Falk SymposiumOctober 1, 2005

Impact of National Polyp Study

Sidney J. Winawer, M.D.Memorial Sloan-Kettering Cancer Center

New York, NY

Diagnosis of Large Bowel Cancerin Asymptomatic Patients

Screening of Asx, PeopleIntermittent BleedingDietary ControlGuaiac Cards

David H. Greegor, MDColumbus, Ohio

JAMA Sept. 18, 1967

Hirschowitz, 1950s

Colonoscopyc. 1970

Adenomatous Polyp

Shinya & Wolf, 1976

Adenoma Burden from Screening

Adenomas Cancers

Flex Sigmoidoscopy 12% 0.3%

FOBT Pos. Pts. 27% 3%

Colonoscopy 18–36% 1%

Mandel, NEJM 1993; Atkin, Lancet 2002; Lieberman, NEJM, 2000.

Post-Polypectomy Surveillance1970s

Common Practice:Annual Follow-up Colonoscopy

Cori Data. Lieberman

Colonoscopy workloadabout 25% surveillance inpeople over 50 yrs. of age

National Polyp Study

Randomized Trial

Surveillance Intervals

Surveillance Methods

CRC Incidence

Adenoma-Carcinoma Model

7 Clinical Centers

MSK Coord. Center

1980

Colorectal Cancer Incidence in NPS Following Colonoscopic Polypectomy

(1418 pts; 8401 person yrs)

Winawer, Zauber et al. 1993. NEJM 329:1977-81

National Polyp StudyAdvanced Adenomas at Follow-Up

3%

32%

R

3%

1 year 3 year

Winawer, Zauber et al. NEJM 1993.

U.S. Colorectal Cancer Screening Guidelines

Consensus

U.S. Preventive Services Task Force 1996

GI Consortium 1997

American Cancer Society 1997

SCREENING GUIDELINES

Screening Colonoscopy q 10 Yearsfor Average Risk Men and Women

Colorectal cancer screening clinical guidelines and rationale. Winawer, Fletcher, et al., GE, 1997ACS colorectal screening guidelines. Byers, Levin et al., CA, 1997

NPSColonoscopy/Barium Enema

ComparisonBlinded/Unblinded Method

Comparison of DCBE & Colonoscopy*

862 Paired Exams in 580 Pts.

DCBE Detection 48% for Adenomas >1 cm

*Winawer, Zauber et al, NEJM 2000

Virtual Colonoscopy

Pickhardt et al. NEJM 2003

Cohort: 1223 Asx

Designs: Blinded V.C. vs. Co.

V.C. vs. Co.: Equivalent

V.C. Sensitivity: 94% for Adenomas ≥ 8 mm

Method: Initial 3D, Electronic Cleansing

1380-4*Zauber, Winawer et al, GE 1997

Post-Polypectomy SurveillancePo

lype

ctom

y IncreasedRisk

LowerRisk

30%

70%3 yr

5 yr

New GuidelinesProcess

U.S. Multisociety Colorectal Cancer Task Force

American Cancer Society

Systematic Literature Search

Predictors of Advanced Adenomas

Risk Stratification

Advanced Adenomas: >1 cm or villous featuresor high grade dysplasia

US Multisociety Taskforce & ACS, 2005

Predictors of Riskfor Advanced Adenomas

US Multisociety Taskforce & ACS, 2005

Multiplicity (> 3 Adn)Size (> 1 cm)Villous FeaturesHGD

Increased Risk

1 or 2 adenomasSize (< 1 cm)No Villous FeaturesNo HGD

Lower Risk

Recommendations forFollow-up Colonoscopy

3–10 adenomas, or anyadvanced adenoma 3 yrs>10 adenomas < 3 yrsPiecemeal or incomplete 2–6 monthsHNPCC Intensive F/U (1–2 yrs)

Increased Risk

1 or 2

Colonoscopy Miss Rateof Adenomas

AdvancedAdenomas Adenomas

Rex* 24% 6%

Hixson** 15% 0%

*GE 1997**JNCI 1990

Colonoscopy Miss Ratesfor CRC

Bressler GI 2004 4%Rex GE 1997 5%

3% for Gastroenterologists13% for non-Gastroenterologists

Reasons for Interval Neoplasia

Inadequate Bowel Prep

Fast Withdrawal Time

Piecemeal Removal of Large Sessile Polyps

Fast Track Cancers — MMR Pathway (15–20%)

US Multisociety TaskForce Rex et al Am J. GE 2002.Barclay et al GIE 2005.

FOBT in Post-Polypectomy Patients Under Colonoscopy

Surveillance

No. Patients 1,305No. with + FOBT 132No. with Adv. Adn. 17 (23%)No. with Unnecessary 115 (77%)

Colonscopy

Zauber, Winawer et al, GE 2002

Additional Recommendations

Clear recommendation by endoscopist to PCP

No interval FOBT

Discontinue surveillance with comorbidities

Diagnostic Colonoscopy for interval symptoms

Evolving technology not established for these patients

US Multisociety Taskforce & ACS, 2005

Proceedings of the Royal Society of Medicine

1977

The Polyp-Cancer Sequence

Basil Morson, M.D. St. Marks Hospital London, UK

NPS & Erasmus Medical Center Collaboration

NPS Data

MISCAN-MODEL

Evidence for Adenoma Regression

Dynamic Adenoma-Carcinoma Sequence

Implications for Chemoprevention and Nutrition Trials

Loeve, Zauber, Winawer, et al., JNCI 2004.

National Polyp StudyFlat Adenoma

FlatAdenomas

Matsui et al.,World J Surg2000.

Aggressive pathology

National Polyp StudyAdenoma Shape and High Grade Dysplasia

1.3%(6/474)

10.0%(80/802)

7.4%(17/229)

0 2 4 6 8 10 12

Flat

Sessile

Pedcl

P = .0001

10.0% (80/802)

7.4% (17/229)

1.3% (6/474)

Pedunculated

**1/3 of NPS adenomas classified as flat pathologically

O’Brien, Winawer, Zauber et al, Clin GE & Hep, 2004

National Polyp Study

Relative Risk for Advanced Adenomasat Follow-Up

*Adjusted for adenoma multiplicity and age/family history

• 938 pts — mean 5.9 yrs FU

• 42 pts — developed Advanced Adenomas

• 0.76RR — advanced adenomas in pts with Flat Adenomas relative to No Flat Adenomas*

O’Brien, Winawer, Zauber et al, Clin GE & Hep, 2004

SummaryImpact of NPS

Randomized Surveillance GuidelinesRisk Stratification GuidelinesPolypectomy Reduces CRC IncidenceScreening ColonoscopyModel for Chemoprevention/Nutrition TrialsModel for Blinded/Unblinded Comparison of colonoscopy and colonography – DCBE/CoDynamic Adenoma Carcinoma Sequence

Additional NPS Studies

Hyperplastic PolypSerrated AdenomaMortality F/U

NPS 1980