenoma surveillance guidelines & rates of advanced adenomas at 1st follow-up*
U.S. Guidelines†
Group 21-2 small, tubular w/LGD
Group 33-10 , OR ≥1 1+ cm
OR any with villous/HGD
Group 410+ adenomas
U.K. Guidelines‡
Low Risk1-2 & both small
Intermediate Risk3-4 small OR 1-2 1+ cm
High Risk5+ small OR 3+ ≥1 1+ cm
5-10 years
3 years
<3 years
No surveillance or 5 years
3 years
1 year
3.6 %
11.3 %
9.9 %
18.7 %
4.0 %
† Lieberman et al, Gastroenterology. 2012;;143:844-57 ‡ Atkin WS, Saunders BP. Gut 2002;;51 suppl 5:V6-9.;; NICE:, 2011* Martinez et al, Ann Intern Med 2012;;157:856-64
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To address following questions
• What is the CRC incidence after colonoscopic removal of intermediate risk adenomas with no surveillance?
• Is CRC risk higher than in general population?
• Does colonoscopy surveillance reduce that risk?
• Does risk vary within the intermediate risk group?
• Is colonoscopy surveillance warranted in all intermediate risk patients?
Aims of the study
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Participant flow diagramPatients with lower gastrointestinal endoscopy +/- pathology
n = 253,798
Excluded 223,539
CRC at baseline 16,081Other colonic conditions* 29,636No baseline colonoscopy 2,752Missing exam date(s) 92No adenomas 174,978
Eligible patients with adenomas n = 30,259
Low-risk: 14,522Intermediate-risk: 11,995High-risk: 2,709Not classifiable 1,033
Eligible patients with intermediate risk adenomas at baselinen = 11,995
Lost to follow-up 51
Data available for analysis:n = 11,944
*Colorectal cancer, inflammatory bowel disease, colonic resection, polyposis, hereditary risk
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• Included all patients having lower GI pathology between 1990 and 2010 from 17 hospitals.
• Identified patients having ≥1 colonoscopy and intermediate risk adenomas diagnosed
• Divided each patient’s endoscopies into “visits”, defined as: one or more endoscopies performed in close succession to complete an examination and remove all detected lesions
• Hierarchy of rules to define values for lesion characteristics (number, size, histology etc) and quality of examination
• Ascertained CRCs from hospital reports and NHS data repositories for England and Scotland and deaths from Office of National Statistics
• Censored patients at CRC Dx, death, emigration or 31 Dec 2014
Methods
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• Time at risk started at last baseline exam;; exposure to each surveillance visit started at last exam in visit.
• One minus the Kaplan-Meier estimator of the survival function used to show time to CRC diagnosis and estimate cumulative CRC incidence.
• Cox proportional hazards models used to examine the effects of surveillance and baseline patient, procedural, and polyp characteristics on long-term CRC incidence. Number of surveillance visits included as a time-varying covariate.
• Independent predictors of CRC incidence identified in a multivariable model;; backward stepwise selection with p < 0·05 in the likelihood ratio test used to determine retention of variables.
• Patients divided into lower- and higher-intermediate risk subgroups using factors identified from the multivariable model (but not age).
• Standardised incidence ratios (SIRs) reported as the ratio of observed to expected CRCs, with expected CRCs estimated using observed 2007 incidence data for England;; 95% CIs assumed an exact Poisson distribution.
Statistical methods
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• The cohort comprised 11,944 Intermediate Risk patients
• Median age at Dx 66.7 years, 55.5% male
• Baseline visit comprised 1 or 2 visits in 10,614 (89%) patients
• 6925 (58%) attended ≥ 1 surveillance
• 5019 (42%) had a baseline visit only and no surveillance
• Median follow-up time after baseline was 8 years (IQR 6-11 years)
• 210 CRCs diagnosed during 101,034 person-years of follow-up
Results
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CRC incidence and effect of surveillance visits after baseline
Visits after baseline*
n (%) CRC cases
Incidence per 105 py
Univariable HR (95% CI)
Multivariable HR (95% CI)
0 5 019 (42%) 121 233 1 1
1 3 503 (29%) 51 173 0.54 (0.39-0.77) 0.57 (0.40-0.80)
2 2 085 (18%) 22 174 0.46 (0.28-0.75) 0.51 (0.31-0.84)
≥ 3 1 337 (11%) 16 231 0.49 (0.27-0.88) 0.54 (0.29-0.99)
p = 0.0004 p = 0.0029
Atkin et al., Lancet Oncology Published online April 27,2017
* Included in models as a time-varying covariate.
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CRC incidence by baseline risk factors
Baseline risk factor n CRC cases
Incidence per 105 py
Multivariable HR (95% CI)
p value
Adenoma size (mm) 0.0335<10 1029 10 120 110-19 6857 116 198 1.97 (1.01-3.81)≥20 4058 84 246 2.28 (1.06-4.50)Adenoma dysplasia 0.0033High grade 1994 51 322 1.69 (1.21-2.36)Proximal polyps 0.0004Yes 3649 73 254 1.76 (1.30-2.38)Colonoscopy 0.0001Incomplete or not known 2928 86 299 1.80 (1.34-2.41)Bowel prep quality 0.0452Excellent or good 3956 53 159 1Satisfactory 1922 29 213 1.51 (0.95-2.39)Poor 671 16 356 2.09 (1.19-3.67)
Atkin et al., Lancet Oncology Published online April 27,2017
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CRC incidence and effect of surveillance in lower- and higher-risk subgroups
Incidence of CRC Effect of surveillanceNo. of visits
n CRC cases
Rate per 105 py
Univariable HR (95% CI)
p value
Lower-risk subgroup 0 1,411 15 101 1 (Referent) 0.22
1 937 6 85 0.54 (0.20-1.43)
≥2 731 3 80 0.36 (0.09-1.41)
Total 3,079 24 93
Higher-risk subgroup 0 3,608 106 286 1 (Referent) 0.0001
1 2,566 45 201 0.52 (0.36-0.75)
≥2 2,691 35 221 0.45 (0.29-0.70)
Total 8,865 186 247
Atkin et al., Lancet Oncology Published online April 27,2017
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Reason classified as higher-risk
Incidence of CRC Effect of surveillanceNo. of visits
n CRC cases
Rate per 105
Univariable HR (95% CI)
p value
Poor quality exam only 0 613 18 253 1 (Referent) 0.25
1 451 8 170 0.49 (0.21-1.18)
≥2 490 10 286 0.81 (0.32-2.04)
Total 1,554 36 235
High risk polyps only 0 2,223 52 231 1 (Referent) 0.0098
1 1,631 24 187 0.59 (0.36-0.98)
≥2 1,620 14 173 0.40 (0.21-0.77)
Total 5,474 90 207
Poor quality exam & high risk 0 772 36 484 1 (Referent) 0.0084
1 484 13 270 0.44 (0.23-0.86)
≥2 581 11 258 0.34 (0.15-0.76)
Total 1,837 60 363
Atkin et al., Lancet Oncology Published online April 27,2017
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Cumulative CRC incidence after baseline
Atkin et al., Lancet Oncology Published online April 27,2017
Whole Intermediate Cohort Stratified by Subgroup
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Cumulative CRC incidence and SIRs after baseline and first surveillance
nTotal CRC cases
Cumulative incidence at 10 years
No. of CRCs
expected
Standardised incidence ratio (SIR) (95% CI)
After baseline (no surveillance)
Whole cohort 11,944 121 2.7% 111 1.09 (0.91-1.30)
Lower-risk subgroup 3,079 15 1.1% 29 0.51 (0.29-0.84)
Higher-risk subgroup 8,865 106 3.3% 82 1.30 (1.06-1.57)
p<0.0001*
After one surveillance onlyWhole cohort 6,925 51 2.3% 64 0.80 (0.59-1.05)
Lower-risk subgroup 1,668 6 0.7% 14 0.42 (0.16-0.92)
Higher-risk subgroup 5,257 45 2.8% 50 0.90 (0.66-1.21)
p=0.0431*
Atkin et al., Lancet Oncology Published online April 27,2017
* p-value from log-rank test comparing incidence in higher-risk vs lower-risk subgroup.
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