title: Computed tomographic colonography compared with colonoscopy or barium enema for diagnosis of colorectal cancer in older symptomatic patients: two multicentre randomised trials with economic evaluation (the SIGGAR trials).
abstract: BACKGROUND
  Computed tomographic colonography (CTC) is a relatively new diagnostic test that may be superior to existing alternatives to investigate the large bowel.
  
  
  OBJECTIVE
  To compare the diagnostic efficacy, acceptability, safety and cost-effectiveness of CTC with barium enema (BE) or colonoscopy.
  
  
  METHODS
  Parallel randomised trials: BE compared with CTC and colonoscopy compared with CTC (randomisation 2 : 1, respectively).
  
  
  METHODS
  A total of 21 NHS hospitals.
  
  
  METHODS
  Patients aged ≥ 55 years with symptoms suggestive of colorectal cancer (CRC).
  
  
  METHODS
  CTC, BE and colonoscopy.
  
  
  METHODS
  For the trial of CTC compared with BE, the primary outcome was the detection rate of CRC and large polyps (≥ 10 mm), with the proportion of patients referred for additional colonic investigation as a secondary outcome. For the trial of CTC compared with colonoscopy, the primary outcome was the proportion of patients referred for additional colonic investigation, with the detection rate of CRC and large polyps as a secondary outcome. Secondary outcomes for both trials were miss rates for cancer (via registry data), all-cause mortality, serious adverse events, patient acceptability, extracolonic pathology and cost-effectiveness.
  
  
  RESULTS
  A total of 8484 patients were registered and 5384 were randomised and analysed (BE trial: 2527 BE, 1277 CTC; colonoscopy trial: 1047 colonoscopy, 533 CTC). Detection rates in the BE trial were 7.3% (93/1277) for CTC, compared with 5.6% (141/2527) for BE (p = 0.0390). The difference was due to better detection of large polyps by CTC (3.6% vs. 2.2%; p = 0.0098), with no significant difference for cancer (3.7% vs. 3.4%; p = 0.66). Significantly more patients having CTC underwent additional investigation (23.5% vs. 18.3%; p = 0.0003). At the 3-year follow-up, the miss rate for CRC was 6.7% for CTC (three missed cancers) and 14.1% for BE (12 missed cancers). Significantly more patients randomised to CTC than to colonoscopy underwent additional investigation (30% vs. 8.2%; p < 0.0001). There was no significant difference in detection rates for cancer or large polyps (10.7% for CTC vs. 11.4% for colonoscopy; p = 0.69), with no difference when cancers (p = 0.94) and large polyps (p = 0.53) were analysed separately. At the 3-year follow-up, the miss rate for cancer was nil for colonoscopy and 3.4% for CTC (one missed cancer). Adverse events were uncommon for all procedures. In 1042 of 1748 (59.6%) CTC examinations, at least one extracolonic finding was reported, and this proportion increased with age (p < 0.0001). A total of 149 patients (8.5%) were subsequently investigated, and extracolonic neoplasia was diagnosed in 79 patients (4.5%) and malignancy in 29 (1.7%). In the short term, CTC was significantly more acceptable to patients than BE or colonoscopy. Total costs for CTC and colonoscopy were finely balanced, but CTC was associated with higher health-care costs than BE. The cost per large polyp or cancer detected was £4235 (95% confidence interval £395 to £9656).
  
  
  CONCLUSIONS
  CTC is superior to BE for detection of cancers and large polyps in symptomatic patients. CTC and colonoscopy detect a similar proportion of large polyps and cancers and their costs are also similar. CTC precipitates significantly more additional investigations than either BE or colonoscopy, and evidence-based referral criteria are needed. Further work is recommended to clarify the extent to which patients initially referred for colonoscopy or BE undergo subsequent abdominopelvic imaging, for example by computed tomography, which will have a significant impact on health economic estimates.
  
  
  BACKGROUND
  Current Controlled Trials ISRCTN95152621.
authors.affiliation: Centre for Medical Imaging, University College London, London, UK.
authors.forename: Steve
authors.initials: S
authors.lastname: Halligan
authors.affiliation: Cancer Screening and Prevention Research Group, Department of Surgery and Cancer, Imperial College London, London, UK.
authors.forename: Edward
authors.initials: E
authors.lastname: Dadswell
authors.affiliation: Cancer Screening and Prevention Research Group, Department of Surgery and Cancer, Imperial College London, London, UK.
authors.forename: Kate
authors.initials: K
authors.lastname: Wooldrage
authors.affiliation: Health Behaviour Research Centre, Department of Epidemiology and Public Health, University College London, London, UK.
authors.forename: Jane
authors.initials: J
authors.lastname: Wardle
authors.affiliation: Health Behaviour Research Centre, Department of Epidemiology and Public Health, University College London, London, UK.
authors.forename: Christian
authors.initials: C
authors.lastname: von Wagner
authors.affiliation: School of Health and Population Sciences, University of Birmingham, Birmingham, UK.|Population Evidence and Technologies, University of Warwick, Warwick, UK.
authors.forename: Richard
authors.initials: R
authors.lastname: Lilford
authors.affiliation: School of Health and Population Sciences, University of Birmingham, Birmingham, UK.|Primary Care and Population Sciences, University of Southampton, Southampton, UK.
authors.forename: Guiqing L
authors.initials: GL
authors.lastname: Yao
authors.affiliation: School of Health and Population Sciences, University of Birmingham, Birmingham, UK.
authors.forename: Shihua
authors.initials: S
authors.lastname: Zhu
authors.affiliation: Cancer Screening and Prevention Research Group, Department of Surgery and Cancer, Imperial College London, London, UK.
authors.forename: Wendy
authors.initials: W
authors.lastname: Atkin
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001466:Barium Sulfate / Q000191:economics*; D023881:Colonography, Computed Tomographic / Q000191:economics* / Q000379:methods; D003113:Colonoscopy / Q000191:economics* / Q000379:methods; D015179:Colorectal Neoplasms / Q000175:diagnosis* / Q000000981:diagnostic imaging; D003362:Cost-Benefit Analysis; D055088:Early Detection of Cancer; D004733:Enema / Q000191:economics* / Q000379:methods; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D017060:Patient Satisfaction; D012680:Sensitivity and Specificity; D012812:Sigmoidoscopy; D006113:United Kingdom
chemical_list: D001466:Barium Sulfate