title: Cancer of Oesophagus or Gastricus - New Assessment of Technology of Endosonography (COGNATE): report of pragmatic randomised trial.
abstract: BACKGROUND
  Endoscopic ultrasonography is recommended for staging gastro-oesophageal cancers, but has never been evaluated.
  
  
  OBJECTIVE
  COGNATE (Cancer of Oesophagus or Gastricus - New Assessment of Technology of Endosonography) therefore aimed to evaluate whether adding 'endoscopic ultrasound' (EUS) to the usual staging algorithm changes treatment, improves (quality-adjusted) survival, and uses resources cost-effectively.
  
  
  METHODS
  Pragmatic parallel-group trial. Patients with gastro-oesophageal cancer received standard staging algorithms. Multidisciplinary teams chose provisional management plans from endoscopic mucosal resection, immediate surgery, surgery after chemotherapy, or chemotherapy and radiotherapy. We used dynamic randomisation to allocate consenting patients remotely by telephone in equal proportions between EUS and not. Thereafter we recorded changes in management plan, use of health-care resources, and three aspects of participant-reported quality of life: generic [measured by European Quality of Life - 5 Dimensions (EQ-5D)], cancer related [Functional Assessment of Cancer Therapy - General scale (FACT-G)] and condition-specific [FACT - Additional Concerns scale (FACT-AC)]. We followed participants regularly until death or the end of the trial - for between 1 and 4.5 years. We devised a quality assurance programme to maintain standards of endosonographic reporting.
  
  
  METHODS
  Eight British hospitals, of which two - one Scottish teaching hospital and one English district general hospital - contributed 80% of participants; we combined the other six for analysis.
  
  
  METHODS
  Patients were eligible if they had a diagnosis of gastro-oesophageal cancer, had not started treatment, were free of metastatic disease, were fit for surgery (even if not planned) and had American Society of Anesthesiologists and World Health Organization grades of less than 3.
  
  
  METHODS
  Intervention group: standard staging algorithm plus EUS; control group: standard staging algorithm.
  
  
  METHODS
  Primary: quality-adjusted survival. Secondary: survival; health-related quality of life (EQ-5D, FACT-G and FACT-AC scales); changes in management plan; and complete resection rate. Although blinding participants was neither possible nor desirable, those responsible for analysis remained blind until the Trial Steering Committee had reviewed the definitive analysis.
  
  
  RESULTS
  We randomised 223 patients, of whom 213 yielded enough data for primary analysis. EUS improved survival adjusted for generic quality of life with a hazard ratio of 0.705 [95% confidence interval (CI) 0.499 to 0.995], and crude survival with a hazard ratio of 0.706 (95% CI 0.501 to 0.996). The benefits of EUS were significantly greater for those with poor initial quality of life, but did not differ between centres. EUS reduced net use of health-care resources by £2860 (95% 'bootstrapped' CI from -£2200 to £8000). Combining benefits and savings shows that EUS is likely to be cost-effective, with 96% probability of achieving the National Institute for Health and Care Excellence criterion of costing of < £20,000 to gain a QALY. There were no serious adverse reactions attributable to EUS. EUS enhanced the management plan for many participants, increased the proportion of tumours completely resected from 80% (44 out of 55) to 91% (48 out of 53), and improved the survival of those who changed plan; although underpinning the significant differences in outcome, none of these process differences was itself significant.
  
  
  CONCLUSIONS
  Endoscopic ultrasound significantly improves (quality-adjusted) survival, has the potential to reduce health-care resource use (not statistically significant) and is probably cost-effective (with 96% probability). We recommend research into the best time to evaluate new technologies.
  
  
  BACKGROUND
  ISRCTN1444215.
  
  
  BACKGROUND
  This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 17, No. 39. See the HTA programme website for further project information.
authors.affiliation: North Wales Organisation for Randomised Trials in Health (NWORTH), Bangor University, Bangor, UK.
authors.forename: I T
authors.initials: IT
authors.lastname: Russell
authors.forename: R T
authors.initials: RT
authors.lastname: Edwards
authors.forename: A E
authors.initials: AE
authors.lastname: Gliddon
authors.forename: D K
authors.initials: DK
authors.lastname: Ingledew
authors.forename: D
authors.initials: D
authors.lastname: Russell
authors.forename: R
authors.initials: R
authors.lastname: Whitaker
authors.forename: S T
authors.initials: ST
authors.lastname: Yeo
authors.forename: S E
authors.initials: SE
authors.lastname: Attwood
authors.forename: H
authors.initials: H
authors.lastname: Barr
authors.forename: S
authors.initials: S
authors.lastname: Nanthakumaran
authors.forename: K G M
authors.initials: KG
authors.lastname: Park
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003362:Cost-Benefit Analysis; D019160:Endosonography / Q000191:economics; D004739:England / Q000453:epidemiology; D004938:Esophageal Neoplasms / Q000000981:diagnostic imaging* / Q000401:mortality; D005260:Female; D005770:Gastrointestinal Neoplasms / Q000000981:diagnostic imaging*; D006301:Health Services Needs and Demand / Q000706:statistics & numerical data; D006801:Humans; D008297:Male; D008875:Middle Aged; D011594:Psychometrics; D011785:Quality Assurance, Health Care; D011787:Quality of Health Care; D011795:Surveys and Questionnaires; D013673:Technology Assessment, Biomedical / Q000379:methods*