title: Bacillus Calmette-Guérin failure in patients with non-muscle-invasive urothelial carcinoma of the bladder may be due to the urologist's failure to detect urothelial carcinoma of the upper urinary tract and urethra.
abstract: BACKGROUND
  Various reasons exist for so-called bacillus Calmette-Guérin (BCG) failure in patients with non-muscle-invasive urothelial bladder carcinoma (NMIBC).
  
  
  OBJECTIVE
  To explore whether urothelial carcinoma of the upper urinary tract (UUT) and/or prostatic urethra may be a cause for BCG failure.
  
  
  METHODS
  Retrospective analysis of 110 patients with high-risk NMIBC repeatedly treated with intravesical BCG, diagnosed with disease recurrence, and followed for a median time of 9.1 yr.
  
  
  METHODS
  Two or more intravesical BCG induction courses without maintenance.
  
  
  METHODS
  Primary outcome was pattern of disease recurrence (BCG failure) within the urinary tract categorised into UUT and/or urethral carcinoma (with or without intravesical recurrence), and intravesical recurrence alone. Secondary outcome was survival. Predictors of UUT and/or urethral carcinoma and the effect of pattern of disease recurrence on cancer-specific survival were assessed with multivariable Cox regression analysis adjusting for multiple clinical and tumour characteristics.
  
  
  CONCLUSIONS
  Of the 110 patients, 57 (52%) had UUT and/or urethral carcinoma (with or without intravesical recurrence), and 53 (48%) had intravesical recurrence alone. In patients with UUT and/or urethral carcinoma, bladder carcinoma in situ (Tis) before the first and second BCG course was present in 42 of 57 (74%) and 47 of 57 (82%) patients, respectively. On multivariable analysis, bladder Tis before the first and/or second BCG course was the only independent predictor of UUT and/or urethral carcinoma. Of the 110 patients, 69 (63%) were alive at last follow-up visit, 18 (16%) had died due to metastatic urothelial carcinoma, and 23 (21%) had died of other causes. Pattern of disease recurrence within the urinary tract was not an independent predictor of cancer-specific survival. Main study limitations were retrospective design and limited power for survival analysis.
  
  
  CONCLUSIONS
  In our patients with high-risk NMIBC failing after two or more courses of intravesical BCG, UUT and/or urethral carcinoma was detected in >50% of the cases during follow-up. The vast majority of these patients had bladder Tis before the first and/or second BCG course. In patients experiencing the so-called BCG failure, a diagnostic work-up of UUT and prostatic urethra should always be performed to exclude urothelial carcinoma before additional intravesical therapy or even a radical cystectomy is considered.
authors.affiliation: Department of Urology, University of Bern, Inselspital, Bern, Switzerland.
authors.forename: Gianluca
authors.initials: G
authors.lastname: Giannarini
authors.affiliation: Department of Urology, University of Bern, Inselspital, Bern, Switzerland.
authors.forename: Frédéric D
authors.initials: FD
authors.lastname: Birkhäuser
authors.affiliation: Department of Urology, Kantonsspital Aarau, Aarau, Switzerland.
authors.forename: Franz
authors.initials: F
authors.lastname: Recker
authors.affiliation: Department of Urology, University of Bern, Inselspital, Bern, Switzerland.
authors.forename: George N
authors.initials: GN
authors.lastname: Thalmann
authors.affiliation: Department of Urology, University of Bern, Inselspital, Bern, Switzerland. Electronic address: urology.berne@insel.ch.
authors.forename: Urs E
authors.initials: UE
authors.lastname: Studer
mesh_terms: D000276:Adjuvants, Immunologic / Q000627:therapeutic use*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001500:BCG Vaccine / Q000627:therapeutic use*; D002295:Carcinoma, Transitional Cell / Q000175:diagnosis* / Q000188:drug therapy*; D003951:Diagnostic Errors; D005260:Female; D006801:Humans; D007680:Kidney Neoplasms / Q000175:diagnosis*; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D012189:Retrospective Studies; D017211:Treatment Failure; D014523:Urethral Neoplasms / Q000175:diagnosis*; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy*
chemical_list: D000276:Adjuvants, Immunologic; D001500:BCG Vaccine
keywords: Bacillus Calmette-Guérin; Bladder neoplasms; Carcinoma in situ; Cytology; Follow-up studies; Upper urinary tract; Urothelial carcinoma