Esophageal Adenocarcinoma and Prior Diagnosis of Barrett's Esophagus
Esophageal Adenocarcinoma and Prior Diagnosis of Barrett's Esophagus
Objective Endoscopic surveillance of Barrett's oesophagus (BO) provides an opportunity to detect early stage oesophageal adenocarcinoma (OAC). We sought to determine the proportion of OAC patients with a prior diagnosis of BO on a population basis and to evaluate the influence of a prior diagnosis of BO on survival, taking into account lead and length time biases.
Design A retrospective population-based study of all OAC patients in Northern Ireland between 2003 and 2008. A prior BO diagnosis was determined by linkage to the Northern Ireland BO register. Stage distribution at diagnosis and histological grade were compared between patients with and without a prior BO diagnosis. Overall survival, using Cox models, was compared between patients with and without a prior BO diagnosis. The effect of adjusting the survival differences for histological grade and estimates of lead and length time bias was assessed.
Results There were 716 OAC cases, 52 (7.3%) of whom had a prior BO diagnosis. Patients with a prior BO diagnosis had significantly lower tumour stage (44.2% vs 11.1% had stage 1 or 2 disease; p<0.001), a higher rate of surgical resection (50.0% vs 25.5%; p<0.001) and had a higher proportion of low/intermediate grade tumours (46.2% vs 26.5%; p=0.011). A prior BO diagnosis was associated with significantly better survival (HR for death 0.39; 95% CI 0.27 to 0.58), which was minimally influenced by adjustment for age, sex and tumour grade (adjusted HR 0.44; 95% CI 0.30 to 0.64). Correction for lead time bias attenuated but did not abolish the survival benefit (HR 0.65; 95% CI 0.45 to 0.95) and further adjustment for length time bias had little effect.
Conclusions The proportion of OAC patients with a prior diagnosis of BO is low; however, prior identification of BO is associated with an improvement in survival in OAC patients.
The incidence of oesophageal adenocarcinoma (OAC) is rising. Once diagnosed, OAC has a poor prognosis with a 5-year survival of less than 20%. Attempts to improve survival have focused on the surveillance of Barrett's oesophagus (BO), the precursor to OAC. The rationale for BO surveillance is that detection of early cancer or dysplasia will result in improved patient outcomes through early treatment. The potential impact of endoscopic surveillance of BO on population OAC mortality is constrained by the proportion of OAC patients that have a prior diagnosis of BO, but few population-based studies have examined this proportion. The largest study to date, which was restricted to patients aged 68 years or older, showed that only 8.1% of OAC patients had a prior diagnosis of OAC. Further population-based studies are required to clarify the proportion of OAC patients with a prior diagnosis of BO in order to assess the likely impact of current BO diagnosis and surveillance strategies on OAC outcomes in populations.
Endoscopic surveillance in BO patients is associated with the detection of earlier stage cancers and improved survival. However, survival estimates in OAC patients detected at surveillance are susceptible to both lead time and length time bias. Lead time bias occurs where surveillance detects cancers at an earlier time point in their natural history; the lead time between diagnosis due to surveillance and diagnosis due to symptoms contributes to any survival benefit observed. Length time bias occurs where slower growing, less aggressive tumours are more likely to be detected at surveillance; subsequent survival analysis may show a survival advantage in surveillance-detected patients, which is due to their tumour biology rather than earlier instigation of treatment. It is also possible that tumours arising in patients with a prior BO diagnosis have inherent biological differences that may positively influence survival. Although both lead and length time bias are recognised as important in cancer screening, no previous study has examined the potential influence of these biases on OAC outcomes in patients with and without a prior diagnosis of BO. Assessment of these issues is crucial to understanding the potential benefits of BO diagnosis and surveillance.
Using unique population data sources, we determined the proportion of OAC patients that have a prior diagnosis of BO and examined the potential influences of lead and length time bias, and differences in tumour grade, on survival in OAC patients with and without a prior diagnosis of BO.
Abstract and Introduction
Abstract
Objective Endoscopic surveillance of Barrett's oesophagus (BO) provides an opportunity to detect early stage oesophageal adenocarcinoma (OAC). We sought to determine the proportion of OAC patients with a prior diagnosis of BO on a population basis and to evaluate the influence of a prior diagnosis of BO on survival, taking into account lead and length time biases.
Design A retrospective population-based study of all OAC patients in Northern Ireland between 2003 and 2008. A prior BO diagnosis was determined by linkage to the Northern Ireland BO register. Stage distribution at diagnosis and histological grade were compared between patients with and without a prior BO diagnosis. Overall survival, using Cox models, was compared between patients with and without a prior BO diagnosis. The effect of adjusting the survival differences for histological grade and estimates of lead and length time bias was assessed.
Results There were 716 OAC cases, 52 (7.3%) of whom had a prior BO diagnosis. Patients with a prior BO diagnosis had significantly lower tumour stage (44.2% vs 11.1% had stage 1 or 2 disease; p<0.001), a higher rate of surgical resection (50.0% vs 25.5%; p<0.001) and had a higher proportion of low/intermediate grade tumours (46.2% vs 26.5%; p=0.011). A prior BO diagnosis was associated with significantly better survival (HR for death 0.39; 95% CI 0.27 to 0.58), which was minimally influenced by adjustment for age, sex and tumour grade (adjusted HR 0.44; 95% CI 0.30 to 0.64). Correction for lead time bias attenuated but did not abolish the survival benefit (HR 0.65; 95% CI 0.45 to 0.95) and further adjustment for length time bias had little effect.
Conclusions The proportion of OAC patients with a prior diagnosis of BO is low; however, prior identification of BO is associated with an improvement in survival in OAC patients.
Introduction
The incidence of oesophageal adenocarcinoma (OAC) is rising. Once diagnosed, OAC has a poor prognosis with a 5-year survival of less than 20%. Attempts to improve survival have focused on the surveillance of Barrett's oesophagus (BO), the precursor to OAC. The rationale for BO surveillance is that detection of early cancer or dysplasia will result in improved patient outcomes through early treatment. The potential impact of endoscopic surveillance of BO on population OAC mortality is constrained by the proportion of OAC patients that have a prior diagnosis of BO, but few population-based studies have examined this proportion. The largest study to date, which was restricted to patients aged 68 years or older, showed that only 8.1% of OAC patients had a prior diagnosis of OAC. Further population-based studies are required to clarify the proportion of OAC patients with a prior diagnosis of BO in order to assess the likely impact of current BO diagnosis and surveillance strategies on OAC outcomes in populations.
Endoscopic surveillance in BO patients is associated with the detection of earlier stage cancers and improved survival. However, survival estimates in OAC patients detected at surveillance are susceptible to both lead time and length time bias. Lead time bias occurs where surveillance detects cancers at an earlier time point in their natural history; the lead time between diagnosis due to surveillance and diagnosis due to symptoms contributes to any survival benefit observed. Length time bias occurs where slower growing, less aggressive tumours are more likely to be detected at surveillance; subsequent survival analysis may show a survival advantage in surveillance-detected patients, which is due to their tumour biology rather than earlier instigation of treatment. It is also possible that tumours arising in patients with a prior BO diagnosis have inherent biological differences that may positively influence survival. Although both lead and length time bias are recognised as important in cancer screening, no previous study has examined the potential influence of these biases on OAC outcomes in patients with and without a prior diagnosis of BO. Assessment of these issues is crucial to understanding the potential benefits of BO diagnosis and surveillance.
Using unique population data sources, we determined the proportion of OAC patients that have a prior diagnosis of BO and examined the potential influences of lead and length time bias, and differences in tumour grade, on survival in OAC patients with and without a prior diagnosis of BO.