title: Should all patients with non-muscle-invasive bladder cancer receive early intravesical chemotherapy after transurethral resection? The results of a prospective randomised multicentre study.
abstract: BACKGROUND
  To decrease recurrences in non-muscle-invasive bladder cancer (NMIBC), the European Association of Urology (EAU) guidelines recommend immediate, intravesical chemotherapy after transurethral resection (TUR) for all patients with Ta/T1 tumours.
  
  
  OBJECTIVE
  To study the benefits of a single, early, intravesical instillation of epirubicin after TUR in patients with low- to intermediate-risk NMIBC.
  
  
  METHODS
  In this prospective randomised multicentre trial, 305 patients with primary as well as recurrent low- to intermediate-risk (Ta/T1, G1/G2) tumours were enrolled between 1997 and 2004. Patients were randomly allocated to receive 80 mg of epirubicin in 50 ml of saline intravesically within 24 h of TUR or no further treatment after TUR.
  
  
  METHODS
  The primary end point was time to first recurrence.
  
  
  CONCLUSIONS
  A total of 219 patients remained for analysis after exclusions. The median follow-up time was 3.9 yr. During the study period, 62% (63 of 102) of the patients in the epirubicin group and 77% (90 of 117) in the control group experienced recurrence (p=0.016). In a multivariate model, the hazard ratio (HR) for recurrence was 0.56 (p=0.002) for early instillation of epirubicin versus no treatment. In a subgroup analysis, the treatment had a profound recurrence-reducing effect on patients with primary, solitary tumours, whereas it provided no benefits in patients with recurrent or multiple tumours. Furthermore, patients with a modified European Organisation for Research and Treatment of Cancer (EORTC) risk score of 0-2 with and without single instillation had recurrence rates of 41% and 69%, respectively (p=0.003), whereas the corresponding rates for those with a risk score of > or = 3 were 81% and 85%, respectively (p=0.35).
  
  
  CONCLUSIONS
  A single, early instillation of epirubicin after TUR for NMIBC reduces the likelihood of tumour recurrence; however, the benefit seems to be minimal in patients at intermediate or high risk of recurrence. Future trials will determine the value of early instillation in addition to serial instillations in NMIBC.
authors.affiliation: Lund University Hospital, Lund, Sweden. Sgudjonsson@hotmail.com
authors.forename: Sigurdur
authors.initials: S
authors.lastname: Gudjónsson
authors.forename: Lars
authors.initials: L
authors.lastname: Adell
authors.forename: Fekadu
authors.initials: F
authors.lastname: Merdasa
authors.forename: Ronnie
authors.initials: R
authors.lastname: Olsson
authors.forename: Bruno
authors.initials: B
authors.lastname: Larsson
authors.forename: Thomas
authors.initials: T
authors.lastname: Davidsson
authors.forename: Jonas
authors.initials: J
authors.lastname: Richthoff
authors.forename: Gunnar
authors.initials: G
authors.lastname: Hagberg
authors.forename: Magnus
authors.initials: M
authors.lastname: Grabe
authors.forename: Pär Ola
authors.initials: PO
authors.lastname: Bendahl
authors.forename: Wiking
authors.initials: W
authors.lastname: Månsson
authors.forename: Fredrik
authors.initials: F
authors.lastname: Liedberg
mesh_terms: D000283:Administration, Intravesical; D000368:Aged; D000903:Antibiotics, Antineoplastic / Q000627:therapeutic use*; D003131:Combined Modality Therapy; D015251:Epirubicin / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008297:Male; D009361:Neoplasm Invasiveness; D011182:Postoperative Care; D011446:Prospective Studies; D013997:Time Factors; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy* / Q000601:surgery*; D013520:Urologic Surgical Procedures / Q000379:methods
chemical_list: D000903:Antibiotics, Antineoplastic; D015251:Epirubicin