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Endoscopic Eradication Therapy in Barrett’s Esophagus–Related Neoplasia: Setting the Bar Right to Optimize Patient Outcomes

2016; Elsevier BV; Volume: 150; Issue: 3 Linguagem: Inglês

10.1053/j.gastro.2016.01.022

1528-0012

Sachin Wani, Srinadh Komanduri, V. Raman Muthusamy,

Gastric Cancer Management and Outcomes

Phoa KN, Pouw RE, Bisschops R, et al. Multimodality endoscopic eradication for neoplastic Barrett’s oesophagus: results of an European multicenter study (EURO-II). Gut 2015 Mar 2 [Epub ahead of print]Barrett’s esophagus (BE) is a well-established risk factor for esophageal adenocarcinoma (EAC). Despite all the recent advances, this lethal cancer continues to be associated with a poor 5-year survival rate, especially in patients with advanced stages of cancer. Endoscopic eradication therapy in BE patients at highest risk of progression to invasive cancer (high-grade dysplasia (HGD] and mucosal EAC) is a strategy that has been evaluated extensively to minimize cancer risk and reduce the morbidity and mortality associated with this lethal cancer. The effectiveness of endoscopic eradication therapy has been demonstrated in randomized controlled trials (N Engl J Med 2009;360:2277–2288; JAMA 2014;311:1209–1217) and large observational studies (Gut 2008;57:1200–1206; Gastroenterology 2013;145:79–86; Gastroenterology 2013;145:87–95; Gastroenterology 2013;145:96–104; Gastroenterology 2011;141:460–468). In addition, data from population-based studies have reported comparable outcomes in patients undergoing endoscopic eradication therapy compared to esophagectomy for management of BE-related HGD and mucosal cancer (Gastrointest Endosc 2014;79:224–232). Finally, this practice has now been endorsed by GI societal guidelines (Gastroenterology 2011;140:1084–1091; Am J Gastroenterol 2015, Gut 2014;63:7–42).In this prospective, multicenter cohort study, Phoa et al evaluated outcomes associated with contemporary endoscopic eradication therapy, which is defined as endoscopic mucosal resection (EMR) of visible lesions followed by radiofrequency ablation (RFA) of the remaining Barrett’s segment, in BE patients with HGD and mucosal EAC (Gut 2015 Mar Epub ahead of print). This study was conducted at 13 European tertiary care centers and included BE patients measuring 2-12 cm in length with HGD or mucosal EAC on 2 separate endoscopies (<6 months before inclusion) confirmed histologically by a central expert pathology review. The treatment protocol involved EMR of all visible lesions and the maximum extent of resection was limited to 2 cm in length and 50% of the circumference. This cohort excluded patients with positive deep resection margins, invasion beyond superficial submucosa (T1sm1), poorly or undifferentiated cancer, and lymphovascular invasion. Patients with persistent visible lesions or cancer during the 2 mapping endoscopies and those with esophageal strictures were excluded. Patients were then treated with RFA every 3 months until visual eradication of BE was achieved (maximum of 5 ablation sessions, 2 circumferential and 3 focal ablations). Any residual persistent BE was treated with single EMR or ≤2 sessions with argon plasma coagulation. Histologic assessment for complete eradication of intestinal metaplasia (IM) was performed by biopsies obtained from the gastric cardia (biopsies obtained <5 mm distal to the neosquamocolumnar junction) and from every 2 cm of the original BE segment. After achieving complete eradication of IM, surveillance endoscopy was repeated at 6 months and then yearly thereafter.A total of 132 patients were included in the final analysis with a median BE length Prague C (circumferential) 3 M (maximal extent) 6 and the vast majority of patients underwent EMR (90%) before RFA. Based on EMR, mucosal EAC and HGD were noted in 57% and 23% of cases, respectively. After a median of 4 treatment sessions, complete eradication of neoplasia and complete eradication of IM was achieved in 92% (95% CI, 83-93) and 87% (95% CI, 80-92) of cases, respectively, based on an intention-to-treat analysis. EMR was required in a few patients (n = 6) during RFA treatments and 18% of patients required additional EMR or argon plasma coagulation after completing the maximum allowed number of RFA sessions. The cumulative recurrence rate of neoplasia was 4% and the cumulative recurrence rate of IM was 8% during a median of 27 months of follow-up after achieving complete eradication of IM. This study noted the presence of IM at the neosquamocolumnar junction (not defined as a recurrence) in 24% of cases of which repeat IM was documented in only 4% of cases. Finally, this study demonstrates the safety profile of this multimodality approach. Mild to moderate adverse events were noted in 26 patients, with strictures being the most common adverse event (6%). The authors concluded that a multimodality approach (EMR followed by RFA) is safe, effective, and durable at least based on midterm follow-up in BE patients with HGD and mucosal EAC.CommentThis multicenter, prospective European study further solidifies the effectiveness of multimodality endoscopic eradication therapy in the management of patients with BE-related neoplasia (HGD and mucosal EAC). The investigators should be lauded for coordinating and conducting the largest multicenter study of multimodality endoscopic eradication therapy. This was a well-designed study conducted by international experts who are at the forefront of this treatment modality. This study also paves the path for future prospective multicenter cohort studies in this field.The investigators included BE patients with HGD and mucosal EAC and reported complete eradication of neoplasia in 92% and complete eradication of IM in 87% after treatment. First and foremost, it should be clear that the current goal should be complete eradication of IM. Achieving complete eradication of neoplasia is not sufficient given the risk of metachronous neoplasia (seen in 30% of cases post EMR; Gut 2008;57:1200–1206). The impressive results reported in this study are clearly at the higher end of those published previously (complete eradication of neoplasia and IM rates of 77%-98%; Clin Gastroenterol Hepatol 2013;11:1245–1255). In an era of value-based medicine with an emphasis on quality in endoscopy, these data provide fertile ground for standardization of endoscopic eradication therapy in patients with BE-related neoplasia. What are the factors that drive these high eradication rates reported in this study?First, the training and experience of the endoscopist play a major role in outcomes. This study was conducted at expert centers, and all investigators participating in this study received hands-on training at the coordinating site and were then supervised during RFA procedures to ensure adherence to treatment protocol (first 3-4 by the principal investigator). It is unclear how many endoscopists participated in this study and, although not applicable for the experts included in this study, what constituted adequate training, experience, and competence for inclusion in this study or for that matter in the field of endoscopic eradication therapy is unclear. Trained and competent endoscopists need to have the requisite expertise in careful inspection of BE and lesion detection with the use of high-resolution white light endoscopy and optical chromoendoscopy, ablative techniques and EMR, and management of adverse events during and after endoscopic therapy (bleeding, perforation, stricture, and recurrence of IM and neoplasia). There are few data on learning curves and competence in the field of multimodal endoscopic eradication therapy. The UK group showed an improvement in clinical outcomes for BE-related neoplasia patients comparing results between 2 time periods (2008-2010 and 2011-2013). Complete eradication of neoplasia improved from 77% to 92% between these time periods and complete eradication of IM improved from 56% to 83% (the latter results are similar to results reported in the EURO-II trial.) This improvement was attributed to increased EMR rates of visible lesions before RFA and improved lesion recognition (Gut 2015;64:1192–1199). Another study showed that endoscopists more experienced in RFA required fewer treatment sessions to achieve complete eradication of IM, an effect that disappeared after 30 patients had been treated by the practitioner (Gastroenterology 2015;149:890–896). Competence in endoscopic eradication therapy should not be measured by absolute number of cases but by well-defined and validated competency thresholds.Second, as highlighted, the high rate of EMR performed (90%) in this series before RFA is an important factor associated with the high eradication rates reported in this study. This study also highlights the safety of performing EMR for visible lesions detected at one of the RFA sessions. The role of EMR as a staging and therapeutic tool in the management of BE related neoplasia is well-described. This suggests that a very careful endoscopic examination and a low threshold to resect rather than ablate any focal abnormality is critical. The frequent use of EMR increases the likelihood that only flat dysplasia and IM is treated by RFA, which has a limited depth of tissue injury and penetration of 500-700 μ and should not be used to treated nodular disease. In addition, several studies have demonstrated that EMR results in a change in the histopathologic diagnosis of BE-related neoplasia in patients referred for endoscopic eradication therapy. This allows for improved selection of patients for endoscopic eradication therapy (Dig Dis Sci 2013;58:1703–1709). Third, the performance of circumferential RFA at the gastroesophageal junction (the location of most recurrences) at each RFA session, regardless of the presence of visible BE, may have served to improve the durability of the treatment. Finally, the use of an aggressive acid suppression regimen along with strict follow-up including surveillance biopsies may have contributed to these results.This study provides an excellent opportunity to standardize basic definitions in studies evaluating endoscopic eradication therapy and discuss some pertinent controversies. Complete eradication of IM is defined as absence of endoscopically visible BE and all surveillance biopsies demonstrate no IM (although the number of endoscopies required for this definition is not standardized, this is the primary goal of endoscopic eradication therapy). Complete eradication of neoplasia is the absence of dysplasia or cancer on biopsies obtained after completion of endoscopic eradication therapy in the presence or absence of endoscopically visible BE. Durability of endoscopic eradication therapy is defined by the absence of IM on surveillance biopsies and the duration is calculated from the time of complete eradication of IM to the most recent endoscopy. Recurrence of IM/neoplasia is defined by the presence of IM/neoplasia on surveillance biopsies in the presence or absence of endoscopically visible BE after achieving complete eradication of IM. The authors acknowledge that, because this study was conducted at expert tertiary care centers, the generalizability of these results may be limited. It is also suggested that care of BE-related neoplasia needs to centralized and limited to expert/dedicated centers. Although implementing this recommendation in clinical practice would be difficult, clearly defining the basic prerequisites for an expert/dedicated center managing these patients would be desirable. The basic tenet of any center engaging in endoscopic eradication therapy should be the availability of high-resolution white light endoscopy and the ability to perform ablation and EMR. Results of this study highlight a low recurrence rate of IM (8%) and neoplasia (4%) and may also be attributed to the factors highlighted. Variable rates of recurrence have been reported in literature ranging from 4% to 33% and may be related to whether IM at or just below the neosquamocolumnar junction is included in the numerator of patients with recurrences. The investigators make a strong argument for not including IM at or just below the neosquamocolumnar junction as a recurrence (inability to find IM at subsequent endoscopy in 86% of cases, lack of increase in incidence with time, and limited data suggesting low risk of progression). In a recent meta-analysis, we reported that the annual recurrence rate of IM and neoplasia in patients undergoing multimodality therapy was 5.7 and 1.5 per 100 patient-years (Gastroenterology 2015;148:S765–766). The bottom line is that, when recurrences are detected after complete eradication of IM, they occur predominantly within 2 cm of the neosquamocolumnar junction and can be managed endoscopically in most cases. Evidence-based recommendations are required with regard to surveillance endoscopic and biopsy protocols.Going forward, quality metrics are sorely needed to guide and assess endoscopists performing endoscopic eradication therapy to achieve patient and procedural outcomes similar to the present study. On the road to achieving such utopia, we must first start with the foundation and identification of the key steps that can be standardized and quality metrics that can tracked and measured by all. These metrics should emphasize proper patient assessment and selection for endoscopic eradication therapy, documentation of the necessary endoscopic skills and equipment needed to perform these treatments, careful endoscopic inspection and appropriate use of resection/ablation modalities, documentation and tracking of rates of complete eradication of neoplasia and complete eradication of IM, and long-term follow-up after treatment to assess durability and track adverse events. Most importantly, if such metrics can be validated, they may serve to self-select those endoscopists best suited to perform endoscopic eradication therapy to a more limited number of centers of excellence, as suggested by the authors. Such a development may facilitate achievement of the ultimate goal: a reduction in the incidence, morbidity, and mortality associated with EAC. Phoa KN, Pouw RE, Bisschops R, et al. Multimodality endoscopic eradication for neoplastic Barrett’s oesophagus: results of an European multicenter study (EURO-II). Gut 2015 Mar 2 [Epub ahead of print] Barrett’s esophagus (BE) is a well-established risk factor for esophageal adenocarcinoma (EAC). Despite all the recent advances, this lethal cancer continues to be associated with a poor 5-year survival rate, especially in patients with advanced stages of cancer. Endoscopic eradication therapy in BE patients at highest risk of progression to invasive cancer (high-grade dysplasia (HGD] and mucosal EAC) is a strategy that has been evaluated extensively to minimize cancer risk and reduce the morbidity and mortality associated with this lethal cancer. The effectiveness of endoscopic eradication therapy has been demonstrated in randomized controlled trials (N Engl J Med 2009;360:2277–2288; JAMA 2014;311:1209–1217) and large observational studies (Gut 2008;57:1200–1206; Gastroenterology 2013;145:79–86; Gastroenterology 2013;145:87–95; Gastroenterology 2013;145:96–104; Gastroenterology 2011;141:460–468). In addition, data from population-based studies have reported comparable outcomes in patients undergoing endoscopic eradication therapy compared to esophagectomy for management of BE-related HGD and mucosal cancer (Gastrointest Endosc 2014;79:224–232). Finally, this practice has now been endorsed by GI societal guidelines (Gastroenterology 2011;140:1084–1091; Am J Gastroenterol 2015, Gut 2014;63:7–42). In this prospective, multicenter cohort study, Phoa et al evaluated outcomes associated with contemporary endoscopic eradication therapy, which is defined as endoscopic mucosal resection (EMR) of visible lesions followed by radiofrequency ablation (RFA) of the remaining Barrett’s segment, in BE patients with HGD and mucosal EAC (Gut 2015 Mar Epub ahead of print). This study was conducted at 13 European tertiary care centers and included BE patients measuring 2-12 cm in length with HGD or mucosal EAC on 2 separate endoscopies (<6 months before inclusion) confirmed histologically by a central expert pathology review. The treatment protocol involved EMR of all visible lesions and the maximum extent of resection was limited to 2 cm in length and 50% of the circumference. This cohort excluded patients with positive deep resection margins, invasion beyond superficial submucosa (T1sm1), poorly or undifferentiated cancer, and lymphovascular invasion. Patients with persistent visible lesions or cancer during the 2 mapping endoscopies and those with esophageal strictures were excluded. Patients were then treated with RFA every 3 months until visual eradication of BE was achieved (maximum of 5 ablation sessions, 2 circumferential and 3 focal ablations). Any residual persistent BE was treated with single EMR or ≤2 sessions with argon plasma coagulation. Histologic assessment for complete eradication of intestinal metaplasia (IM) was performed by biopsies obtained from the gastric cardia (biopsies obtained <5 mm distal to the neosquamocolumnar junction) and from every 2 cm of the original BE segment. After achieving complete eradication of IM, surveillance endoscopy was repeated at 6 months and then yearly thereafter. A total of 132 patients were included in the final analysis with a median BE length Prague C (circumferential) 3 M (maximal extent) 6 and the vast majority of patients underwent EMR (90%) before RFA. Based on EMR, mucosal EAC and HGD were noted in 57% and 23% of cases, respectively. After a median of 4 treatment sessions, complete eradication of neoplasia and complete eradication of IM was achieved in 92% (95% CI, 83-93) and 87% (95% CI, 80-92) of cases, respectively, based on an intention-to-treat analysis. EMR was required in a few patients (n = 6) during RFA treatments and 18% of patients required additional EMR or argon plasma coagulation after completing the maximum allowed number of RFA sessions. The cumulative recurrence rate of neoplasia was 4% and the cumulative recurrence rate of IM was 8% during a median of 27 months of follow-up after achieving complete eradication of IM. This study noted the presence of IM at the neosquamocolumnar junction (not defined as a recurrence) in 24% of cases of which repeat IM was documented in only 4% of cases. Finally, this study demonstrates the safety profile of this multimodality approach. Mild to moderate adverse events were noted in 26 patients, with strictures being the most common adverse event (6%). The authors concluded that a multimodality approach (EMR followed by RFA) is safe, effective, and durable at least based on midterm follow-up in BE patients with HGD and mucosal EAC. CommentThis multicenter, prospective European study further solidifies the effectiveness of multimodality endoscopic eradication therapy in the management of patients with BE-related neoplasia (HGD and mucosal EAC). The investigators should be lauded for coordinating and conducting the largest multicenter study of multimodality endoscopic eradication therapy. This was a well-designed study conducted by international experts who are at the forefront of this treatment modality. This study also paves the path for future prospective multicenter cohort studies in this field.The investigators included BE patients with HGD and mucosal EAC and reported complete eradication of neoplasia in 92% and complete eradication of IM in 87% after treatment. First and foremost, it should be clear that the current goal should be complete eradication of IM. Achieving complete eradication of neoplasia is not sufficient given the risk of metachronous neoplasia (seen in 30% of cases post EMR; Gut 2008;57:1200–1206). The impressive results reported in this study are clearly at the higher end of those published previously (complete eradication of neoplasia and IM rates of 77%-98%; Clin Gastroenterol Hepatol 2013;11:1245–1255). In an era of value-based medicine with an emphasis on quality in endoscopy, these data provide fertile ground for standardization of endoscopic eradication therapy in patients with BE-related neoplasia. What are the factors that drive these high eradication rates reported in this study?First, the training and experience of the endoscopist play a major role in outcomes. This study was conducted at expert centers, and all investigators participating in this study received hands-on training at the coordinating site and were then supervised during RFA procedures to ensure adherence to treatment protocol (first 3-4 by the principal investigator). It is unclear how many endoscopists participated in this study and, although not applicable for the experts included in this study, what constituted adequate training, experience, and competence for inclusion in this study or for that matter in the field of endoscopic eradication therapy is unclear. Trained and competent endoscopists need to have the requisite expertise in careful inspection of BE and lesion detection with the use of high-resolution white light endoscopy and optical chromoendoscopy, ablative techniques and EMR, and management of adverse events during and after endoscopic therapy (bleeding, perforation, stricture, and recurrence of IM and neoplasia). There are few data on learning curves and competence in the field of multimodal endoscopic eradication therapy. The UK group showed an improvement in clinical outcomes for BE-related neoplasia patients comparing results between 2 time periods (2008-2010 and 2011-2013). Complete eradication of neoplasia improved from 77% to 92% between these time periods and complete eradication of IM improved from 56% to 83% (the latter results are similar to results reported in the EURO-II trial.) This improvement was attributed to increased EMR rates of visible lesions before RFA and improved lesion recognition (Gut 2015;64:1192–1199). Another study showed that endoscopists more experienced in RFA required fewer treatment sessions to achieve complete eradication of IM, an effect that disappeared after 30 patients had been treated by the practitioner (Gastroenterology 2015;149:890–896). Competence in endoscopic eradication therapy should not be measured by absolute number of cases but by well-defined and validated competency thresholds.Second, as highlighted, the high rate of EMR performed (90%) in this series before RFA is an important factor associated with the high eradication rates reported in this study. This study also highlights the safety of performing EMR for visible lesions detected at one of the RFA sessions. The role of EMR as a staging and therapeutic tool in the management of BE related neoplasia is well-described. This suggests that a very careful endoscopic examination and a low threshold to resect rather than ablate any focal abnormality is critical. The frequent use of EMR increases the likelihood that only flat dysplasia and IM is treated by RFA, which has a limited depth of tissue injury and penetration of 500-700 μ and should not be used to treated nodular disease. In addition, several studies have demonstrated that EMR results in a change in the histopathologic diagnosis of BE-related neoplasia in patients referred for endoscopic eradication therapy. This allows for improved selection of patients for endoscopic eradication therapy (Dig Dis Sci 2013;58:1703–1709). Third, the performance of circumferential RFA at the gastroesophageal junction (the location of most recurrences) at each RFA session, regardless of the presence of visible BE, may have served to improve the durability of the treatment. Finally, the use of an aggressive acid suppression regimen along with strict follow-up including surveillance biopsies may have contributed to these results.This study provides an excellent opportunity to standardize basic definitions in studies evaluating endoscopic eradication therapy and discuss some pertinent controversies. Complete eradication of IM is defined as absence of endoscopically visible BE and all surveillance biopsies demonstrate no IM (although the number of endoscopies required for this definition is not standardized, this is the primary goal of endoscopic eradication therapy). Complete eradication of neoplasia is the absence of dysplasia or cancer on biopsies obtained after completion of endoscopic eradication therapy in the presence or absence of endoscopically visible BE. Durability of endoscopic eradication therapy is defined by the absence of IM on surveillance biopsies and the duration is calculated from the time of complete eradication of IM to the most recent endoscopy. Recurrence of IM/neoplasia is defined by the presence of IM/neoplasia on surveillance biopsies in the presence or absence of endoscopically visible BE after achieving complete eradication of IM. The authors acknowledge that, because this study was conducted at expert tertiary care centers, the generalizability of these results may be limited. It is also suggested that care of BE-related neoplasia needs to centralized and limited to expert/dedicated centers. Although implementing this recommendation in clinical practice would be difficult, clearly defining the basic prerequisites for an expert/dedicated center managing these patients would be desirable. The basic tenet of any center engaging in endoscopic eradication therapy should be the availability of high-resolution white light endoscopy and the ability to perform ablation and EMR. Results of this study highlight a low recurrence rate of IM (8%) and neoplasia (4%) and may also be attributed to the factors highlighted. Variable rates of recurrence have been reported in literature ranging from 4% to 33% and may be related to whether IM at or just below the neosquamocolumnar junction is included in the numerator of patients with recurrences. The investigators make a strong argument for not including IM at or just below the neosquamocolumnar junction as a recurrence (inability to find IM at subsequent endoscopy in 86% of cases, lack of increase in incidence with time, and limited data suggesting low risk of progression). In a recent meta-analysis, we reported that the annual recurrence rate of IM and neoplasia in patients undergoing multimodality therapy was 5.7 and 1.5 per 100 patient-years (Gastroenterology 2015;148:S765–766). The bottom line is that, when recurrences are detected after complete eradication of IM, they occur predominantly within 2 cm of the neosquamocolumnar junction and can be managed endoscopically in most cases. Evidence-based recommendations are required with regard to surveillance endoscopic and biopsy protocols.Going forward, quality metrics are sorely needed to guide and assess endoscopists performing endoscopic eradication therapy to achieve patient and procedural outcomes similar to the present study. On the road to achieving such utopia, we must first start with the foundation and identification of the key steps that can be standardized and quality metrics that can tracked and measured by all. These metrics should emphasize proper patient assessment and selection for endoscopic eradication therapy, documentation of the necessary endoscopic skills and equipment needed to perform these treatments, careful endoscopic inspection and appropriate use of resection/ablation modalities, documentation and tracking of rates of complete eradication of neoplasia and complete eradication of IM, and long-term follow-up after treatment to assess durability and track adverse events. Most importantly, if such metrics can be validated, they may serve to self-select those endoscopists best suited to perform endoscopic eradication therapy to a more limited number of centers of excellence, as suggested by the authors. Such a development may facilitate achievement of the ultimate goal: a reduction in the incidence, morbidity, and mortality associated with EAC. This multicenter, prospective European study further solidifies the effectiveness of multimodality endoscopic eradication therapy in the management of patients with BE-related neoplasia (HGD and mucosal EAC). The investigators should be lauded for coordinating and conducting the largest multicenter study of multimodality endoscopic eradication therapy. This was a well-designed study conducted by international experts who are at the forefront of this treatment modality. This study also paves the path for future prospective multicenter cohort studies in this field. The investigators included BE patients with HGD and mucosal EAC and reported complete eradication of neoplasia in 92% and complete eradication of IM in 87% after treatment. First and foremost, it should be clear that the current goal should be complete eradication of IM. Achieving complete eradication of neoplasia is not sufficient given the risk of metachronous neoplasia (seen in 30% of cases post EMR; Gut 2008;57:1200–1206). The impressive results reported in this study are clearly at the higher end of those published previously (complete eradication of neoplasia and IM rates of 77%-98%; Clin Gastroenterol Hepatol 2013;11:1245–1255). In an era of value-based medicine with an emphasis on quality in endoscopy, these data provide fertile ground for standardization of endoscopic eradication therapy in patients with BE-related neoplasia. What are the factors that drive these high eradication rates reported in this study? First, the training and experience of the endoscopist play a major role in outcomes. This study was conducted at expert centers, and all investigators participating in this study received hands-on training at the coordinating site and were then supervised during RFA procedures to ensure adherence to treatment protocol (first 3-4 by the principal investigator). It is unclear how many endoscopists participated in this study and, although not applicable for the experts included in this study, what constituted adequate training, experience, and competence for inclusion in this study or for that matter in the field of endoscopic eradication therapy is unclear. Trained and competent endoscopists need to have the requisite expertise in careful inspection of BE and lesion detection with the use of high-resolution white light endoscopy and optical chromoendoscopy, ablative techniques and EMR, and management of adverse events during and after endoscopic therapy (bleeding, perforation, stricture, and recurrence of IM and neoplasia). There are few data on learning curves and competence in the field of multimodal endoscopic eradication therapy. The UK group showed an improvement in clinical outcomes for BE-related neoplasia patients comparing results between 2 time periods (2008-2010 and 2011-2013). Complete eradication of neoplasia improved from 77% to 92% between these time periods and complete eradication of IM improved from 56% to 83% (the latter results are similar to results reported in the EURO-II trial.) This improvement was attributed to increased EMR rates of visible lesions before RFA and improved lesion recognition (Gut 2015;64:1192–1199). Another study showed that endoscopists more experienced in RFA required fewer treatment sessions to achieve complete eradication of IM, an effect that disappeared after 30 patients had been treated by the practitioner (Gastroenterology 2015;149:890–896). Competence in endoscopic eradication therapy should not be measured by absolute number of cases but by well-defined and validated competency thresholds. Second, as highlighted, the high rate of EMR performed (90%) in this series before RFA is an important factor associated with the high eradication rates reported in this study. This study also highlights the safety of performing EMR for visible lesions detected at one of the RFA sessions. The role of EMR as a staging and therapeutic tool in the management of BE related neoplasia is well-described. This suggests that a very careful endoscopic examination and a low threshold to resect rather than ablate any focal abnormality is critical. The frequent use of EMR increases the likelihood that only flat dysplasia and IM is treated by RFA, which has a limited depth of tissue injury and penetration of 500-700 μ and should not be used to treated nodular disease. In addition, several studies have demonstrated that EMR results in a change in the histopathologic diagnosis of BE-related neoplasia in patients referred for endoscopic eradication therapy. This allows for improved selection of patients for endoscopic eradication therapy (Dig Dis Sci 2013;58:1703–1709). Third, the performance of circumferential RFA at the gastroesophageal junction (the location of most recurrences) at each RFA session, regardless of the presence of visible BE, may have served to improve the durability of the treatment. Finally, the use of an aggressive acid suppression regimen along with strict follow-up including surveillance biopsies may have contributed to these results. This study provides an excellent opportunity to standardize basic definitions in studies evaluating endoscopic eradication therapy and discuss some pertinent controversies. Complete eradication of IM is defined as absence of endoscopically visible BE and all surveillance biopsies demonstrate no IM (although the number of endoscopies required for this definition is not standardized, this is the primary goal of endoscopic eradication therapy). Complete eradication of neoplasia is the absence of dysplasia or cancer on biopsies obtained after completion of endoscopic eradication therapy in the presence or absence of endoscopically visible BE. Durability of endoscopic eradication therapy is defined by the absence of IM on surveillance biopsies and the duration is calculated from the time of complete eradication of IM to the most recent endoscopy. Recurrence of IM/neoplasia is defined by the presence of IM/neoplasia on surveillance biopsies in the presence or absence of endoscopically visible BE after achieving complete eradication of IM. The authors acknowledge that, because this study was conducted at expert tertiary care centers, the generalizability of these results may be limited. It is also suggested that care of BE-related neoplasia needs to centralized and limited to expert/dedicated centers. Although implementing this recommendation in clinical practice would be difficult, clearly defining the basic prerequisites for an expert/dedicated center managing these patients would be desirable. The basic tenet of any center engaging in endoscopic eradication therapy should be the availability of high-resolution white light endoscopy and the ability to perform ablation and EMR. Results of this study highlight a low recurrence rate of IM (8%) and neoplasia (4%) and may also be attributed to the factors highlighted. Variable rates of recurrence have been reported in literature ranging from 4% to 33% and may be related to whether IM at or just below the neosquamocolumnar junction is included in the numerator of patients with recurrences. The investigators make a strong argument for not including IM at or just below the neosquamocolumnar junction as a recurrence (inability to find IM at subsequent endoscopy in 86% of cases, lack of increase in incidence with time, and limited data suggesting low risk of progression). In a recent meta-analysis, we reported that the annual recurrence rate of IM and neoplasia in patients undergoing multimodality therapy was 5.7 and 1.5 per 100 patient-years (Gastroenterology 2015;148:S765–766). The bottom line is that, when recurrences are detected after complete eradication of IM, they occur predominantly within 2 cm of the neosquamocolumnar junction and can be managed endoscopically in most cases. Evidence-based recommendations are required with regard to surveillance endoscopic and biopsy protocols. Going forward, quality metrics are sorely needed to guide and assess endoscopists performing endoscopic eradication therapy to achieve patient and procedural outcomes similar to the present study. On the road to achieving such utopia, we must first start with the foundation and identification of the key steps that can be standardized and quality metrics that can tracked and measured by all. These metrics should emphasize proper patient assessment and selection for endoscopic eradication therapy, documentation of the necessary endoscopic skills and equipment needed to perform these treatments, careful endoscopic inspection and appropriate use of resection/ablation modalities, documentation and tracking of rates of complete eradication of neoplasia and complete eradication of IM, and long-term follow-up after treatment to assess durability and track adverse events. Most importantly, if such metrics can be validated, they may serve to self-select those endoscopists best suited to perform endoscopic eradication therapy to a more limited number of centers of excellence, as suggested by the authors. Such a development may facilitate achievement of the ultimate goal: a reduction in the incidence, morbidity, and mortality associated with EAC.