title: Prevention of bladder tumours after nephroureterectomy for primary upper urinary tract urothelial carcinoma: a prospective, multicentre, randomised clinical trial of a single postoperative intravesical dose of mitomycin C (the ODMIT-C Trial).
abstract: BACKGROUND
  Standard treatment for upper urinary tract urothelial carcinoma (UUTUC) is nephroureterectomy. Subsequently, around 40% of patients will develop a bladder tumour potentially because of implantation from the primary tumour.
  
  
  OBJECTIVE
  To prevent bladder tumour after nephroureterectomy with a single postoperative dose of intravesical mitomycin C (MMC).
  
  
  METHODS
  A prospective, randomised, nonblinded trial (ODMIT-C: One Dose Mitomycin C) was undertaken in 46 British centres between July 2000 and December 2006. The study recruited 284 patients with no previous or concurrent history of bladder cancer undergoing nephroureterectomy for suspected UUTUC.
  
  
  METHODS
  A single postoperative intravesical dose of MMC (40 mg in 40 ml saline) or standard management on removal of the urinary catheter.
  
  
  METHODS
  Bladder tumour formation was judged by visual appearance at cystoscopy at 3, 6, and 12 mo following nephroureterectomy.
  
  
  CONCLUSIONS
  One hundred forty-four patients were randomised to receive MMC and 140 patients to receive standard care. In the MMC arm, 105 of 144 patients (73%) and 115 of 140 patients (82%) in the standard care arm received their allocated treatment. Thirteen of 105 patients who received MMC and 20 of 115 patients allocated to standard treatment did not complete follow-up. By modified intention-to-treat analysis, 21 of 120 patients (17%) in the MMC arm developed a bladder recurrence in the first year compared to 32 of 119 patients (27%) in the standard treatment arm (p=0.055). By treatment as per protocol analysis, 17 of 105 patients (16%) in the MMC arm and 31 of 115 patients (27%) in the standard treatment arm developed a recurrence (p=0.03). No serious adverse events were reported. A limitation is that histologic proof of recurrence was not required in this trial.
  
  
  CONCLUSIONS
  A single postoperative dose of intravesical MMC appears to reduce the risk of a bladder tumour within the first year following nephroureterectomy for UUTUC. The absolute reduction in risk is 11%, the relative reduction in risk is 40%, and the number needed to treat to prevent one bladder tumour is nine.
authors.affiliation: Urology Centre, Guys Hospital, Guys and St Thomas' NHS Foundation Trust, London, UK. tim.obrien@gstt.nhs.uk
authors.forename: Tim
authors.initials: T
authors.lastname: O'Brien
authors.forename: Eleanor
authors.initials: E
authors.lastname: Ray
authors.forename: Rajinder
authors.initials: R
authors.lastname: Singh
authors.forename: Bola
authors.initials: B
authors.lastname: Coker
authors.forename: Ralph
authors.initials: R
authors.lastname: Beard
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000903:Antibiotics, Antineoplastic / Q000627:therapeutic use*; D002277:Carcinoma / Q000556:secondary / Q000601:surgery*; D005260:Female; D006801:Humans; D007680:Kidney Neoplasms / Q000473:pathology / Q000601:surgery*; D008297:Male; D008875:Middle Aged; D016685:Mitomycin / Q000627:therapeutic use*; D009392:Nephrectomy / Q000379:methods*; D016896:Treatment Outcome; D014513:Ureter / Q000601:surgery; D014516:Ureteral Neoplasms / Q000473:pathology / Q000601:surgery*; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy / Q000517:prevention & control* / Q000556:secondary; D019459:Urothelium / Q000473:pathology
chemical_list: D000903:Antibiotics, Antineoplastic; D016685:Mitomycin