Barrett s Esophagus: What to Do for No Dysplasia, LGD, and HGD?

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1 Barrett s Esophagus: What to Do for No Dysplasia, LGD, and HGD? Nicholas Shaheen, MD, MPH Center for Esophageal Diseases and Swallowing University of North Carolina 1 Outline What are the risks of progression in BE? What are the management options for ND, LGD & HGD? What data support efficacy of ablative therapy in non-dysplastic & dysplastic BE? What is an appropriate p algorithm to follow for endoscopic intervention in BE? 2 1

2 Barrett s Classification and Management Non-dysplastic IM Surveillance every y3y years Detect progression to dysplasia or cancer LGD (low-grade dysplasia) Surveillance every 6-12 months Detect progression to HGD or cancer HGD (high-grade dysplasia) Surveillance every 3 months Esophagectomy EMR and ablation: options at select institutions 3 Wang KK, Sampliner RE. Am J Gastroenterol Human Esophagus Ablation Target Muscularis mucosae (Ablation Target Depth) Submucosa with esophageal glands G G Controlling ablation depth avoids stricture EMR Depth Muscularis propria 4 Surgical Depth 2

3 Progression to Cancer in HGD Buttar et al N=100 32% Surveillance Period 8 Years Schnell et al N=77 16% 7.3 Years Reid et al N=76 59% 5 Years 0% 10% 20% 30% 40% 50% 60% 70% 5 Reid et al. Am J Gastro 2000;95: Schnell et al. Gastro 2001; 120: Buttar et al.gastro 2001;120: Medical Therapy All subjects should get PPI Super-therapeutic doses have not been shown more effective Routine ph monitoring not necessary Routine ASA not recommended Often indicated on basis of cardiac risk factors 6 3

4 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(meanf/u:51 months) Curvers WL et al. Am J Gastroenterol 2010, pub pend. 7 Is It Really Dysplastic? 100% 80% 60% 1.2% 3.9% 2.4% 72.3% 69.0% Cancer HGD LGD IND/ND-IM 40% 20% 24.1% 23.3% 0% LGD (n= 83) HGD (n= 129) Home Institution Diagnosis 3.9% 8 4

5 Isn t the Risk of Cancer too Low in LGD and ND to Justify Intervention? The risk of cancer in any single year is low for those with ND. The NNT to prevent one cancer in a given year may be >200. Wani S et al. GIE Consider a 40 yo male w/ ND-BE Such an individual may have yrs of life expectancy in 2010 If risks are linear, compounding 0.5% over this time yields an overall cancer risk of 20-25% Single year NNT s are irrelevant Ablation is illogical for someone with a short life expectancy The real questions are what the lifetime cancer risk for the individual is, and how much it could be lowered with ablation? 10 5

6 We Don t Have Good Data on the Longterm Protective Effect of Ablation But we can make some estimate of the effect of endoscopic ablation and compare it to natural history studies Risk from natural history studies: 6/1000 Risk from meta-analysis of ablation: 1.6/ Wani S et al. Am J Gastroenterol Using these data, let s play some hypotheticals Cancer Risk Natural History S/P Ablation 1/2 as Effective yr survival 10 yr survival 20 yr survival 40 yr survival 12 6

7 But It Depends on Baseline Risk! 30 Cancer Risk Natural History S/P Ablation 1/2 as Effective yr survival 10 yr survival 20 yr survival 40 yr survival 13 Ablation of Lesser Forms of Dysplasia Might be Effective and Cost-Effective LGD $20,000 $18,000 $16,000 $14,000 $12,000 Cost $10,000 $8,000 $6,000 $4,000 $2,000 $ QALYs no surveillance no surveillance after ablation ablation with surveillance surveillance 14 Inadomi JM et al. Gastroenterology

8 What is the Risk of Death with Esophagectomy? Day Mortality <2/yr 26/ 2-6/yr >6/yr Number of Esophagectomies/Year Birkmeyer et al, NEJM, If an Endoscopic Intervention is to be Pursued 16 8

9 Choose Your Weapon! Fiber Optic Guide Endoscope Spacing Balloon High-Grade Dysplasia Laser Light 17 AIM Dysplasia Trial U.S. multi-center, randomized, single- blind, sham-controlled clinical i l trial 18 N Engl J Med 2009;360(22):

10 AIM-Dysplasia Trial Study Design Randomized, sham-controlled design 2:1 RFA vssham Stratified by: degree of dysplasia (LGD vs. HGD) length of segment (1-4 cm vs 4-8 cm) Maximum of 4 RFA sessions Identical biopsy protocols, equal sampling 12 month cross-over 19 N Engl J Med 2009;360(22): Methods (cont.) Primary Outcomes (12 months) Complete eradication of fdysplasia all biopsy specimens free of dysplasia RFA vs. control, HGD and LGD analyzed separately Complete eradication of intestinal metaplasia all biopsy specimens free of IM RFA vs. control, all patients N Engl J Med 2009;360(22):

11 21 N Engl J Med 2009;360(22): N Engl J Med 2009;360(22):

12 Stricture Occurrence 5 Strictures in 84 patients 5 of 84 patients (6.0%) 5 of 298 cases (1.7%) All resolved, mean 2.6 dilations All achieved complete eradication of intestinal and dysplasia Results (cont.) 23 N Engl J Med 2009;360(22): What About the Risk of Buried Barrett s? 24 12

13 Results Buried Barrett s (SSIM) Histology: Sub-squamous Intestinal Metaplasia Baseline incidence of SSIM (25%) HGD cohort: 21% of patients LGD cohort: 30% of patients 12 month incidence of SSIM RFA cohort: 6.8% of patients Sham cohort: 60% of patients* *p<0.05 Fisher s exact test, RFA vs. Sham 25 N Engl J Med 2009;360(22): In this multi-center, randomized, shamcontrolled study of radiofrequency ablation in patients with dysplastic Barrett s esophagus, there was a high rate of complete eradication of dysplasia and intestinal metaplasia and decreased disease progression in the ablation group, as compared with the control group. 26 N Engl J Med 2009;360(22):

14 3 year Durability 27 Shaheen NJ et al, Gastroenterology, What are the True Risks with Ablation? Chest Pain Pretty much everyone gets some 23/100 on a VAS in recent RCT Resolves on average by a week or so Bleeding Perforation Stricture Buried BE 28 14

15 Systematic Review of Complications with RFA Frantz DF, Dellon ES, Shaheen NJ. Tech Gastrointest Endosc, Given the relatively short-term nature of data after ablation, it is unwise currently to cease surveillance endoscopy after ablative therapy

16 Evolving Technology in BE 31 Cryotherapy in HGD: An Initial Report 98 subjects w/ HGD treated at 10 institutions % w/ Eradication completed Rx, ongoing total procedures /pt 58 No perfs, no buried glands, 40 no bleeds or chest pain requiring hospitalization 20 One progression to CA 0 CR-HGD CR-D CR-IM 32 Shaheen NJ et al. Gastrointest Endosc,

17 Algorithm for Endoscopic Intervention in BE 33 Nodular Disease Should Be EMR ed! 34 Ell C et al. GIE,

18 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 35 LGD Algorithm, cont. Unifocal, elderly, and/or wishing conservative Rx -> surveillance endo s Multifocal, previously nodular, young, family hx of cancer, pathologically worried -> consider ablation Caveats about lack of data on decreasing cancer Non-dysplastic Ablation may be perferable, but we await further data 36 18

19 Can It Work in Primary GI Practices? Radiofrequency ablation of Barrett's esophagus: outcomes of 429 patients from a multicenter community practice registry. RFA performed in 4 community practices 76% non-dysplastic subjects Had follow-up in 338 (mean duration, 9 months) 72% had complete eradication of intestinal metaplasia 79% had complete eradication of dysplasia No perforations 2.1% stricture rate Endoscopy 2010; 42: