title: Long-term follow-up of T1 high-grade bladder cancer after intravesical bacille Calmette-Guérin treatment.
abstract: OBJECTIVE
  To report the long-term results of bacille Calmette-Guérin (BCG) intravesical therapy in relation to disease progression and recurrence in primary T1 high-grade (HG) bladder cancer (BC) confirmed by central pathological review.
  
  
  METHODS
  In all, 136 patients from two university centres (Rotterdam, n = 49; Toronto, n = 87) were diagnosed with primary T1HG BC. One experienced uro-pathologist reviewed all slides, ensuring all cases were indeed HG and that muscle was present in all specimens. Patients were treated with BCG induction (six instillations) after transurethral resection (TUR) of the tumour and followed with cystoscopy and urinary cytology. Predictors for recurrence, progression and survival were assessed with multivariable Cox regression models.
  
  
  RESULTS
  Mean (range) follow-up was 6.5 (0.3-21.6) years. There were no significant differences for recurrence (P = 0.52), progression (P = 0.35) and disease-specific survival (DSS) (P = 0.69) between the two centres. Among the cohort, 47 patients (35%) recurred and 42 (30.9%) progressed with a median time to progression of 2.1 years; 16 (38%) of these progressions occurred ≥ 3 years after the initial BCG course; 22 (16%) patients who progressed died from BC. Overall, 96 (71%) patients had no evidence of disease at the last follow-up. Carcinoma in situ was the only independent predictor for recurrence in multivariate analysis (P = 0.011). No independent predictors were found for progression.
  
  
  CONCLUSIONS
  Conservative treatment with BCG is a valid option in primary T1HG BC. Nevertheless, the aggressive nature of T1HG BC is evident in the fact that 30% progressed, with a high proportion of these progression events occurring ≥ 3 years after BCG. Caution should be exercised when relying on the long-term effects of BCG, and close follow-up of these patients should not be neglected.
authors.affiliation: Department of Surgical Oncology (Division of Urology), Princess Margaret Hospital, Mount Sinai Hospital, University of Toronto, Ontario, Canada.
authors.forename: David M
authors.initials: DM
authors.lastname: Kakiashvili
authors.forename: Bas W G
authors.initials: BW
authors.lastname: van Rhijn
authors.forename: Greg
authors.initials: G
authors.lastname: Trottier
authors.forename: Michael A S
authors.initials: MA
authors.lastname: Jewett
authors.forename: Neil E
authors.initials: NE
authors.lastname: Fleshner
authors.forename: Antonio
authors.initials: A
authors.lastname: Finelli
authors.forename: Julian
authors.initials: J
authors.lastname: Azuero
authors.forename: Chris H
authors.initials: CH
authors.lastname: Bangma
authors.forename: Rati
authors.initials: R
authors.lastname: Vajpeyi
authors.forename: Sultan
authors.initials: S
authors.lastname: Alkhateeb
authors.forename: Sally
authors.initials: S
authors.lastname: Hanna
authors.forename: Alex
authors.initials: A
authors.lastname: Kostynsky
authors.forename: Cynthia
authors.initials: C
authors.lastname: Kuk
authors.forename: Theodorus H
authors.initials: TH
authors.lastname: Van Der Kwast
authors.forename: Alexandre R
authors.initials: AR
authors.lastname: Zlotta
mesh_terms: D000276:Adjuvants, Immunologic / Q000627:therapeutic use*; D000283:Administration, Intravesical; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001500:BCG Vaccine / Q000627:therapeutic use*; D004812:Epidemiologic Methods; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009364:Neoplasm Recurrence, Local / Q000473:pathology*; D016896:Treatment Outcome; D001743:Urinary Bladder / Q000473:pathology*; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy* / Q000473:pathology; D055815:Young Adult
chemical_list: D000276:Adjuvants, Immunologic; D000970:Antineoplastic Agents; D001500:BCG Vaccine