barrett’s esophagus: ablate everyone? - american...

Nicholas Shaheen, MD, MPH, FACG

Barrett’s Esophagus:Ablate Everyone?

Nicholas Shaheen, MD, MPH, FACGCenter for Esophageal Diseases and Swallowing

University of North Carolina

Greetings from UNC, the University of National Champions!

• Men’s Basketball: ’24, ’57, ’82, ’93, ’05, ‘09

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• Men’s Soccer: ’01, ‘11• Women’s Basketball: ’94• Men’s Lacrosse: ’81, ’82, ’86, ’91, ‘16• Field Hockey: ’89, ’95, ’96, ’97, ’07, ’09• Women’s Lacrosse: ’13, ‘16

ACG 2016 Annual Postgraduate Course Copyright 2016 American College of Gastroenterology

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The Conceptual Underpinnings for

Endoscopic Therapy in Barrett’s Esophagus

Adenocarcinoma – A Disease with a Rapidly Increasing Incidence

S Kroep et al. Am J Gastroenterol 2014.


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It is not going to change any time soon…

Kong CY et al, CEBP, 2014.

It is clear that the status quo is failing.


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The Case for Ablation in HGD

• The risk of progression of the lesion is high• The risk of a metachronous cancer is substantial• The competing strategy (surgery) is morbid• Patients are often more comfortable with a

proactive strategy• Data suggest a decreased cancer risk

RFA

RCT of 127 Subjects with LGD & HGD• Intervention: RFA+PPI or Sham+PPI (2:1)• Follow-up: 12 mos• Assessment: Bx’s q3 mos (HGD)/ 6 mos

(LGD)• 1° Outcomes:

• Ablation of all dysplasia:• 81% of HGD• 91% of LGD• app 20% of controls

• Complete eradication of IM (77% of Rx, 2% Sham)

• SE’s: Strictures in 6% of subjects

05

1015202530

CancerIncidence (%)

Sham+PPIRFA +PPI

Shaheen NJ et al. N Engl J Med, 2009.

The AIM-D Trial

19%

2%


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Complete Eradication, US RFA Registry

AIM-D at 5 Years

0.0

00

.25

0.5

00

.75

1.0

0IM

-fre

e p

rop

ortio

n

0 500 1000 1500 2000Days since first CEIM at 12 months or after

LGD HGD

Kaplan-Meier analysis of the durability of CEIM

0.0

00

.25

0.5

00

.75

1.0

0D

ysp

lasi

a-fr

ee p

rop

ortio

n

0 500 1000 1500 2000Days since first CED at 12 months or after

LGD HGD

Kaplan-Meier analysis of the durability of CED

Shaheen et al. DDW 2015


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Recurrence Rates by Baseline Histology, U.S. RFA Registry

0.00

0.25

0.50

0.75

1.00

0 1 2 3Time after CEIM (years)

Nondysplastic BE Indefinite dysplasiaLGD HGDIMC

If Someone Recurs, What Do They “Come Back” As?

Pre

-T

reat

men

t H

isto

logy

IM Recurrence Histology

Recurrencen (%)

NDBEn (%)

INDn (%)

LGDn (%)

HGDn (%)

IMCn (%)

EACn (%)

All Patients (N=1634) 334(20) 269 (81) 18 (5) 19 (6) 15 (4) 13 (4) 0

NDBE (N=668) 119 (18) 110 (92) 4 (3) 3 (3) 2 (2) -- --

Indefinite Dysplasia (N=114) 25 (22) 21 (84) 2 (8) 1 (4) 1 (4) -- --

LGD(N=323) 70 (22) 57 (81) 6 (9) 4 (6) 1 (1) 2 (3) --

HGD(N=416) 93 (22) 64 (69) 4 (4) 10 (11) 9 (10) 6 (6) --

IMC(N=92) 21 (23) 16 (76) -- -- 1 (5) 4 (19) --

EAC(N=21) 6 (29) 1 (17) 2 (33) 1 (17) 1 (17) 1 (17) --


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Most Recurrences Are Handled Endoscopically

Phoa KN et al. Gastroenterology 2013.

Complications with RFA

5,516 Patients

15,665 FAs

Complications: 283

Per Patient: 5.4%

Per RFA: 1.8%

Strictures: 233Per Patient: 4.5%

Per RFA: 1.5%

Bleeding: 28Per Patient: 0.5%

Per RFA: 0.2%

Hospitalization: 47Per Patient: 0.9%

Per RFA: 0.3%

Perforation: 2Per Patient: 0.04%

Per RFA: 0.01%

Deaths:0

Wolf A et al. DDW 2014.


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What are Cancer Rates after RFA?

Baseline Histology

No. of Patients

n (%)

Patient Years of

Follow-up

No. Incident

EAC

EAC Incidence Rate per 1000 person-years

[95% CI]

No. Deaths from EAC

EAC Mortality Rate per 1000 person-years

[95% CI]

NDBE 2,473 (48) 5,691 3 0.5[0.1, 1.4]

0 0

IND 385 (8) 883 2 2.3[0.4, 7.5]

0 0

LGD 1049 (21) 2,563 14 5.5 [3.1, 8.9]

0 0

HGD 972 (19) 2,591 81 31.3[25.0, 38.7]

3 1.15 [0.29, 3.15]

Total, non-malignant

4,879 (95) 11,729 100 8.5 [7.0, 10.3]

3 0.26 [0.07, 0.70]

IMC 178 (4) 459 -- -- 1 2.18 [0.11, 10.7]

IAC 60 (1) 155 -- -- 0 0Total 5,117 (100) 12,343 -- -- 4 0.32

[0.10, 0.78]

Wolf WA et al, Gastroenterology 2015.

So Ablative Therapy WorksBut Does Everyone Need It?


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The Decision for Endoscopic Therapy – When to Intervene?

Favors Surveillance Favors Endoscopic Therapy

COST



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COST

RISK


COST

RISKCHANCE OF

INTERVENTION LATER



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COST

RISKCHANCE OF

INTERVENTION LATER

LEVEL IEVIDENCE


COST

RISKCHANCE OF

INTERVENTION LATER

LEVEL I EVIDENCE

PEACE OF MIND



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What is Rate of Progression of LGD?

Hvid-Jensen F et al. N Engl J Med 2011.

How Benign is Low-Grade Dysplasia?

• 147 subjects with a diagnosis of LGD made in a community practice in the Netherlands

• Path reviewed by 2 expert pathologists• Disagreements resolved by consensus

• 85% of cases were down-graded• In the 15% who were not, the incidence rate of

HGD or EAC was 13.4%/pt-yr (mean f/u: 51 months)

Curvers WL et al. Am J Gastroenterol 2010.


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Is LGD an Indication for Endoscopic Intervention?SURF study

RCT, n=140, surveillance EGD vs. ablation with RFA• Primary outcome: occurrence of HGD/EAC

Phoa KN et al. JAMA 2014

Is Non-Dysplastic BE an Indication for Ablation?

• Is it effective?• Most studies document high rates of reversion to squamous tissue• Data from U.S. RFA Registry shows a markedly decreased rate of cancer

in NDBE after RFA compared to historical controls (0.5/1000 p-y)

• Can we afford it?• Cost-effectiveness is questionable• Will treat 20 or more for one to benefit• Effective intervention is still available if they progress to dysplasia

• Bottom line: Until better risk stratification is available, highly unlikely we will be recommending RFA for all NDBE


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An Algorithm for Endoscopic Management of Barrett’s

Neoplasia

Nodular Disease Should Be EMR’ed!

Ell C et al. GIE, 2007


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Algorithm, cont.

• For subjects with nodular disease, EMR histology decides further management

• No cancer, mucosal cancer, or maybe sm1 cancer -> ablative therapy

• Worse than sm1 -> consideration of multimodality Rx and esophagectomy

• Flat HGD -> ablation• Given current data, RFA seems most appropriate

Algorithm, cont.• LGD

• Unifocal, elderly, and/or wishing conservative Rx -> surveillance endo’s

• Multifocal, previously nodular, young, family hx of cancer, pathologically worried -> consider ablation

• Non-dysplastic• Ablation is an option, but role in average risk patients not

clear


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Unsettled Questions…

Should I Be Learning ESD?

• ESD is more technically challenging and time-consuming than EMR

• Asian endoscopists learn in the stomach and colon

• The only real data that ESD yields that EMR does not is lateral margin data

• Because depth of invasion is the most clinically actionable data from EMR, the lateral margin data are not essential

• Given the limited availability of training, the low utility of the incremental data, and the potential for greater complications, performing good EMR should be the focus for most Western endoscopists


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Does Case Volume Matter and How Much Do I Need?

p=0.01

2.1

2.2

2.3

2.4

2.5

2.6

0 50 100 150 200

Patients Previously Treated at CenterPredicted Value 95% CI

RFA

Ses

sions

based upon Center ExperiencePredicted RFA Sessions to Achieve CEIM

Pasricha et al, Gastroenterology 2015.

Rates of Recurrence after CEIM by Volume at USRFA Centers

Pasricha et al, Gastroenterology 2015.


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When Is Endoscopic Rx Inadequate?• Lesion too deep

• Anything SM1 or deeper deserves consideration of esophagectomy

• SM1 may be managed endoscopically if the patient is a poor surgical cancer

• Lesion too aggressive• Poor differentiation • Lymphovascular invasion

• Lesion not amenable to endoscopic Rx• Won’t raise, too large

Invasion depth and risk of LNM

500µm500µmmm

sm

lpep

m1 m2 m3 sm2 sm3

36 – 54%0-3%

1000µm1000µm

sm10 – 22%

??


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Conclusions• In 2016, superficial neoplasia, incl. mucosal esophageal

adenocarcinoma, is an endoscopic disease!• Non-dysplastic BE is generally too low risk to warrant ablation

• CAVEATS• Appropriately selected patient• Amenable lesion• Expertise and program in place• Patient appraised of risks and benefits of this approach

• Endoscopist must know when cure becomes less likely• Submucosal invasion is a contra-indication to endoscopic management in a good surgical

candidate

• Results are overall durable, but recurrent intervention is not uncommon

• Close communication, with no recrimination, between surgeon, oncologist and endoscopist is essential

• Endoscopists must learn to think like oncologists

Thanks!


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