Stratification of Barrett’s esophagus surveillance based on p53 immunohistochemistry: a cost-effectiveness analysis by an international collaborative group

Shyam Menon; Richard Norman; Prasad G. Iyer; Krish Ragunath

doi:10.1055/a-2317-8184

Endoscopy, Table of Contents

Endoscopy 2024; 56(10): 727-736
DOI: 10.1055/a-2317-8184

Original article

Stratification of Barrett’s esophagus surveillance based on p53 immunohistochemistry: a cost-effectiveness analysis by an international collaborative group

Shyam Menon

¹Gastroenterology, Royal Wolverhampton Hospitals NHS Trust, Wolverhampton, United Kingdom of Great Britain and Northern Ireland (Ringgold ID: RIN8692)

,

Richard Norman

²Health Economist, School of Population Health, Curtin University, Perth, Australia (Ringgold ID: RIN1649)

,

Prasad G. Iyer

³Gastroenterology and Hepatology, Mayo Clinic, Rochester, United States (Ringgold ID: RIN6915)

,

Krish Ragunath

⁴Curtin Medical School, Curtin University, Perth, Australia (Ringgold ID: RIN1649)

⁵Gastroenterology and Hepatology, Royal Perth Hospital, Perth, Australia (Ringgold ID: RIN6508)

› Author Affiliations

Abstract

Background Surveillance of nondysplastic Barrett’s esophagus (NDBE) is recommended to identify progression to dysplasia; however, the most cost-effective strategy remains unclear. Mutation of TP53 or aberrant expression of p53 have been associated with the development of dysplasia in BE. We sought to determine if surveillance intervals for BE could be stratified based on p53 expression.

Methods A Markov model was developed for NDBE. Patients with NDBE underwent p53 immunohistochemistry (IHC) and those with abnormal p53 expression underwent surveillance endoscopy at 1 year, while patients with normal p53 expression underwent surveillance in 3 years. Patients with dysplasia underwent endoscopic therapy and surveillance.

Results On base-case analysis, the strategy of stratifying surveillance based on abnormal p53 IHC was cost-effective relative to conventional surveillance and a natural history model, with an incremental cost-effectiveness ratio (ICER) of $8258 for p53 IHC-based surveillance. Both the conventional and p53-stratified surveillance strategies dominated the natural history model. On probabilistic sensitivity analysis, the p53 IHC strategy ($28 652; 16.78 quality-adjusted life years [QALYs]) was more cost-effective than conventional surveillance ($25 679; 16.17 QALYs) with a net monetary benefit of $306 873 compared with conventional surveillance ($297 642), with an ICER <$50 000 in 96% of iterations. The p53-stratification strategy was associated with a 14% reduction in the overall endoscopy burden and a 59% increase in dysplasia detection.

Conclusion A surveillance strategy for BE based on abnormal p53 IHC is cost-effective relative to a conventional surveillance strategy and is likely to be associated with higher rates of dysplasia diagnosis.

Full Text

References

References
1 Shaheen NJ, Falk GW, Iyer PG. et al. ACG Clinical Guideline: diagnosis and management of Barrett's esophagus. Am J Gastroenterol 2016; 111: 30-50; quiz 51
2 Obermannova R, Alsina M, Cervantes A. et al. Oesophageal cancer: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up. Ann Oncol 2022; 33: 992-1004
3 Dighe SG, Yan L, Mukherjee S. et al. Clinical and lifestyle-related prognostic indicators among esophageal adenocarcinoma patients receiving treatment at a comprehensive cancer center. Cancers (Basel) 2021; 13: 4653
4 Li S, Hoefnagel SJM, Krishnadath KK. Molecular biology and clinical management of esophageal adenocarcinoma. Cancers (Basel) 2023; 15: 5410
5 Shaheen NJ, Falk GW, Iyer PG. et al. Diagnosis and management of Barrett's esophagus: an updated ACG Guideline. Am J Gastroenterol 2022; 117: 559-587
6 Fitzgerald RC, di Pietro M, Ragunath K. et al. British Society of Gastroenterology guidelines on the diagnosis and management of Barrett's oesophagus. Gut 2014; 63: 7-42
7 Qumseya B, Sultan S. ASGE Standards Of Practice Committee. et al. ASGE guideline on screening and surveillance of Barrett's esophagus. Gastrointest Endosc 2019; 90: 335-359 e332
8 Whiteman DC, Appleyard M, Bahin FF. et al. Australian clinical practice guidelines for the diagnosis and management of Barrett's esophagus and early esophageal adenocarcinoma. J Gastroenterol Hepatol 2015; 30: 804-820
9 Codipilly DC, Chandar AK, Singh S. et al. The effect of endoscopic surveillance in patients with Barrett's esophagus: a systematic review and meta-analysis. Gastroenterology 2018; 154: 2068-2086 e2065
10 Sharma P, Falk GW, Weston AP. et al. Dysplasia and cancer in a large multicenter cohort of patients with Barrett's esophagus. Clin Gastroenterol Hepatol 2006; 4: 566-572
11 Sikkema M, Looman CW, Steyerberg EW. et al. Predictors for neoplastic progression in patients with Barrett's esophagus: a prospective cohort study. Am J Gastroenterol 2011; 106: 1231-1238
12 Buttar NS, Wang KK, Sebo TJ. et al. Extent of high-grade dysplasia in Barrett's esophagus correlates with risk of adenocarcinoma. Gastroenterology 2001; 120: 1630-1639
13 Bennett C, Moayyedi P, Corley DA. et al. BOB CAT: a large-scale review and Delphi consensus for management of Barrett's esophagus with no dysplasia, indefinite for, or low-grade dysplasia. Am J Gastroenterol 2015; 110: 662-682; quiz 683
14 Singh S, Manickam P, Amin AV. et al. Incidence of esophageal adenocarcinoma in Barrett's esophagus with low-grade dysplasia: a systematic review and meta-analysis. Gastrointest Endosc 2014; 79: 897-909 e894 ; quiz 983 e891–e893
15 Wani S, Puli SR, Shaheen NJ. et al. Esophageal adenocarcinoma in Barrett's esophagus after endoscopic ablative therapy: a meta-analysis and systematic review. Am J Gastroenterol 2009; 104: 502-513
16 Sinh P, Anaparthy R, Young PE. et al. Clinical outcomes in patients with a diagnosis of "indefinite for dysplasia" in Barrett's esophagus: a multicenter cohort study. Endoscopy 2015; 47: 669-674
17 Kestens C, Leenders M, Offerhaus GJ. et al. Risk of neoplastic progression in Barrett's esophagus diagnosed as indefinite for dysplasia: a nationwide cohort study. Endoscopy 2015; 47: 409-414
18 Krishnamoorthi R, Mohan BP, Jayaraj M. et al. Risk of progression in Barrett's esophagus indefinite for dysplasia: a systematic review and meta-analysis. Gastrointest Endosc 2020; 91: 3-10 e13
19 Shaheen NJ, Sharma P, Overholt BF. et al. Radiofrequency ablation in Barrett's esophagus with dysplasia. NEJM 2009; 360: 2277-2288
20 Peery AF, Shaheen NJ. Esophagus: endoscopic therapy for flat, dysplastic Barrett esophagus. Nat Rev Gastroenterol Hepatol 2011; 8: 186-187
21 Small AJ, Araujo JL, Leggett CL. et al. Radiofrequency ablation is associated with decreased neoplastic progression in patients with Barrett's esophagus and confirmed low-grade dysplasia. Gastroenterology 2015; 149: 567-576 e563 quiz e513–e564
22 Fudman DI, Lightdale CJ, Poneros JM. et al. Positive correlation between endoscopist radiofrequency ablation volume and response rates in Barrett's esophagus. Gastrointest Endosc 2014; 80: 71-77
23 Pouw RE, Klaver E, Phoa KN. et al. Radiofrequency ablation for low-grade dysplasia in Barrett's esophagus: long-term outcome of a randomized trial. Gastrointest Endosc 2020; 92: 569-574
24 Sami SS, Ravindran A, Kahn A. et al. Timeline and location of recurrence following successful ablation in Barrett's oesophagus: an international multicentre study. Gut 2019; 68: 1379-1385
25 Haidry RJ, Butt MA, Dunn JM. et al. Improvement over time in outcomes for patients undergoing endoscopic therapy for Barrett's oesophagus-related neoplasia: 6-year experience from the first 500 patients treated in the UK patient registry. Gut 2015; 64: 1192-1199
26 Phoa KN, Pouw RE, Bisschops R. et al. Multimodality endoscopic eradication for neoplastic Barrett oesophagus: results of an European multicentre study (EURO-II). Gut 2016; 65: 555-562
27 Haidry RJ, Lipman G, Banks MR. et al. Comparing outcome of radiofrequency ablation in Barrett's with high grade dysplasia and intramucosal carcinoma: a prospective multicenter UK registry. Endoscopy 2015; 47: 980-987
28 Hameeteman W, Tytgat GN, Houthoff HJ. et al. Barrett's esophagus: development of dysplasia and adenocarcinoma. Gastroenterology 1989; 96: 1249-1256
29 Das A, Wells C, Kim HJ. et al. An economic analysis of endoscopic ablative therapy for management of nondysplastic Barrett's esophagus. Endoscopy 2009; 41: 400-408
30 Inadomi JM, Saxena N. Screening and surveillance for Barrett's esophagus: is it cost-effective?. Dig Dis Sci 2018; 63: 2094-2104
31 Giovannini M, Bories E, Pesenti C. et al. Circumferential endoscopic mucosal resection in Barrett's esophagus with high-grade intraepithelial neoplasia or mucosal cancer. Preliminary results in 21 patients. Endoscopy 2004; 36: 782-787
32 Hirst NG, Gordon LG, Whiteman DC. et al. Is endoscopic surveillance for non-dysplastic Barrett's esophagus cost-effective? Review of economic evaluations. J Gastroenterol Hepatol 2011; 26: 247-254
33 Kastelein F, van Olphen S, Steyerberg EW. et al. Surveillance in patients with long-segment Barrett's oesophagus: a cost-effectiveness analysis. Gut 2015; 64: 864-871
34 Omidvari AH, Ali A, Hazelton WD. et al. Optimizing management of patients with Barrett's esophagus and low-grade or no dysplasia based on comparative modeling. Clin Gastroenterol Hepatol 2020; 18: 1961-1969
35 Gordon LG, Mayne GC, Hirst NG. et al. Cost-effectiveness of endoscopic surveillance of non-dysplastic Barrett's esophagus. Gastrointest Endosc 2014; 79: 242-256 e246
36 Galipeau PC, Li X, Blount PL. et al. NSAIDs modulate CDKN2A, TP53, and DNA content risk for progression to esophageal adenocarcinoma. PLoS Med 2007; 4: e67
37 Stachler MD, Camarda ND, Deitrick C. et al. Detection of mutations in Barrett's esophagus before progression to high-grade dysplasia or adenocarcinoma. Gastroenterology 2018; 155: 156-167
38 Koppert LB, Wijnhoven BP, van Dekken H. et al. The molecular biology of esophageal adenocarcinoma. J Surg Oncol 2005; 92: 169-190
39 Polkowski W, van Lanschot JJ, Ten Kate FJ. et al. The value of p53 and Ki67 as markers for tumour progression in the Barrett's dysplasia-carcinoma sequence. Surg Oncol 1995; 4: 163-171
40 Kastelein F, Biermann K, Steyerberg EW. et al. Aberrant p53 protein expression is associated with an increased risk of neoplastic progression in patients with Barrett's oesophagus. Gut 2013; 62: 1676-1683
41 Davelaar AL, Calpe S, Lau L. et al. Aberrant TP53 detected by combining immunohistochemistry and DNA-FISH improves Barrett's esophagus progression prediction: a prospective follow-up study. Genes Chromosomes Cancer 2015; 54: 82-90
42 Snyder P, Dunbar K, Cipher DJ. et al. Aberrant p53 immunostaining in Barrett's esophagus predicts neoplastic progression: systematic review and meta-analyses. Dig Dis Sci 2019; 64: 1089-1097
43 Redston M, Noffsinger A, Kim A. et al. Abnormal TP53 predicts risk of progression in patients with Barrett's esophagus regardless of a diagnosis of dysplasia. Gastroenterology 2022; 162: 468-481
44 Shaheen NJ, Falk GW, Iyer PG. et al. ACG Clinical Guideline: Diagnosis and management of Barrett’s esophagus. Am J Gastroenterol 2016; 111: 30-50
45 Pace M. European Commission, Eurostat. et al. Revision of the European Standard Population – Report of Eurostat's task force – 2013 edn. Accessed May 20, 2024 at: https://data.europa.eu/doi10.2785/11470
46 Qumseya BJ, Wani S, Desai M. et al. Adverse events after radiofrequency ablation in patients with Barrett's esophagus: a systematic review and meta-analysis. Clin Gastroenterol Hepatol 2016; 14: 1086-1095 e1086
47 ASGE. Adverse events of upper GI endoscopy. Gastrointest Endosc 2012; 76: 707-718
48 Menon S, Norman R, Mannath J. et al. Comparative cost-effectiveness of three post-radiofrequency ablation surveillance intervals for Barrett's esophagus. Endosc Int Open 2022; 10: E1053-E1064
49 Tramontano AC, Chen Y, Watson TR. et al. Esophageal cancer treatment costs by phase of care and treatment modality, 2000–2013. Cancer Med 2019; 8: 5158-5172
50 McDougall JA, Furnback WE, Wang BCM. et al. Understanding the global measurement of willingness to pay in health. J Mark Access Health Policy 2020; 8: 1717030
51 Hur C, Choi SE, Rubenstein JH. et al. The cost effectiveness of radiofrequency ablation for Barrett's esophagus. Gastroenterology 2012; 143: 567-575
52 Pollit V, Graham D, Leonard C. et al. A cost-effectiveness analysis of endoscopic eradication therapy for management of dysplasia arising in patients with Barrett's oesophagus in the United Kingdom. Curr Med Res Opin 2019; 35: 805-815
53 Boger PC, Turner D, Roderick P. et al. A UK-based cost-utility analysis of radiofrequency ablation or oesophagectomy for the management of high-grade dysplasia in Barrett's oesophagus. Aliment Pharmacol Ther 2010; 32: 1332-1342
54 Rastogi A, Puli S, El-Serag HB. et al. Incidence of esophageal adenocarcinoma in patients with Barrett's esophagus and high-grade dysplasia: a meta-analysis. Gastrointest Endosc 2008; 67: 394-398
55 Curvers WL, ten Kate FJ, Krishnadath KK. et al. Low-grade dysplasia in Barrett's esophagus: overdiagnosed and underestimated. Am J Gastroenterol 2010; 105: 1523-1530
56 Krishnamoorthi R, Borah B, Heien H. et al. Rates and predictors of progression to esophageal carcinoma in a large population-based Barrett's esophagus cohort. Gastrointest Endosc 2016; 84: 40-46 e47
57 Fujii-Lau LL, Cinnor B, Shaheen N. et al. Recurrence of intestinal metaplasia and early neoplasia after endoscopic eradication therapy for Barrett's esophagus: a systematic review and meta-analysis. Endosc Int Open 2017; 5: E430-E449
58 Cotton CC, Haidry R, Thrift AP. et al. Development of evidence-based surveillance intervals after radiofrequency ablation of Barrett's esophagus. Gastroenterology 2018; 155: 316-326 e316
59 Whitehead SJ, Ali S. Health outcomes in economic evaluation: the QALY and utilities. Br Med Bull 2010; 96: 5-21
60 Weinstein MC, Stason WB. Foundations of cost-effectiveness analysis for health and medical practices. NEJM 1977; 31: 716-721
61 CMS. Centers for Medicare & Medicaid Services. In: Centers for Medicare & Medicaid Services; 2022 DOI: 10.3122/jabfm.2021.S1.200450 PubMed: 33622810.
62 Cantor SB. Cost-effectiveness analysis, extended dominance, and ethics: a quantitative assessment. Med Decis Making 1994; 14: 259-265
63 Provenzale D, Schmitt C, Wong JB. Barrett's esophagus: a new look at surveillance based on emerging estimates of cancer risk. Am J Gastroenterol 1999; 94: 2043-2053
64 Inadomi JM, Somsouk M, Madanick RD. et al. A cost-utility analysis of ablative therapy for Barrett's esophagus. Gastroenterology 2009; 136: 2101-2114 e2101
65 Sonnenberg A, Soni A, Sampliner RE. Medical decision analysis of endoscopic surveillance of Barrett's oesophagus to prevent oesophageal adenocarcinoma. Aliment Pharmacol Ther 2002; 16: 41-50
66 Garside R, Pitt M, Somerville M. et al. Surveillance of Barrett's oesophagus: exploring the uncertainty through systematic review, expert workshop and economic modelling. Health Technol Assess 2006; 10: 1-142 iii–iv
67 Sonnenberg A, Fennerty MB. Medical decision analysis of chemoprevention against esophageal adenocarcinoma. Gastroenterology 2003; 124: 1758-1766
68 Gray NA, Odze RD, Spechler SJ. Buried metaplasia after endoscopic ablation of Barrett's esophagus: a systematic review. Am J Gastroenterol 2011; 106: 1899-1908 quiz 1909
69 Corley DA, Levin TR, Habel LA. et al. Surveillance and survival in Barrett's adenocarcinomas: a population-based study. Gastroenterology 2002; 122: 633-640
70 di Pietro M, Fitzgerald RC. BSG Barret’s Guidelines Working Group. Revised British Society of Gastroenterology recommendation on the diagnosis and management of Barrett's oesophagus with low-grade dysplasia. Gut 2018; 67: 392-393
71 Ganz RA, Overholt BF, Sharma VK. et al. Circumferential ablation of Barrett's esophagus that contains high-grade dysplasia: a U.S. Multicenter Registry. Gastrointest Endosc 2008; 68: 35-40
72 Critchley-Thorne RJ, Duits LC, Prichard JW. et al. A tissue systems pathology assay for high-risk Barrett's esophagus. Cancer Epidemiol Biomarkers Prev 2016; 25: 958-968
73 Kaye PV. p53 Immunohistochemistry as a biomarker of dysplasia and neoplastic progression in Barrett's oesophagus. Diagn Histopathol 2015; 21: 89-98
74 Brankley SM, Halling KC, Jenkins SM. et al. Fluorescence in situ hybridization identifies high risk Barrett's patients likely to develop esophageal adenocarcinoma. Dis Esophagus 2016; 29: 513-519
75 Dorer R, Odze RD. AMACR immunostaining is useful in detecting dysplastic epithelium in Barrett's esophagus, ulcerative colitis, and Crohn's disease. The American journal of surgical pathology 2006; 30: 871-877
76 Sabo E, Beck AH, Montgomery EA. et al. Computerized morphometry as an aid in determining the grade of dysplasia and progression to adenocarcinoma in Barrett's esophagus. Lab Invest 2006; 86: 1261-1271
77 Hao J, Critchley-Thorne R, Diehl DL. et al. A cost-effectiveness analysis of an adenocarcinoma risk prediction multi-biomarker assay for patients with Barrett's esophagus. Clinicoecon Outcomes Res 2019; 11: 623-635
78 Iyer PG, Codipilly DC, Chandar AK. et al. Prediction of progression in Barrett's esophagus using a tissue systems pathology test: a pooled analysis of international multicenter studies. Clin Gastroenterol Hepatol 2022; 20: 2772-2779 e2778

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Supplementary Material