Title: Randomised control trial of surveillance and no surveillance for patients with Barrett's oesophagus - BOSS (Barrett's Oesophagus Surveillance Study)
Funder: Department of Health and Social Care

Abstract: Cancer of the gullet (oesophageal adenocarcinoma) is the fastest rising cancer in the developed world. Thirty years ago it was a rare malignancy and now there are over 5,000 cases each year in the UK. The most accepted sequence of events is that longstanding stomach acid reflux induces a cancerous change in the lining of the gullet (oesophagus) in susceptible individuals. The change in the cells is termed Barrett's oesophagus. The UK has the highest incidence of oesophageal adenocarcinoma worldwide. In advanced cancer, the prognosis is poor: half of the patients will die within a year. This concern has promoted the development of surveillance programs. Guidelines recommend that patients with Barrett's oesophagus have an endoscopy every 2-3 years to detect changes early when the prognosis is much more favourable. These guidelines acknowledge that the data to support surveillance in patients with Barrett's oesophagus using endoscopy are relatively weak, and the value of surveillance is still subject to considerable debate. There are some observational data to suggest that patients enrolled in surveillance programmes have oesophageal cancer detected at an earlier stage than non surveillance detected cancers and have a better survival. These are very weak data in epidemiological terms. A randomised controlled trial is needed. Surveillance by endoscopy for Barrett's oesophagus is expensive, it commonly causes minor adverse events (1-10%) and 10% of patients reported that it is inconvenient. It causes anxiety and very rarely can result in complications of oesophageal perforation or death (0.03% and 0.001% respectively). It is important to establish the efficacy and cost effectiveness of such an intervention before routinely offering it to patients.

Lay abstract: Barrett's oesophagus is a condition where the lining of the gullet changes to a stomach or intestinal type lining. Patients with Barrett's oesophagus are much more likely to develop oesophageal cancer. Some doctors recommend that patients with this condition have an endoscopy every two to three years where samples are taken to make sure there are no changes in the lining that may become cancerous (Barrett's surveillance). The aim of Barrett's surveillance is to detect cancer early so it is treatable. The problem is that there is no randomised evidence that this approach saves patients lives. We therefore will randomise 2,500 patients with Barrett's oesophagus to have surveillance every two years or no surveillance. Patients will be followed-up over 10 years and death from all causes and oesophageal cancer will be recorded. The trial will be coordinated by the Research and Development Support unit in Gloucestershire with guidance by the Oxford Clinical Trials Office and randomisation will be carried out using computer generated sequences. Patients will be registered with the Office of National Statistics who will notify us if any patients in the trial die and inform us of the cause of death. The sample size will detect a change in the death from oesophageal cancer from 0.98% to 0.65% per year at the 80% power and 5% significance level. We are in a unique position to carry out this trial as our group is already have experience in major national randomised trial in patients with Barrett's oesophagus. We have a substantial experience in this area, and collected a unique group of clinicians and patients to support the trial. We have spent considerable time and resource to ensure that the trial is accepatble to patients and clinicians and faesable within the time scale. It is fully supported by Barrett's patients groups, the Oesophageal Patients Association and the National socety (British Society of Gastroenterology). The cost are minimised by working within national guidelines, that will not be revised without new data informed by this trial.

Research activity codes: 4.4 POPULATION SCREENING
Health categories: CANCER AND NEOPLASMS;ORAL AND GASTROINTESTINAL