Ignite Creation Date:
2024-05-06 @ 11:13 AM
Last Modification Date:
2024-10-26 @ 12:42 PM
Study NCT ID:
NCT03461341
Status:
COMPLETED
Last Update Posted:
2020-03-26
First Post:
2018-03-05
Brief Title:
European iNvestigation of SUrveillance After Resection for Esophageal Cancer
Sponsor:
St Jamess Hospital Ireland
Organization:
St Jamess Hospital Ireland
Study Overview
Official Title:
ENSURE European iNvestigation of SUrveillance After Resection for Esophageal Cancer
Status:
COMPLETED
Status Verified Date:
2020-03
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
ENSURE
Brief Summary:
The ENSURE study will comprise two phases
Phase 1 European multicenter survey of surveillance protocols after esophageal cancer surgery
ENSURE questionnaire will be circulated to representatives from participating European countries
Phase 2 European multicenter retrospective observational study of the impact of postoperative surveillance protocols on oncologic outcome and HR-QL
Phase 2 will constitute a retrospective observational study of patients undergoing treatment with curative intent for esophageal cancer at participating Centers from June 2009 to June 2015
Phase 1 European multicenter survey of surveillance protocols after esophageal cancer surgery
ENSURE questionnaire will be circulated to representatives from participating European countries
Phase 2 European multicenter retrospective observational study of the impact of postoperative surveillance protocols on oncologic outcome and HR-QL
Phase 2 will constitute a retrospective observational study of patients undergoing treatment with curative intent for esophageal cancer at participating Centers from June 2009 to June 2015
Detailed Description:
Despite significant improvements in oncologic outcome for patients with esophageal cancer with increased early detection and greater utilization of multimodal protocolsapproximately 50 and 20 patients with locally advanced and localized disease treated with curative intent will develop disease recurrence within 5 years After completion of treatment there is little evidence to guide surveillance strategies and whether routine clinical biochemical radiologic or endoscopic follow-up is associated with improved oncologic outcomes or health-related quality of life HR-QL is unknown This is in contrast to colorectal cancer where meta-analyses demonstrate a significant overall survival OS benefit among patients undergoing intensive surveillance likely driven by a proportion of patients achieving long-term survival following salvage treatments for oligometastatic disease Importantly intensive surveillance in colorectal cancer did not adversely impact HR-QL in survivorship
In esophageal cancer a lack of quality to indicate that aggressive treatment of recurrent disease provided an OS benefit had previously limited the rationale for intensive oncologic surveillance in this cohort However increasingly reports of long-term survival after salvage surgery for recurrent esophageal cancer among patients treated with esophagectomy as a component of initial treatment are emerging For example Depypere et al reported that among the 15 of patients with isolated local recurrence or single solid organ metastasis who were treated surgically 5-year survival from time of recurrence was 50 median 55 months This is in keeping with data from Schipper et al who report 44 and 35 3- and 5-year survival respectively in the minority of patients for whom R0 re-resection of local recurrence was possible Furthermore while meta-analysis now confirms the survival benefit of palliative chemotherapy HR 081 95 CI 071 to 092 and targeted therapy HR 075 95 CI 068 to 084 the independent impact of timing of intervention and disease volume on OS in the setting of recurrent disease is unclear
Indeed no randomized controlled trial has compared oncologic outcomes among cohorts undergoing different surveillance protocols and only two retrospective observational studies have directly addressed this question In a study from Canada Peixoto et al compared survival outcomes among 292 patients with gastroesophageal cancers 58 esophageal and junctional with 23 treated with definitive chemoradiation only undergoing four different surveillance modalities discharge to General Practitioner or Medical Oncology follow-up with either clinical clinical and biochemical or clinical and radiologicendoscopic surveillance There was no difference in recurrence-free or OS according to surveillance strategy on univariable or multivariable analysis However recent data from Sisic et al advise caution in interpretation of the former study Among 587 patients undergoing either high intensity radiologic or standard clinical surveillance after potentially curative treatment for gastric 47 or junctional 53 adenocarcinoma intensive surveillance independently predicted OS on multivariable analysis and was associated with an approximate 5 increase in OS at 3 and 5 years Notably among patients who developed disease recurrence OS was significantly greater median 40 versus 19 months for those with radiologically-detected versus clinical recurrence and for those who underwent metastectomy n 29 5 of total population versus other treatments median 66 versus 25 months similar to previous series Although this likely reflects at least in part inherent differences in disease biology and volume among those who recur symptomatically versus radiologically patients undergoing high intensity surveillance were more likely to have treatment for recurrence with a proportion of these achieving long-term survival n 11 2 of total population Though limited these data indicate that intensive surveillance may provide benefit for the small proportion of patients who may be treated with curative intent for low volume recurrence
Given the limited evidence to support postoperative surveillance protocols in esophageal cancer it is unsurprising that international guidelines also fail to reach consensus on this topic For example the National Comprehensive Cancer Network NCCN recommend regular cross-sectional imaging with computed tomography CT for all patients with locally advanced disease cT2-4 Nany post multimodal therapy and consideration of regular surveillance CT among patients with T1b Nany treated with upfront esophagectomy up to 3 years postoperatively with endoscopic surveillance only in the case of residual Barretts esophagus In contrast European Society for Medical Oncology ESMO guidelines highlight a lack of evidence to support the role of postoperative surveillance protocols to improve oncologic outcomes and determine that follow-up should concentrate on symptoms nutrition and psychological support and neither routine imaging nor endoscopic surveillance is advocated
As indicated in the ESMO and ASGBI surveillance recommendations there are potential additional benefits to postoperative surveillance protocols Routine clinical surveillance may facilitate identification and management of late post treatment morbidity such as anastomotic stricture post thoracotomy pain malabsorption altered appetite and dumping syndrome Furthermore data from the Netherlands indicate that patients exhibit a strong preference for routine imaging surveillance after esophagectomy with 67 preferring imaging even if this approach would not provide a survival benefit19 This is in keeping with UK colorectal cancer data demonstrating that although surveillance is associated with transient anxiety negative test results provide significant reassurance for the majority Interestingly similar to the Dutch data most patients 78 stated that they would value finding out about the presence of recurrence even if there would be no survival benefit This would provide evidence to counter the concern that postoperative surveillance may negatively influence HR-QL either through increased anxiety related to surveillance investigations or earlier diagnosis of otherwise asymptomatic patients with recurrent disease
Examining surveillance practices internationally there is significant variability in the utilization of biochemical radiologic and endoscopic surveillance In Japan a nationwide survey found that high intensity surveillance was common and notably endoscopic surveillance was frequently utilized 85 in contrast to Australia and New Zealand where only 6 of surgeons opted to undertake routine endoscopic surveillance of asymptomatic patients after potentially curative esophagectomy The European Registration of Cancer Care EURECCA Upper Gastrointestinal group included a brief summary of postoperative surveillance protocols for esophagogastric adenocarcinoma among the 10 participating Centers in a recent publication on clinical pathways Importantly this demonstrated clear differences across European Centers in key elements of surveillance such as the routine use of CT in 40 and tumor markers in 40 but did not describe endoscopic surveillance protocols or duration of surveillance while oncologic outcomes according to surveillance intensity were not assessed
Given these major differences in surveillance intensity and modality across Europe with otherwise similar population demographics and treatment pathways we in Europe are uniquely poised to further study the impact of surveillance with respect to oncologic outcome and HR-QL after potentially curative surgery for esophageal cancer Therefore the primary aims of this European collaborative multicenter study are
1 Firstly to characterize differences in postoperative oncologic surveillance protocols across European esophageal cancer centers and
2 To determine the independent impact of high intensity surveillance HIS on disease-specific and overall survival
In esophageal cancer a lack of quality to indicate that aggressive treatment of recurrent disease provided an OS benefit had previously limited the rationale for intensive oncologic surveillance in this cohort However increasingly reports of long-term survival after salvage surgery for recurrent esophageal cancer among patients treated with esophagectomy as a component of initial treatment are emerging For example Depypere et al reported that among the 15 of patients with isolated local recurrence or single solid organ metastasis who were treated surgically 5-year survival from time of recurrence was 50 median 55 months This is in keeping with data from Schipper et al who report 44 and 35 3- and 5-year survival respectively in the minority of patients for whom R0 re-resection of local recurrence was possible Furthermore while meta-analysis now confirms the survival benefit of palliative chemotherapy HR 081 95 CI 071 to 092 and targeted therapy HR 075 95 CI 068 to 084 the independent impact of timing of intervention and disease volume on OS in the setting of recurrent disease is unclear
Indeed no randomized controlled trial has compared oncologic outcomes among cohorts undergoing different surveillance protocols and only two retrospective observational studies have directly addressed this question In a study from Canada Peixoto et al compared survival outcomes among 292 patients with gastroesophageal cancers 58 esophageal and junctional with 23 treated with definitive chemoradiation only undergoing four different surveillance modalities discharge to General Practitioner or Medical Oncology follow-up with either clinical clinical and biochemical or clinical and radiologicendoscopic surveillance There was no difference in recurrence-free or OS according to surveillance strategy on univariable or multivariable analysis However recent data from Sisic et al advise caution in interpretation of the former study Among 587 patients undergoing either high intensity radiologic or standard clinical surveillance after potentially curative treatment for gastric 47 or junctional 53 adenocarcinoma intensive surveillance independently predicted OS on multivariable analysis and was associated with an approximate 5 increase in OS at 3 and 5 years Notably among patients who developed disease recurrence OS was significantly greater median 40 versus 19 months for those with radiologically-detected versus clinical recurrence and for those who underwent metastectomy n 29 5 of total population versus other treatments median 66 versus 25 months similar to previous series Although this likely reflects at least in part inherent differences in disease biology and volume among those who recur symptomatically versus radiologically patients undergoing high intensity surveillance were more likely to have treatment for recurrence with a proportion of these achieving long-term survival n 11 2 of total population Though limited these data indicate that intensive surveillance may provide benefit for the small proportion of patients who may be treated with curative intent for low volume recurrence
Given the limited evidence to support postoperative surveillance protocols in esophageal cancer it is unsurprising that international guidelines also fail to reach consensus on this topic For example the National Comprehensive Cancer Network NCCN recommend regular cross-sectional imaging with computed tomography CT for all patients with locally advanced disease cT2-4 Nany post multimodal therapy and consideration of regular surveillance CT among patients with T1b Nany treated with upfront esophagectomy up to 3 years postoperatively with endoscopic surveillance only in the case of residual Barretts esophagus In contrast European Society for Medical Oncology ESMO guidelines highlight a lack of evidence to support the role of postoperative surveillance protocols to improve oncologic outcomes and determine that follow-up should concentrate on symptoms nutrition and psychological support and neither routine imaging nor endoscopic surveillance is advocated
As indicated in the ESMO and ASGBI surveillance recommendations there are potential additional benefits to postoperative surveillance protocols Routine clinical surveillance may facilitate identification and management of late post treatment morbidity such as anastomotic stricture post thoracotomy pain malabsorption altered appetite and dumping syndrome Furthermore data from the Netherlands indicate that patients exhibit a strong preference for routine imaging surveillance after esophagectomy with 67 preferring imaging even if this approach would not provide a survival benefit19 This is in keeping with UK colorectal cancer data demonstrating that although surveillance is associated with transient anxiety negative test results provide significant reassurance for the majority Interestingly similar to the Dutch data most patients 78 stated that they would value finding out about the presence of recurrence even if there would be no survival benefit This would provide evidence to counter the concern that postoperative surveillance may negatively influence HR-QL either through increased anxiety related to surveillance investigations or earlier diagnosis of otherwise asymptomatic patients with recurrent disease
Examining surveillance practices internationally there is significant variability in the utilization of biochemical radiologic and endoscopic surveillance In Japan a nationwide survey found that high intensity surveillance was common and notably endoscopic surveillance was frequently utilized 85 in contrast to Australia and New Zealand where only 6 of surgeons opted to undertake routine endoscopic surveillance of asymptomatic patients after potentially curative esophagectomy The European Registration of Cancer Care EURECCA Upper Gastrointestinal group included a brief summary of postoperative surveillance protocols for esophagogastric adenocarcinoma among the 10 participating Centers in a recent publication on clinical pathways Importantly this demonstrated clear differences across European Centers in key elements of surveillance such as the routine use of CT in 40 and tumor markers in 40 but did not describe endoscopic surveillance protocols or duration of surveillance while oncologic outcomes according to surveillance intensity were not assessed
Given these major differences in surveillance intensity and modality across Europe with otherwise similar population demographics and treatment pathways we in Europe are uniquely poised to further study the impact of surveillance with respect to oncologic outcome and HR-QL after potentially curative surgery for esophageal cancer Therefore the primary aims of this European collaborative multicenter study are
1 Firstly to characterize differences in postoperative oncologic surveillance protocols across European esophageal cancer centers and
2 To determine the independent impact of high intensity surveillance HIS on disease-specific and overall survival
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None