New York Society for Gastrointestinal Endoscopy

The 39th Annual New York Course Issues in Colorectal Cancer Screening

Sidney J. Winawer, MD, Fellow NYSGE

Memorial Sloan Kettering Cancer Center

New York, NY

NYSGE 1976 Yale Club

The New York Society

For Gastrointestinal Endoscopy

Presents:

A Day In

The Colon

Colonoscopy, Indications, Contraindications, Limitations

Co-sponsor: American Society for Gastrointestinal Endoscopy

Supported in part by grant from The American Cancer Society

1976 MSKCC

Colorectal Cancer in U.S. (1975–2011)

46% mortality reduction

Attributed primarily to screening

Report to Nation. Edwards, Cancer 2010; Kohler, JNCI 2015

New USPSTF Guidelines – 2015

CRC screening – Grade A

Tests not graded

Recommended tests

Colonoscopy q 10 yrs

FOBT q 1 yr

FS / FIT q 10 yrs / q 1 yr

Alternatives

sDNA q 3 yrs

CTC q 5 yrs

Issues in Colorectal Cancer Screening

Screening CO interval

Effectiveness of Screening CO

Interval Cancers

CO vs. FOBT

sDNA, blood tests

Single vs. multiple options

Disparities

Medico-Legal

Other

Screening Colonoscopy

1997 Guidelines: CO q 10 yrs

Adenoma – Carcinoma Sequence

Selby, NEJM 1992 – 10-yr protection from SIG

Colonoscopy Intervention – NPS

Winawer et al. Gastro 1997.

Effectiveness of Screening

Colonoscopy

Est. Incid. 67% − 77%

Est. Mortality 65%

Prox. / Distal Incid. 56% / 84%

Brenner, Ann Int Med 2011

Singh, JAMA / Gastro 2010

Kahi, Rex, Clin Gastro Hep 2009

Lakoff, Clin Gastro Hep 2008

Brenner, GUT, 2006

Impact of Screening Colonoscopy on Colorectal

Cancer Incidence and Mortality

RCT’s

Nordic/European Trial *

CO vs Usual Care

Spanish Trial

CO vs FIT

U.S. Trials (2)

CO vs FIT / gFOBT

Bretthauer et al., NEJM 2011

Quintero, Castells, et al., NEJM 2012

*Biostatistics – A. Zauber

*Scientific Support – IDCA: Winawer, Classen Co-Chairs

WEO Working Party

S. Winawer, A. Zauber

Interval Cancers

Normal Screening Colonoscopy 1/1000

Post Polypectomy 1/200

Kaminski. NEJM 2010

Robertson. GUT 2013

Reasons for Interval Cancers (Pooled data from 8 centers; 9,167 patients;

Mean follow-up: 47 months)

Missed Cancers 52%

Incomplete Polypectomy 19%

New Cancers 24%

Robertson: Gastro 2008 (A), Paper submitted

71%

Serrated Polyp Pathway CpG Island Methylation (CIMP)

BRAF, MSI

Non-

dysplastic

Serrated

Polyp

Lieberman, Rex, Winawer et al., Gastroenterology 2012

Legget, Gastroenterology 2010

Huang, Am Jn Gastroenterology 2004

Modified from D. Rex

Large

Hyperplastic

Polyp

Dysplastic

Serrated

Polyp

Serrated

Carcinoma

Serrated Polyp Identified

on Colonoscopy

Serrated Polyps 10%

Large (>1cm) or Dysplastic Serrated Polyps 1−3%

Risk of Synchronous AA/CRC 3−5X

Risk of Metachronous AA/CRC 3X

Proximal

Flat

Hiraoka. Gastro 2010

Schoen. Gastro 2010

Li. AJG 2009

Lee. Digestion 2008

Advances in Colonoscopy

High-resolution-magnification endoscopy

Autofluorescence (optical biopsy with laser fiber)

Spectral modulation: narrow band imaging, i-scan

Confocal laser endomicroscopy

Endosonography and targeted tissue sampling

Modified from G. Tytgat

Interval Cancers ADR and CRC Risk and CRC Deaths

Screening Colonoscopy Study

314.872 Colonoscopies

136 Gastroenterologists

Interval CRC’s

Advanced Stage CRC

CRC Deaths

Corley. NEJM 2014

Inversely

Associated

with ADR

Screening Issues

gFOBT / FIT CO

Main Effect Early Detection Prevention

Adv ADN sens 16 − 38% 88 − 94%

Screening adherence 48 − 60% (annual / decade) (single exam)

Dx w/u adherence 80% − 96% N /A

Initial cost Low (C/E) Higher (C/E)

Complications Low (single round) Low (screening)

Cai, Ca Prev Res 2011

Khaled-de Bakker, Ca Prev Res 2011

Murff, Ann Int Med 2010

Morikama, Gastro 2005

Hol, Gut 2010

Van Rossum, Gastro 2008

Van Roon, Gut 2012

Grotta, Clin Gastro Hep 2012

Pickhardt, NEJM 2003

Brenner, Ann Int Med 2011

Brenner, Gastro 2010

Kahi, Gastro Hep 2009

Imperiale, NEJM, 2008

Rex, Gastro 1997

Effectiveness as a Function

of Adherence to FIT: Age 50-75 LY

G p

er

10

00

FIT

Percent Adherence

Zauber, et al. Ann Int Med 2008

100 80 50

250

0

50

100

150

200

Colorectal Cancer Screening Strategies

Population

Colonoscopy

I

Colonoscopy

II

gFOBT / FIT

Stool DNA

Flex. Sig.

CTC

NCS

Bio-repository

“Menu” vs. Single Test

Recommendation

↑ Participation from choice

vs.

↓ Participation from confusion

Segnan JNCI 2005 Senore Gut 2013 Inadomi Arch Int Med 2012

Jones CEBP 2010 Redetmeler JAMA 1995

Elimination of Screening Colonoscopy Disparities NYC Coalition (C5)

Richards, Kerker, Thorpe, Olson, Krauskopf, Weber, Winawer, Am.Jn.Gastroenterology., 2011

Scre

en

ing

Co

lon

osco

py R

ate

Interval CRC Litigation

Procedure

Informed Consent

Complete CO — Ce / TI / Retroflexion

Adequate Prep

Photodocumentation

Biology

Proximal Location

Serrated / Flat CRC

FH

IHC

Other Issues in Surveillance

U.S. Multi-Society Task Force

Stopping Age? No! (USPSTF Stop? @75; Stop! @85)

Individualized based on assessment of benefit, risk,

co-morbidities . . .

Poor Prep? (Inadequate, suboptimal, fair) Repeat within a year

+ FOBT (Avoid!) after colonoscopy? Repeat colonoscopy

New significant rectal bleeding after colonoscopy? Re-evaluate for repeat colonoscopy

Lifestyle factors: race, gender, ethnicity? No change in surveillance

Lieberman. Gastro 2012

‘Wrap-Up’

Colorectal Cancer Mortality ↓

Primarily from screening

65% men + women screened in U.S.

80% by 2018 campaign launched

Effectiveness depends on high quality

colonoscopy and complete polypectomy

Many screening tests available

*NCCRT / CDC / GISoc.

THE BEST SCREENING TEST

IS

THE ONE THAT GETS DONE.