The Effect of Endoscopic Surveillance in Patients With Barrett’s Esophagus: A Systematic Review and Meta-analysis

doi:10.1053/j.gastro.2018.02.022

Gastroenterology

Volume 154, Issue 8, June 2018, Pages 2068-2086.e5

https://doi.org/10.1053/j.gastro.2018.02.022 Get rights and content

Background & Aims

Guidelines recommend endoscopic surveillance of patients with Barrett’s esophagus (BE) to identify those with dysplasia (a precursor of carcinoma) or early-stage esophageal adenocarcinoma (EAC) who can be treated endoscopically. However, it is unclear whether surveillance increases survival times of patients with BE. We performed a systematic review and meta-analysis to qualitatively and quantitatively examine evidence for the association of endoscopic surveillance in patients with BE with survival and other outcomes.

Methods

We searched publication databases for studies reporting the effects of endoscopic surveillance on mortality and other EAC-related outcomes. We reviewed randomized controlled trials, case-control studies, studies comparing patients with BE who received regular surveillance with those who did not receive regular surveillance, and studies comparing outcomes of patients with surveillance-detected EAC vs symptom-detected EACs. We performed a meta-analysis of surveillance studies to generate summary estimates using a random effects model. The primary aim was to examine the association of BE surveillance on EAC-related mortality. Secondary aims were to examine the association of BE surveillance with all-cause mortality and EAC stage at time of diagnosis.

Results

A single case-control study did not show any association between surveillance and EAC-related mortality. A meta-analysis of 4 cohort studies found that lower EAC-related and all-cause mortality were associated with regular surveillance (relative risk, 0.60; 95% CI, 0.50–0.71; hazard ratio, 0.75; 95% CI, 0.59–0.94). Meta-analysis of 12 cohort studies showed lower EAC-related and all-cause mortality among patients with surveillance-detected EAC vs symptom-detected EAC (relative risk, 0.73; 95% CI, 0.57–0.94; hazard ratio, 0.59; 95% CI, 0.45–0.76). Lead- and length-time bias adjustment substantially attenuated/eliminated the observed benefits. Surveillance was associated with detection of EAC at earlier stages. A randomized trial is underway to evaluate the effects of endoscopic surveillance on mortality in patients with BE.

Conclusions

In a systematic review and meta-analysis of the effects of surveillance in patients with BE, surveillance as currently performed was associated with detection of earlier-stage EAC and may provide a small survival benefit. However, the effects of confounding biases on these estimates are not fully defined and may completely or partially explain the observed differences between surveyed and unsurveyed patients.

Section snippets

Methods

This systematic review and meta-analysis was conducted in accordance with the Preferred Reporting items for Systematic Reviews and Meta-analyses (ie, PRISMA) guidelines.¹⁷

Results of the Systematic Review

Our initial search strategy yielded 1747 studies, with 19 articles eligible for inclusion in both the final qualitative and quantitative analysis (Figure 1).12, 13, 15, 16, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36 Given the heterogeneous study designs used in studies, we divided the studies into 4 different groups: group 1, RCT design; group 2, case-control study with matched control groups assessing EAC-related mortality; group 3, cohort study with well-defined BE

Discussion

Despite several limitations (sampling error, noncompliance with guidelines, poor interobserver agreement among pathologists in grading dysplasia,), all gastroenterology societies currently recommend endoscopic surveillance in BE, with the goal of accomplishing earlier detection of dysplasia or carcinoma,6, 43 which can then be treated endoscopically or surgically.

The ideal study to examine whether BE surveillance can be effective would be a randomized trial, which is currently ongoing in the

Acknowledgments

The authors would like to thank Patricia J. Erwin, MLS, librarian at the Mayo Clinic, who assisted in the development of the search strategy used in this meta-analysis.

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Cited by (121)

Advances in Screening for Barrett Esophagus and Esophageal Adenocarcinoma
2024, Mayo Clinic Proceedings
Esophageal adenocarcinoma (EAC), the primary form of esophageal cancer in the United States, is a lethal cancer with exponentially increasing incidence. Screening for Barrett esophagus (BE), the only known precursor to EAC, followed by endoscopic surveillance to detect dysplasia and early-stage EAC and subsequent endoscopic treatment (to prevent progression of dysplasia to EAC and to treat early-stage EAC effectively) is recommended by several society guidelines. Sedated endoscopy (the primary current tool for BE screening) is both invasive and expensive, limiting its widespread use. In this review, we aim to provide a comprehensive review of recent innovations in the nonendoscopic detection of BE and EAC. These include swallowable cell sampling devices combined with protein and epigenetic biomarkers (which are now guideline endorsed as alternatives to sedated endoscopy), tethered capsule endomicroscopy, emerging peripheral blood–sampled molecular biomarkers, and exhaled volatile organic compounds. We also summarize progress and challenges in assessing BE and EAC risk, which is an important complementary component of the process for the clinical implementation of these innovative nonendoscopic tools, and propose a new paradigm for the strategy to reduce EAC incidence and mortality.
Magnitude and Time-Trends of Post-Endoscopy Esophageal Adenocarcinoma and Post-Endoscopy Esophageal Neoplasia in a Population-Based Cohort Study: The Nordic Barrett's Esophagus Study
2023, Gastroenterology
Post-endoscopy esophageal adenocarcinoma (PEEC) and post-endoscopy esophageal neoplasia (PEEN) undermine early cancer detection in Barrett’s esophagus (BE). We aimed to assess the magnitude and conduct time-trend analysis of PEEC and PEEN among patients with newly diagnosed BE.
This population-based cohort study was conducted in Denmark, Finland, and Sweden between 2006 and 2020 and included 20,588 patients with newly diagnosed BE. PEEC and PEEN were defined as esophageal adenocarcinoma (EAC) or high-grade dysplasia (HGD)/EAC, respectively, diagnosed 30–365 days from BE diagnosis (index endoscopy). HGD/EAC diagnosed from 0–29 days and HGD/EAC diagnosed >365 days from BE diagnosis (incident HGD/EAC) were assessed. Patients were followed up until HGD/EAC, death, or end of study period. Incidence rates (IR) per 100,000 person-years with 95% confidence interval (95% CI) were calculated using Poisson regression.
Among 293 patients diagnosed with EAC, 69 (23.5%) were categorized as PEEC, 43 (14.7%) as index EAC, and 181 (61.8%) as incident EAC. The IRs/100,000 person-years for PEEC and incident EAC were 392 (95% CI, 309–496), and 208 (95% CI, 180–241), respectively. Among 279 patients diagnosed with HGD/EAC (Sweden only), 17.2% were categorized as PEEN, 14.6% as index HGD/EAC, and 68.1% as incident HGD/EAC. IRs/100,000 person-years for PEEN, and incident HGD/EAC were 421 (95% CI, 317–558), and 285 (95% CI, 247–328), respectively. Sensitivity analyses that varied time interval for occurrence of PEEC/PEEN demonstrated similar results. A time-trend analysis for IRs demonstrated rising incidence rates of PEEC/PEEN.
Almost a quarter of all EACs are detected within a year after an ostensibly negative upper endoscopy in patients with newly diagnosed BE. Interventions to improve detection may reduce PEEC/PEEN rates.
Professionals’ views on the justification for esophageal adenocarcinoma screening: A systematic literature search and qualitative analysis
2023, Preventive Medicine Reports
Screening for early esophageal adenocarcinoma (EAC), including screening for its precursor Barrett’s esophagus (BE), has the potential to reduce EAC-related mortality and morbidity. This literature review aimed to explore professionals’ views on the justification for EAC screening. A systematic search of Ovid Medline, EMBASE, and PsycInfo, from January 1, 2000 to September 22, 2022, identified 5 original studies and 63 expert opinion articles reporting professionals’ perspectives on EAC screening. Included articles were qualitatively analyzed using the framework method, which was deductively led by modernized screening principles. The analyses showed that many professionals are optimistic about technological advancements in BE detection and treatment. However, views on whether the societal burden of EAC merits screening were contradictory. In addition, knowledge of the long-term benefits and risks of EAC screening is still considered insufficient. There is no consensus on who to screen, how often to screen, which screening test to use, and how to manage non-dysplastic BE. Professionals further point out the need to develop technology that facilitates automated test sample processing and public education strategies that avoid causing disproportionately high cancer worry and social stigma. In conclusion, modernized screening principles are currently insufficiently fulfilled to justify widespread screening for EAC. Results from future clinical screening trials and risk prediction modeling studies may shift professionals’ thoughts regarding justification for EAC screening.
Estimated Burden of Screening for Barrett's Esophagus in the United States
2023, Gastroenterology
Surveillance in Barrett's Esophagus: Challenges, Progress, and Possibilities
2023, Gastroenterology
Endoscopic surveillance of Barrett’s esophagus, aiming to detect prevalent dysplasia and adenocarcinoma, followed by effective endoscopic treatment, is an integral part of the esophageal adenocarcinoma prevention paradigm. However, several limitations, such as the subtle appearance of dysplasia, sampling error (inherent in current surveillance protocols), and noncompliance with surveillance recommendations, lead to missed dysplasia and neoplasia, reducing the effectiveness of surveillance as currently practiced. Careful endoscopic assessment with high-resolution white-light endoscopy, dye-based or electronic chromoendoscopy, and comprehensive sampling of the BE mucosa, remains the cornerstone of endoscopic surveillance. Emerging innovations in this area span the gamut of more efficient sampling methods, advanced imaging tools, artificial intelligence, and molecular marker–powered approaches as adjuncts, to identify prevalent and predict incident dysplasia or adenocarcinoma. Development and implementation of validated quality indicators will allow additional advancement of this critical field. These approaches will hopefully enable efficient and effective cancer prevention and treatment.
Performance Characteristics of Screening Criteria to Identify Patients at Risk of Barrett's Esophagus in a Primary Care Setting
2023, Techniques and Innovations in Gastrointestinal Endoscopy
Several criteria have been developed for screening of Barrett's esophagus (BE). Previous studies are limited by analysis in highly selective populations. This study evaluated the performance of 4 criteria in identifying patients with BE from a primary care population.
This was a post-hoc analysis from a previous retrospective study reporting on BE screening rates of eligible patients in a large health system. Patients were included if they were screened in a primary care population for BE, were at risk for BE per 1 of the accepted criteria, and underwent screening with esophagogastroduodenoscopy. Sensitivity for BE was calculated for 4 screening criteria. These included criteria from the American College of Gastroenterology (ACG), American Society of Gastrointestinal Endoscopy (ASGE), European Society of Gastrointestinal Endoscopy (ESGE), and the Kunzmann model.
In a primary care population, 1077 patients were screened for BE with an esophagogastroduodenoscopy. BE was found in 105 (9.75%) patients. Positive predictive values and negative predictive values of ACG/ESGE, ASGE, and Kunzmann's criteria for BE on pathology were 9.9% and 90.45%, 9.12% and 89.22%, and 10.84% and 92.29%, respectively. The area under the receiver operating characteristic curve for ACG/ESGE, ASGE, and Kunzmann's criteria was 50.49%, 52.23%, and 54.04%, respectively. There was no statistically significant difference in the presence of BE on pathology among patients who did or did not meet ACG/ESGE, ASGE, or Kunzmann's criteria for BE screening.
Current BE screening criteria need optimization in a primary care setting. Use of a combination of criteria might capture the highest number of BE patients.

View all citing articles on Scopus

: This article has an accompanying continuing medical education activity, also eligible for MOC credit, on page e26. Learning Objective: Upon completion of this CME activity, successful learners will be able to explain the relationship between endoscopic surveillance of Barrett's esophagus and stage of esophageal cancer at presentation.

: Conflicts of interest These authors disclose the following: Nicholas J. Shaheen received research funding from CSA Medical, Medtronic, C2 Therapeutics, and CDx Medical, and Boston Scientific. Sachin Wani is a consultant for Medtronic, Boston Scientific. John M. Inadomi is a consultant for ChemImage Clinical Advisory Committee. Amitabh Chak received research funding from C2 Therapeutics. Prasad G. Iyer received research funding from Exact Sciences, C2 Therapeutics, and Medtronic. The remaining authors disclose no conflicts.

: Funding This research was supported by Public Health Service award U54 CA163060 (to Prasad G. Iyer, Amitabh Chak, and Apoorva Krishna Chandar), P50 CA150964 (Amitabh Chak and Apoorva Krishna Chandar), National Institutes of Health award K24DK100548 (Nicholas J. Shaheen), and National Institutes of Health Ninepoint grant (John M. Inadomi).

^∗: Authors share co-first authorship.

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Original ResearchFull Report: Clinical—Alimentary TractThe Effect of Endoscopic Surveillance in Patients With Barrett’s Esophagus: A Systematic Review and Meta-analysis

Background & Aims

Methods

Results

Conclusions

Section snippets

Methods

Results of the Systematic Review

Discussion

Acknowledgments

Lancet

Ann Oncol

Am J Gastroenterol

J Thorac Cardiovasc Surg

Am J Med

Gastrointest Endosc

Gastroenterology

Best Pract Res Clin Gastroenterol

Trends in esophageal adenocarcinoma incidence and mortality

Cancer

The role of overdiagnosis and reclassification in the marked increase of esophageal adenocarcinoma incidence

J Natl Cancer Inst

ACG clinical guideline: diagnosis and management of Barrett’s esophagus

Am J Gastroenterol

Ten criteria for effective screening: their application to multislice CT screening for pulmonary and colorectal cancers

AJR Am J Roentgenol

British Society of Gastroenterology guidelines on the diagnosis and management of Barrett’s oesophagus

Gut

Risk of malignant progression in Barrett’s esophagus patients: results from a large population-based study

J Natl Cancer Inst

Incidence of adenocarcinoma among patients with Barrett’s esophagus

New Engl J Med

Final results from 10 year cohort of patients undergoing surveillance for Barrett’s oesophagus: observational study

BMJ

Impact of endoscopic surveillance on mortality from Barrett’s esophagus-associated esophageal adenocarcinomas

Gastroenterology

Effect of surveillance of Barrett’s oesophagus on the clinical outcome of oesophageal cancer

Br J Surg

Association of prediagnosis endoscopy with stage and survival in adenocarcinoma of the esophagus and gastric cardia

Cancer

Impact of endoscopic biopsy surveillance of Barrett’s oesophagus on pathological stage and clinical outcome of Barrett’s carcinoma

Gut

Rigorous surveillance protocol increases detection of curable cancers associated with Barrett;s esophagus

Dig Dis Sci

The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration

Ann Intern Med

Original Research
Full Report: Clinical—Alimentary Tract
The Effect of Endoscopic Surveillance in Patients With Barrett’s Esophagus: A Systematic Review and Meta-analysis