Population-Based Estimates of Cancer and Mortality in Barrett's Esophagus: Implications for the Future
Authors: Sachin Wani
Journal: Clinical Gastroenterology and Hepatology (2011)

Barrett's esophagus (BE) is a well-established premalignant condition for the development of esophageal adenocarcinoma (EAC), a cancer with a rapidly rising incidence in the Western world associated with a dismal 5-year survival rate.1Pohl H. Welch H.G. The role of overdiagnosis and reclassification in the marked increase of esophageal adenocarcinoma incidence.J Natl Cancer Inst. 2005; 97: 142-146Crossref PubMed Scopus (1082) Google Scholar Progression of BE to EAC occurs in a probabilistic manner and involves a series of pathologic changes from nondysplastic BE (NDBE) to low-grade dysplasia (LGD), high-grade dysplasia (HGD), and finally to EAC. At the present time, the histologic classification of dysplasia is the best biomarker for predicting progression to EAC and HGD is associated with the greatest risk for malignant transformation. Although the incidence of EAC in patients with NDBE is much higher than in the general population, only a minority develop EAC with an annual incidence of 0.5% to 0.6%.2Shaheen N.J. Crosby M.A. Bozymski E.M. et al.Is there publication bias in the reporting of cancer risk in Barrett's esophagus?.Gastroenterology. 2000; 119: 333-338Abstract Full Text Full Text PDF PubMed Scopus (734) Google Scholar, 3Wani S. Puli S.R. Shaheen N.J. et al.Esophageal adenocarcinoma in Barrett's esophagus after endoscopic ablative therapy: a meta-analysis and systematic review.Am J Gastroenterol. 2009; 104: 502-513Crossref PubMed Scopus (167) Google Scholar In fact, data from recent large cohort studies confirm the very low rate of progression of NDBE to cancer (annual incidence of 0.3% per year), rates lower than those previously reported.4Wani S. Falk G. Hall M. et al.Patients with nondysplastic Barrett's esophagus have low risks for developing dysplasia or esophageal adenocarcinoma.Clin Gastroenterol Hepatol. 2011; 9: 220-227Abstract Full Text Full Text PDF PubMed Scopus (170) Google Scholar, 5de Jonge P.J. van Blankenstein M. Looman C.W. et al.Risk of malignant progression in patients with Barrett's oesophagus: a Dutch nationwide cohort study.Gut. 2010; 59: 1030-1036Crossref PubMed Scopus (231) Google ScholarIn this issue of Clinical Gastroenterology and Hepatology, Schouten et al6Schouten L.J. Steevens J. Huysentruyt C.J.R. et al.Total cancer incidence and overall mortality are not increased among patients with Barrett's esophagus.Clin Gastroenterol Hepatol. 2011; 9: 754-761Abstract Full Text Full Text PDF PubMed Scopus (37) Google Scholar aimed to answer 3 important questions: the incidence of EAC, incidence of other cancers, and cause-specific mortality in a population-based cohort of BE patients. This study was conducted using a cohort of patients from the Netherlands Cohort Study on Diet and Cancer that included over 100,000 subjects. BE patients were identified by record-linkage to the national pathology registry, a central pathology database. Follow-up in this study was accomplished by linkage to the population, cancer, and causes of death registry. In a cohort of 605 BE cases with a mean follow-up of 6 years, the annual incidence rate of EAC in patients with NDBE (n = 493) was 0.3% (95% confidence interval [CI], 0.1–0.54). A low rate of progression to EAC (annual incidence of 0.41%; 95% CI, 0.01–1.44) was also reported in patients with LGD (n = 92). The presence of BE was not associated with an increased incidence of other cancers such as small bowel, pancreatic, and colon cancer. Finally, the diagnosis of BE did not have any impact on the overall mortality even after exclusion of esophageal and gastric cancers.Where do we stand in terms of natural history of NDBE? Results from this study add to the growing body of literature reporting the incidence of EAC in patients with NDBE. In a recent study, we reported the incidence of dysplasia and EAC from a multicenter outcomes project of a large cohort of BE patients (Barrett's esophagus study).4Wani S. Falk G. Hall M. et al.Patients with nondysplastic Barrett's esophagus have low risks for developing dysplasia or esophageal adenocarcinoma.Clin Gastroenterol Hepatol. 2011; 9: 220-227Abstract Full Text Full Text PDF PubMed Scopus (170) Google Scholar Of the 1204 patients that met inclusion criteria, incidence of EAC was 0.27% per year (95% CI, 0.17–0.43), HGD was 0.48% per year (95% CI, 0.34–0.68), and HGD/EAC was 0.63% per year (95% CI, 0.47–0.86). De Jonge et al reported the incidence of EAC in a nationwide cohort of BE patients in the Netherlands also using the same centralized pathology database as the current study.5de Jonge P.J. van Blankenstein M. Looman C.W. et al.Risk of malignant progression in patients with Barrett's oesophagus: a Dutch nationwide cohort study.Gut. 2010; 59: 1030-1036Crossref PubMed Scopus (231) Google Scholar Results of this study, which included 16,333 patients with nondysplastic Barrett's esophagus and LGD with a total follow-up period of 78,480 patient-years, reported an annual incidence rate of 0.58% per year (95% CI, 0.47–0.72) using an end point of HGD/EAC as malignant progression and an annual EAC risk of 0.43% (95% CI, 0.34–0.55). For patients with NDBE, the annual incidence rate of EAC alone was 0.39% per year (95% CI, 0.29–0.51). Thus, these contemporary studies report a much lower incidence of dysplasia and EAC among patients with NDBE than previously reported.This study is also notable for providing an estimate of the rate of progression of LGD to EAC. Unfortunately, data regarding progression from LGD to both HGD/EAC combined or just EAC are highly variable ranging from 0.6% to 13.4% per year.7Wani S. Mathur S. Sharma P. How to manage a Barrett's esophagus patient with low-grade dysplasia.Clin Gastroenterol Hepatol. 2009; 7: 27-32Abstract Full Text Full Text PDF PubMed Scopus (29) Google Scholar, 8Curvers W.L. ten Kate F.J. Krishnadath K.K. et al.Low-grade dysplasia in Barrett's esophagus: overdiagnosed and underestimated.Am J Gastroenterol. 2010; 105: 1523-1530Crossref PubMed Scopus (362) Google Scholar Results from the Barrett's esophagus study reported a low incidence of EAC (0.44% per year; 95% CI, 0.2–0.98) among 210 patients with LGD followed for a mean of 6.2 years. The annual incidence of HGD was 1.6% (95% CI, 1.05–2.46) and 1.83% (95% CI, 1.23–2.74) using a combined end point of HGD/EAC.9Wani S. Falk G.W. Sampliner R.E. et al.Low grade dysplasia is a poor marker for cancer progression in patients with Barrett's esophagus: preliminary results from a large, multicenter, cohort study.Gastroenterology. 2009; 136: A592Google Scholar Similar results were reported from the large Dutch study by De Jonge et al with an annual EAC incidence rate of 0.7% (95% CI, 0.45–1.3) and 1.06% (95% CI, 0.68–1.67) using a combined end point of HGD/EAC.5de Jonge P.J. van Blankenstein M. Looman C.W. et al.Risk of malignant progression in patients with Barrett's oesophagus: a Dutch nationwide cohort study.Gut. 2010; 59: 1030-1036Crossref PubMed Scopus (231) Google Scholar These results also highlight the overall low incidence rates of EAC in patients with LGD (similar to NDBE).Another notable feature of the current article is the estimate of cause-specific mortality in this population-based cohort of BE patients. Two other population-based studies have confirmed the findings of lack of increased mortality in BE patients as reported in this study.10Anderson L.A. Murray L.J. Murphy S.J. et al.Mortality in Barrett's oesophagus: results from a population based study.Gut. 2003; 52: 1081-1084Crossref PubMed Scopus (137) Google Scholar, 11Jung K.W. Talley N.J. Romero Y. et al.Epidemiology and natural history of intestinal metaplasia of the gastroesophageal junction and Barrett's esophagus: a population-based study.Am J Gastroenterol. 2011; (in press)Google Scholar A recent study from Olmsted County, Minnesota that included 401 patients with BE reported no difference in the overall survival in subjects with BE compared with expected survival in similar age- and sex-distributed populations.11Jung K.W. Talley N.J. Romero Y. et al.Epidemiology and natural history of intestinal metaplasia of the gastroesophageal junction and Barrett's esophagus: a population-based study.Am J Gastroenterol. 2011; (in press)Google Scholar Consistent with these results, a previously reported meta-analysis reported an exceedingly low esophageal cancer-related mortality of 3 per 1000 patient-years and the vast majority of patients (>90%) died due to other etiologies (cardiovascular disease being the most common cause).12Sikkema M. de Jonge P.J. Steyerberg E.W. et al.Risk of esophageal adenocarcinoma and mortality in patients with Barrett's esophagus: a systematic review and meta-analysis.Clin Gastroenterol Hepatol. 2010; 8: 235-244Abstract Full Text Full Text PDF PubMed Scopus (290) Google ScholarThe major strength of this study is the population-based estimates of cancer and mortality in BE. There are certain limitations of this study that merit mention. This study was primarily conducted using a pathology database and did not involve review of endoscopy reports. It is unclear how many patients had evidence of columnar lined esophagus versus those with an “abnormal” or “irregular Z line.” It is possible that some proportion of these subjects were misclassified as having BE and, hence, the cancer incidence and mortality rates are biased toward the null by some unknown magnitude. Patients with intestinal metaplasia of the gastroesophageal junction or gastric cardia not only have distinct clinical characteristics but also have a substantially lower cancer progression risk compared with those with BE.11Jung K.W. Talley N.J. Romero Y. et al.Epidemiology and natural history of intestinal metaplasia of the gastroesophageal junction and Barrett's esophagus: a population-based study.Am J Gastroenterol. 2011; (in press)Google Scholar The lack of endoscopic correlation also precludes assessment of which patients (dysplastic/NDBE) underwent endoscopic eradication therapies which may have impacted the overall progression rates to EAC. It is also unclear if histopathology of all neoplastic cases was reviewed by expert gastrointestinal pathologists. Although an overall rate of progression to EAC in patients with NDBE has been reported, this study does not provide an estimate to the combined end point of HGD and EAC. It is imperative that all trials reporting on the natural history of BE report estimates of this end point as HGD is now established as an “actionable” diagnosis and progression to HGD and early EAC merits the same intervention—endoscopic eradication therapies.Results from these recent studies have several important implications. Most importantly, this study provides important estimates in making decisions in the management of this premalignant condition for patients, physicians, and policymakers. Based on these low rates of progression to EAC, should we cease to enroll patients with NDBE in surveillance programs? The answer is no. These data are unable to assess the magnitude of the preventive effect of surveillance on cancer incidence and mortality rates. Without level 1 evidence comparing surveillance to a group not undergoing surveillance, the impact of surveillance on these results remains unclear. However, because the vast majority of patients are cancer-free during long-term follow-up, lengthening of surveillance intervals to possibly every 5 years for NDBE patients should be considered. Cost-effectiveness analysis, including the recent analysis comparing endoscopic eradication therapy for NDBE and LGD with surveillance,13Inadomi J.M. Somsouk M. Madanick R.D. et al.A cost-utility analysis of ablative therapy for Barrett's esophagus.Gastroenterology. 2009; 136: 2101-2114Abstract Full Text Full Text PDF PubMed Scopus (150) Google Scholar have used rates of progression to EAC that are almost twice of what has been reported in these recent studies. Appraisal of current modeling studies using these incidence rates should be performed in future studies. These results add fuel to the controversy whether virtually all BE patients should undergo endoscopic eradication therapies, regardless of presence of dysplasia. Arguments against uniform ablation of all patients with NDBE include lack of efficacy data demonstrating a reduction in the long-term risk of EAC, the large number of patients requiring endoscopic eradication therapies to prevent 1 case of cancer coupled with a very low risk of progression to cancer, the ongoing need for surveillance postablation, recurrence of intestinal metaplasia with the need for maintenance therapies, and the profound economic implications in treating millions of NDBE patients. Even if we assume that ablation of all NDBE patients leads to a reduction in the long-term risk of EAC, benefits in the form of improved survival would be hard to demonstrate as there is no difference in overall mortality rates in patients with NDBE compared with the general population. In fact, in a recent medical position statement, the American Gastroenterological Association has recommended endoscopic eradication therapy for the treatment of patients with confirmed HGD but not for the general population with NDBE.14Spechler S.J. Sharma P. Souza R.F. et al.American Gastroenterological Association medical position statement on the management of Barrett's esophagus.Gastroenterology. 2011; 140: 1084-1091Abstract Full Text Full Text PDF PubMed Scopus (502) Google Scholar This needs to be clarified in a randomized controlled trial comparing endoscopic eradication therapy compared with surveillance in this group of patients. A discussion of implications and controversies surrounding the diagnosis of LGD (variable natural history, significant degree of interobserver agreement even among expert pathologists) and its role in risk stratification is beyond the scope of this editorial. Given the low overall risk of progression of LGD to EAC (rates similar to NDBE), routine endoscopic ablation of all patients with LGD would be difficult to justify.In summary, results from this population-based study highlight the low incidence of cancer in patients with NDBE and LGD; annual incidence of 0.3% and 0.4%, respectively, and the diagnosis of BE has no impact on overall mortality rates. Results from this and other recent studies should temper enthusiasm for wholesale application for endoscopic eradication therapies for patients with NDBE and LGD. The future lies in the creation of a large nation-wide Barrett's consortium that validates these results and provides a comprehensive evaluation of risk factors (clinical characteristics and biomarkers) for progression. This will allow us to accurately risk-stratify patients according to their potential for neoplastic progression using statistical prediction models. These data would then guide in making accurate patient-centered decisions regarding management: surveillance, chemoprevention, or endoscopic eradication therapies. Barrett's esophagus (BE) is a well-established premalignant condition for the development of esophageal adenocarcinoma (EAC), a cancer with a rapidly rising incidence in the Western world associated with a dismal 5-year survival rate.1Pohl H. Welch H.G. The role of overdiagnosis and reclassification in the marked increase of esophageal adenocarcinoma incidence.J Natl Cancer Inst. 2005; 97: 142-146Crossref PubMed Scopus (1082) Google Scholar Progression of BE to EAC occurs in a probabilistic manner and involves a series of pathologic changes from nondysplastic BE (NDBE) to low-grade dysplasia (LGD), high-grade dysplasia (HGD), and finally to EAC. At the present time, the histologic classification of dysplasia is the best biomarker for predicting progression to EAC and HGD is associated with the greatest risk for malignant transformation. Although the incidence of EAC in patients with NDBE is much higher than in the general population, only a minority develop EAC with an annual incidence of 0.5% to 0.6%.2Shaheen N.J. Crosby M.A. Bozymski E.M. et al.Is there publication bias in the reporting of cancer risk in Barrett's esophagus?.Gastroenterology. 2000; 119: 333-338Abstract Full Text Full Text PDF PubMed Scopus (734) Google Scholar, 3Wani S. Puli S.R. Shaheen N.J. et al.Esophageal adenocarcinoma in Barrett's esophagus after endoscopic ablative therapy: a meta-analysis and systematic review.Am J Gastroenterol. 2009; 104: 502-513Crossref PubMed Scopus (167) Google Scholar In fact, data from recent large cohort studies confirm the very low rate of progression of NDBE to cancer (annual incidence of 0.3% per year), rates lower than those previously reported.4Wani S. Falk G. Hall M. et al.Patients with nondysplastic Barrett's esophagus have low risks for developing dysplasia or esophageal adenocarcinoma.Clin Gastroenterol Hepatol. 2011; 9: 220-227Abstract Full Text Full Text PDF PubMed Scopus (170) Google Scholar, 5de Jonge P.J. van Blankenstein M. Looman C.W. et al.Risk of malignant progression in patients with Barrett's oesophagus: a Dutch nationwide cohort study.Gut. 2010; 59: 1030-1036Crossref PubMed Scopus (231) Google Scholar In this issue of Clinical Gastroenterology and Hepatology, Schouten et al6Schouten L.J. Steevens J. Huysentruyt C.J.R. et al.Total cancer incidence and overall mortality are not increased among patients with Barrett's esophagus.Clin Gastroenterol Hepatol. 2011; 9: 754-761Abstract Full Text Full Text PDF PubMed Scopus (37) Google Scholar aimed to answer 3 important questions: the incidence of EAC, incidence of other cancers, and cause-specific mortality in a population-based cohort of BE patients. This study was conducted using a cohort of patients from the Netherlands Cohort Study on Diet and Cancer that included over 100,000 subjects. BE patients were identified by record-linkage to the national pathology registry, a central pathology database. Follow-up in this study was accomplished by linkage to the population, cancer, and causes of death registry. In a cohort of 605 BE cases with a mean follow-up of 6 years, the annual incidence rate of EAC in patients with NDBE (n = 493) was 0.3% (95% confidence interval [CI], 0.1–0.54). A low rate of progression to EAC (annual incidence of 0.41%; 95% CI, 0.01–1.44) was also reported in patients with LGD (n = 92). The presence of BE was not associated with an increased incidence of other cancers such as small bowel, pancreatic, and colon cancer. Finally, the diagnosis of BE did not have any impact on the overall mortality even after exclusion of esophageal and gastric cancers. Where do we stand in terms of natural history of NDBE? Results from this study add to the growing body of literature reporting the incidence of EAC in patients with NDBE. In a recent study, we reported the incidence of dysplasia and EAC from a multicenter outcomes project of a large cohort of BE patients (Barrett's esophagus study).4Wani S. Falk G. Hall M. et al.Patients with nondysplastic Barrett's esophagus have low risks for developing dysplasia or esophageal adenocarcinoma.Clin Gastroenterol Hepatol. 2011; 9: 220-227Abstract Full Text Full Text PDF PubMed Scopus (170) Google Scholar Of the 1204 patients that met inclusion criteria, incidence of EAC was 0.27% per year (95% CI, 0.17–0.43), HGD was 0.48% per year (95% CI, 0.34–0.68), and HGD/EAC was 0.63% per year (95% CI, 0.47–0.86). De Jonge et al reported the incidence of EAC in a nationwide cohort of BE patients in the Netherlands also using the same centralized pathology database as the current study.5de Jonge P.J. van Blankenstein M. Looman C.W. et al.Risk of malignant progression in patients with Barrett's oesophagus: a Dutch nationwide cohort study.Gut. 2010; 59: 1030-1036Crossref PubMed Scopus (231) Google Scholar Results of this study, which included 16,333 patients with nondysplastic Barrett's esophagus and LGD with a total follow-up period of 78,480 patient-years, reported an annual incidence rate of 0.58% per year (95% CI, 0.47–0.72) using an end point of HGD/EAC as malignant progression and an annual EAC risk of 0.43% (95% CI, 0.34–0.55). For patients with NDBE, the annual incidence rate of EAC alone was 0.39% per year (95% CI, 0.29–0.51). Thus, these contemporary studies report a much lower incidence of dysplasia and EAC among patients with NDBE than previously reported. This study is also notable for providing an estimate of the rate of progression of LGD to EAC. Unfortunately, data regarding progression from LGD to both HGD/EAC combined or just EAC are highly variable ranging from 0.6% to 13.4% per year.7Wani S. Mathur S. Sharma P. How to manage a Barrett's esophagus patient with low-grade dysplasia.Clin Gastroenterol Hepatol. 2009; 7: 27-32Abstract Full Text Full Text PDF PubMed Scopus (29) Google Scholar, 8Curvers W.L. ten Kate F.J. Krishnadath K.K. et al.Low-grade dysplasia in Barrett's esophagus: overdiagnosed and underestimated.Am J Gastroenterol. 2010; 105: 1523-1530Crossref PubMed Scopus (362) Google Scholar Results from the Barrett's esophagus study reported a low incidence of EAC (0.44% per year; 95% CI, 0.2–0.98) among 210 patients with LGD followed for a mean of 6.2 years. The annual incidence of HGD was 1.6% (95% CI, 1.05–2.46) and 1.83% (95% CI, 1.23–2.74) using a combined end point of HGD/EAC.9Wani S. Falk G.W. Sampliner R.E. et al.Low grade dysplasia is a poor marker for cancer progression in patients with Barrett's esophagus: preliminary results from a large, multicenter, cohort study.Gastroenterology. 2009; 136: A592Google Scholar Similar results were reported from the large Dutch study by De Jonge et al with an annual EAC incidence rate of 0.7% (95% CI, 0.45–1.3) and 1.06% (95% CI, 0.68–1.67) using a combined end point of HGD/EAC.5de Jonge P.J. van Blankenstein M. Looman C.W. et al.Risk of malignant progression in patients with Barrett's oesophagus: a Dutch nationwide cohort study.Gut. 2010; 59: 1030-1036Crossref PubMed Scopus (231) Google Scholar These results also highlight the overall low incidence rates of EAC in patients with LGD (similar to NDBE). Another notable feature of the current article is the estimate of cause-specific mortality in this population-based cohort of BE patients. Two other population-based studies have confirmed the findings of lack of increased mortality in BE patients as reported in this study.10Anderson L.A. Murray L.J. Murphy S.J. et al.Mortality in Barrett's oesophagus: results from a population based study.Gut. 2003; 52: 1081-1084Crossref PubMed Scopus (137) Google Scholar, 11Jung K.W. Talley N.J. Romero Y. et al.Epidemiology and natural history of intestinal metaplasia of the gastroesophageal junction and Barrett's esophagus: a population-based study.Am J Gastroenterol. 2011; (in press)Google Scholar A recent study from Olmsted County, Minnesota that included 401 patients with BE reported no difference in the overall survival in subjects with BE compared with expected survival in similar age- and sex-distributed populations.11Jung K.W. Talley N.J. Romero Y. et al.Epidemiology and natural history of intestinal metaplasia of the gastroesophageal junction and Barrett's esophagus: a population-based study.Am J Gastroenterol. 2011; (in press)Google Scholar Consistent with these results, a previously reported meta-analysis reported an exceedingly low esophageal cancer-related mortality of 3 per 1000 patient-years and the vast majority of patients (>90%) died due to other etiologies (cardiovascular disease being the most common cause).12Sikkema M. de Jonge P.J. Steyerberg E.W. et al.Risk of esophageal adenocarcinoma and mortality in patients with Barrett's esophagus: a systematic review and meta-analysis.Clin Gastroenterol Hepatol. 2010; 8: 235-244Abstract Full Text Full Text PDF PubMed Scopus (290) Google Scholar The major strength of this study is the population-based estimates of cancer and mortality in BE. There are certain limitations of this study that merit mention. This study was primarily conducted using a pathology database and did not involve review of endoscopy reports. It is unclear how many patients had evidence of columnar lined esophagus versus those with an “abnormal” or “irregular Z line.” It is possible that some proportion of these subjects were misclassified as having BE and, hence, the cancer incidence and mortality rates are biased toward the null by some unknown magnitude. Patients with intestinal metaplasia of the gastroesophageal junction or gastric cardia not only have distinct clinical characteristics but also have a substantially lower cancer progression risk compared with those with BE.11Jung K.W. Talley N.J. Romero Y. et al.Epidemiology and natural history of intestinal metaplasia of the gastroesophageal junction and Barrett's esophagus: a population-based study.Am J Gastroenterol. 2011; (in press)Google Scholar The lack of endoscopic correlation also precludes assessment of which patients (dysplastic/NDBE) underwent endoscopic eradication therapies which may have impacted the overall progression rates to EAC. It is also unclear if histopathology of all neoplastic cases was reviewed by expert gastrointestinal pathologists. Although an overall rate of progression to EAC in patients with NDBE has been reported, this study does not provide an estimate to the combined end point of HGD and EAC. It is imperative that all trials reporting on the natural history of BE report estimates of this end point as HGD is now established as an “actionable” diagnosis and progression to HGD and early EAC merits the same intervention—endoscopic eradication therapies. Results from these recent studies have several important implications. Most importantly, this study provides important estimates in making decisions in the management of this premalignant condition for patients, physicians, and policymakers. Based on these low rates of progression to EAC, should we cease to enroll patients with NDBE in surveillance programs? The answer is no. These data are unable to assess the magnitude of the preventive effect of surveillance on cancer incidence and mortality rates. Without level 1 evidence comparing surveillance to a group not undergoing surveillance, the impact of surveillance on these results remains unclear. However, because the vast majority of patients are cancer-free during long-term follow-up, lengthening of surveillance intervals to possibly every 5 years for NDBE patients should be considered. Cost-effectiveness analysis, including the recent analysis comparing endoscopic eradication therapy for NDBE and LGD with surveillance,13Inadomi J.M. Somsouk M. Madanick R.D. et al.A cost-utility analysis of ablative therapy for Barrett's esophagus.Gastroenterology. 2009; 136: 2101-2114Abstract Full Text Full Text PDF PubMed Scopus (150) Google Scholar have used rates of progression to EAC that are almost twice of what has been reported in these recent studies. Appraisal of current modeling studies using these incidence rates should be performed in future studies. These results add fuel to the controversy whether virtually all BE patients should undergo endoscopic eradication therapies, regardless of presence of dysplasia. Arguments against uniform ablation of all patients with NDBE include lack of efficacy data demonstrating a reduction in the long-term risk of EAC, the large number of patients requiring endoscopic eradication therapies to prevent 1 case of cancer coupled with a very low risk of progression to cancer, the ongoing need for surveillance postablation, recurrence of intestinal metaplasia with the need for maintenance therapies, and the profound economic implications in treating millions of NDBE patients. Even if we assume that ablation of all NDBE patients leads to a reduction in the long-term risk of EAC, benefits in the form of improved survival would be hard to demonstrate as there is no difference in overall mortality rates in patients with NDBE compared with the general population. In fact, in a recent medical position statement, the American Gastroenterological Association has recommended endoscopic eradication therapy for the treatment of patients with confirmed HGD but not for the general population with NDBE.14Spechler S.J. Sharma P. Souza R.F. et al.American Gastroenterological Association medical position statement on the management of Barrett's esophagus.Gastroenterology. 2011; 140: 1084-1091Abstract Full Text Full Text PDF PubMed Scopus (502) Google Scholar This needs to be clarified in a randomized controlled trial comparing endoscopic eradication therapy compared with surveillance in this group of patients. A discussion of implications and controversies surrounding the diagnosis of LGD (variable natural history, significant degree of interobserver agreement even among expert pathologists) and its role in risk stratification is beyond the scope of this editorial. Given the low overall risk of progression of LGD to EAC (rates similar to NDBE), routine endoscopic ablation of all patients with LGD would be difficult to justify. In summary, results from this population-based study highlight the low incidence of cancer in patients with NDBE and LGD; annual incidence of 0.3% and 0.4%, respectively, and the diagnosis of BE has no impact on overall mortality rates. Results from this and other recent studies should temper enthusiasm for wholesale application for endoscopic eradication therapies for patients with NDBE and LGD. The future lies in the creation of a large nation-wide Barrett's consortium that validates these results and provides a comprehensive evaluation of risk factors (clinical characteristics and biomarkers) for progression. This will allow us to accurately risk-stratify patients according to their potential for neoplastic progression using statistical prediction models. These data would then guide in making accurate patient-centered decisions regarding management: surveillance, chemoprevention, or endoscopic eradication therapies. Total Cancer Incidence and Overall Mortality Are Not Increased Among Patients With Barrett's EsophagusClinical Gastroenterology and HepatologyVol. 9Issue 9PreviewBarrett's esophagus (BE) increases risk for esophageal adenocarcinoma, but it is not clear how it affects risk for other cancers or overall mortality. We analyzed data from a population-based cohort of subjects with BE. Full-Text PDF