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Colonoscopy Surveillance Guidelines

David Lieberman MD

Chief, Division of Gastroenterology and Hepatology

Oregon Health and Science University

ACG Postgraduate Course October 13, 2013

What about Surveillance?

• Evidence – Patients with neoplasia “have what it takes” to do

it again

– Some low-risk, some high-risk

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Why Surveillance?

• Fear

–Missed Lesions

– Interval cancer after complete colonoscopy

GI endoscopist

Interval Cancer: What is the risk?

Cooper et al; Gastroenterol 2010: 138: S24 Singh, Am J Gastroenterol 28 Sept 2010 on line Baxter et al; Gastroenterol 2011; 140: 65-72

Pabby, GIE 2005; 61: 385-91 Alberts; NEJM 2000 342: 1156-62 Robertson; Gastroenterol 2005;129:34-41 Bertagnolli; NEJM 2006;355:873-84 Arber; NEJM 2006; 355:885-95 Baron; Gastroenterol 2006; 131:1674-82 Lieberman; Gastroenterol 2007; 133: 1077-85

After Polypectomy

Incidence: 0.3-0.9% in 3-5 yrs

1.7-2.8 cancers /1000 person yrs

After (-) Colonoscopy

2-9% of ALL cancers

(within 6-36 months)

Arain; Am J Gastroenterol 2010; 105: 1189-95

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Interval CRC

?? Biology ??Quality

Interval Cancer: WHY? • New, fast growing lesions – Biology

• 1323 CRC in registry;

– 63 interval CRC* (4.8%)

– 131 matched non-interval CRC

Proximal Colon CIMP MSI

Interval CRC (n=63) 63% 57% 29%

Non-interval CRC (131)

39% 33% 11%

OR for Interval CRC

1.85 (1.01-3.8) 2.41 (1.2-4.9) 2.7 (1.1-6.8)

Arain; Am J Gastroenterol 2010; 105: 1189-95

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Interval Cancer

• Molecular analysis

– 62 cancers diagnosed within 5 years after colonoscopy with molecular data

• CIMP (+): OR 2.19 (1.14-4.21)

• MSI-H: OR 2.10 (1.10-4.02)

• Increased methylation level

Nishihara et al; NEJM 2013; 369:1095-1105

Sessile Serrated polyp

Serrated Polyps

• Pathway may account for up to 20% of CRC

• Genetic pathways are partially characterized

Leggett and Whitehall; Gastro 2010;138: 2088-2100

Proximal Normal function:

Induces senesence

CpG island

Methylation: Sessile

Serrated

Polyp Silence MLH1

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Interval Cancer: WHY? • New, fast growing lesions

• Incomplete removal (19-27%) – Pabby et al; Gastrointest Endosc 2005; 61: 385-91

Soetikno;JAMA 2008; 299: 1027-35 Farrar; CGH 2006; 4: 1259-64

Chromoendoscopy for flat lesions

Incomplete Removal of Polyps

• Prospective study

– 346 non-pedunculated adenomas removed by 11 Gis

– After “complete” removal, bx obtained on periphery to calculate “incomplete resection rate” (IRR)

IRR Real Rate

All 10.1% ???

5-9mmm 6.8% ???

10-20mm 17.3% ???

Sessile serrated 31.0% ???

Range among endoscopists

6.5-22.7% ???

Pohl; Gastroenterology 2013;

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Interval Cancer: WHY? • New, fast growing lesions

• Incomplete removal (19-27%)

• Missed lesions

– Up to 17% of polyps > 1cm are missed !!

– Less protection in proximal colon

Interval Cancer

• 9167 participants from 8 large colonoscopy studies

• Median follow-up of 4 years

• 58 invasive cancers found during surveillance (0.63%)

• 78% were stage I or II

Robertson et al. DDW 2008 Abstract 795

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Tadepalli et al; GIE 2011; 74: 1360-8

Serrated Polyps – We miss them !

• N = 158

• Endoscopic Characteristics:

Characteristic %

Mucous cap 63.9%

Rim of debris/bubbles 51.9%

Alteration of contour of fold 37.3%

Interruption of mucosal vascular pattern

32.3%

Tadepalli et al; GIE 2011; 74: 1360-8

Hepatic flexure 1.5 cm -Very flat, red coloration -Slight mucus

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Serrated Polyp Detection

• Variation in detection of proximal serrated polyps

Study # endoscopists Rate of detecting >1 proximal serrated polyp

Kahi; CGH 2011; 9: 42

15 1% to 18%

Wijkerslooth DDW 2012

5 6% to 22% Huge Variation !!!

Interval CRC

Biology

+ Quality

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Colon Surveillance Utilization Age and Gender

< 50 50-74 >74

Female Male Female Male Female Male

Polyp/CRC Surv

6.5% 8.6% 16.6% 23.7% 28.2% 37.1%

CORI Database 2000-2011 n = 1,348,140

>25% of all colonoscopies for age >55 yrs

Surveillance after polypectomy:

Baseline: Most advanced finding* Recommended Interval

No polyp 10 yrs

Hyperplastic, left-sided 10 yrs

1-2 Tubular Adenomas <10mm 5-10 yrs

Lieberman et al; Gastroenterology 2012; 143: 844-857

Low Risk

*Assumes complete exam with adequate prep

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No Polyp at Baseline CSP

• Evidence for 10 year interval

– Data demonstrating 10+ year gaps in adenoma development and cancer

– RCT of sigmoidoscopy in UK

– Case-control studies of sigmoidoscopy and colonoscopy

• Concern: Interval cancer after negative exam

– 2-9% of CRC patients in registries had prior colonoscopy within 3 yrs

• Recommended Interval: 10 years

No polyp at baseline: Risk of Interval Advanced Neoplasia

Study n Age (yrs) Advanced Neoplasia @5 yrs

Lieberman, 2007 291 (USA men) 62 2.4%

Imperiale, 2008 1256 (USA) 56.6 1.3%

Leung, 2009 370 (Chinese) 60.6 1.4%

Chung, 2011 1242 (Korean) 56.7 2.0%

Risk is low

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Risk of CRC within 10 yrs after Colonoscopy

Study Country (n) Cancer risk over 10 yrs

Singh JAMA 2006

Manitoba 36,000 with CSP c/w expected rates

SIR 1 yr 0.66 2 yr 0.59 5 yr 0.55 10 yr 0.28

Brenner J Clin Onc 2011

Germany 1945 CRC cases 2399 controls

OR 1-2 yr 0.14 3-4 yr 0.12 5-9 yr 0.26 10-19 yr 0.28

Normal colonoscopy identifies low-risk person

CRC Incidence

Nishihara et al; NEJM 2013; 369:1095-1105

No CSP >15.1 10.1-15.0 10.0-5.1 5.0-3.1 <3.0

Person years

980,154 1668 10,929 54,601 99,783 131,333

CRC cases 1164 3 8 51 70 77

Hazard ratio

0.65 (0.19-2.23)

0.26 (0.12-0.59)

0.52 (0.38-0.70

0.40 (0.31-0.52)

0.35 (0.28-0.45

Years since last negative colonoscopy

Negative colonoscopy associated with reduced risk for 15 years

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Overuse of Screening After a Negative Colonoscopy in the Elderly (Medicare)

Goodwin JS et al. Arch Intern Med 2011;171:1335-43

(-)Colonoscopy for screening indication

(-) colonoscopy (all indications)

% repeat CSP 50% 30%

4yr 5yr 6yr

Utilization of Colon Surveillance

Schoen et al; Gastroenterol 2010; 138: 73-81

Surveillance in 5 yrs >2 Surveillance in 7 yrs

Advanced Adenoma (n = 1342)

58.4% 33.2%

> 3 non-advanced adenomas (n = 177)

57.5% 26.9%

1-2 non-advanced adenomas (n = 905)

46.7% 18.2%

No adenomas 26.5% 10.4%

Evidence for over-utilization

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Surveillance after polypectomy:

Baseline: Most advanced finding* Recommended Interval

No polyp 10 yrs

Hyperplastic, left-sided 10 yrs

1-2 Tubular Adenomas <10mm 5-10 yrs

Lieberman et al; Gastroenterology 2012; 143: 844-857

Low Risk

*Assumes complete exam with adequate prep

Tubular adenoma <10mm

• New Evidence

– Low-risk compared to:

• 3 or more

• Advanced histology

– Compared to No polyps at baseline 5-year risk of advanced neoplasia:

Study No polyp 1-2 Tub Ad RR

Lieberman,2007 2.4% 4.6% NS:1.92 (0.83-4.42)

Pinsky, 2008 5.3% 5.3% NS

Chung, 2011 2.0% 2.4% NS:1.14 (0.61-2.17)

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Tubular adenoma <10mm

• Recommendation: 5-10 yrs

– Evidence leaning toward longer interval for most

Utilization of Colon Surveillance

Schoen et al; Gastroenterol 2010; 138: 73-81

Surveillance in 5 yrs >2 Surveillance in 7 yrs

Advanced Adenoma (n = 1342)

58.4% 33.2%

> 3 non-advanced adenomas (n = 177)

57.5% 26.9%

1-2 non-advanced adenomas (n = 905)

46.7% 18.2%

No adenomas 26.5% 10.4%

Evidence for both over-utilization and under-utilization

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Surveillance after polypectomy:

Baseline: Most advanced finding* Recommended Interval

No polyp 10 yrs

Hyperplastic, left-sided 10 yrs

1-2 Tubular Adenomas <10mm 5-10 yrs

3 or more tubular adenomas 3 yrs

Tubular adenoma >10mm 3 yrs

Villous adenoma (>25% villous) 3 yrs

Adenoma with HGD 3 yrs

>10 adenomas <3 yrs

Piecemeal resection 2-6 months

Cancer 1 year

Lieberman et al; Gastroenterology 2012; 143: 844-857

Low Risk

Higher Risk Stronger evidence

*Assumes complete exam with adequate prep

Cancer

• Consensus recommended interval for surveillance: 1 year after cancer resection

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Serrated Polyps: Significance?

• At Screening Colonoscopy: Association with synchronous advanced neoplasia at screening colonoscopy

• At Surveillance: May be associated with increased risk of advanced neoplasia in surveillance

Li et al; Am J Gastroenterol 2009; 104: 695-702 Schreiner, Weiss, Lieberman; Gastroenterol 2010; 139: 1497-1502 Hiraoka et al; Gastroenterol 2010; 139: 1503-10

Serrated Polyps (SP): What should we do?

Risk Level Suggested Surveillance

High Hyperplastic polyposis (>5 SSA proximal to sigmoid with 2 >10mm)

Moderate Serrated polyp with dysplasia Serrated polyp >10mm

Low SP without dysplasia in proximal colon

Very low Classic hyperplastic polyps

Terdiman, McQuaid; Gastro 2010; 139: 1444-7

1 year

3 years (similar to HRA)

5 years or more (similar to LRA)

10 years

Lieberman et al; Gastroenterology 2012; 143: 844-857

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Surveillance Program: What to do after 1st surveillance?

Baseline CSP 1st Surv. Pinsky 2009 PLCO

Laiyema, 2009; PPT

Robertson 2009

HRA* HRA 19.3% 30.6% 18.2%

LRA 6.7% 8.9% 13.6%

No adenoma 5.9% 4.8% 12.3%

LRA HRA 15.6% 6.9% 20.0%

LRA 5.7% 4.7% 9.5%

No adenoma 3.9% 2.8% 4.9%

No Adenoma HRA 11.5%

LRA 4.7%

` No adenoma 3.1%

Advanced Neoplasia at 2nd Surveillance

*High-risk adenoma (HDA): Adenoma >10mm, villous, HGD

Surveillance Program

• Follow-up of patients after they undergo surveillance is uncertain

• Patients with HRA* at any exam are higher risk

Baseline CSP 1st Surveillance Interval for 2nd surveillance (years)

LRA HRA 3

LRA 5

No adenoma 10

HRA HRA 3

LRA 5

No adenoma 5

* adenoma >10mm, villous, HGD

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Other surveillance issues

• Poor prep at baseline

– Lebwohl (Gastrointest Endosc 2011;73: 1207-14)

• 24% with suboptimal bowel prep

• Repeat exams: – Any adenoma 42%

– Advance adenoma 27%

– Recommendation: Repeat exam

Other surveillance issues

• Positive interval FOBT or FIT

– Interval test within 5 years of colonoscopy is NOT recommended

– Management decision should be individualized

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USA vs UK Guidelines Risk Level Follow-up

Recommendation

USA Lower risk: 1-2 tub adenoma <10mm with LGD

5-10 yrs

Higher risk: 3-10 adenomas or >10mm or Villous/HGD

3 years

Highest risk: >10 adenomas

<3 yrs

UK Low-risk: 1-2 adenomas <10mm

No surveillance or 5 yrs

Villous/HGD Histology not used

Intermediate risk: 3-4 adenomas <10mm or on >10mm

3 yrs

High-risk: >5 small or >3 with one >10mm

1 year

USA vs UK

• NCI-funded analysis of 4 US prospective studies

– Interventional studies (anti-oxidant, Calcium, diet)

– Inclusion: adenoma-bearing patients

– Endpoint: adenoma recurrence at 3 yrs

– Clearing colonoscopy performed at 1 yr to assure all baseline polyps removed

– Era: 1984-1998

Martinez; Ann Intern Med 2012; 157: 856-64

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USA vs UK

Martinez; Ann Intern Med 2012; 157: 856-64

Risk Group n Adv neoplasia @ 1yr

Risk HGD/CRC @ 1 yr

Absolute Risk

USA

Low-risk 1194 (37%) 45 3.8% 3 0.3%

Higher-risk 2028 (62.9%) 227 11.2% 23 1.1%

Highest risk 4 1 0

UK

Low-risk 1460 (45.3%) 64 4.4% 5 0.3%

Intermediate 1375 (42.6%) 136 9.9% 13 0.9%

High-risk 391 (12.1%) 73 18.7% 8 (6 CRC) 2.0% (0.6-3.5)

USA vs UK – Lessons learned

• Likely that all important lesions at one year were missed at baseline – This is the reason for the 1 year exams in these

studies

• Quality of baseline exam is important – If there is any question about quality in patients

with 5 or more adenomas, exam should be repeated

– Further study is needed to determine if repeat exams are needed when high-quality is assured

Martinez; Ann Intern Med 2012; 157: 856-64

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Polyp Surveillance: Summary

• Emphasis should be on performance of high-quality baseline colonoscopy

• Intervals for surveillance should adhere to evidence-based guidelines – If early surveillance is recommended,

a reason for deviating from the guideline should be documented

• New information on surveillance programs suggest that many patients can have longer intervals after 1st surveillance