title: Mixed low- and high-grade non-muscle-invasive bladder cancer: a histological subtype with favorable outcome.
abstract: OBJECTIVE
  To determine whether heterogeneity of tumor grade affects the response to Bacillus Calmette-Guérin (BCG) treatment for patients with non-muscle-invasive bladder cancer (NMIBC).
  
  
  METHODS
  Patients with Ta or T1 NMBIC receiving a 6-week induction course of intravesical BCG therapy after transurethral resection were divided according to the tumor grade. Clinical and pathological variables were compared. Advanced intervention-free survival (AIFS), defined as duration of freedom from advanced intervention (including non-BCG intravesical agents or cystectomy) or metastasis, was plotted using Kaplan-Meier methods. The effect of grade on survival duration was assessed by multivariate Cox proportional hazards modeling.
  
  
  RESULTS
  One hundred and fifty-three patients were identified: 17 with mixed low- and high-grade (MG) and 136 with pure high-grade (PHG) NMIBC. Demographic and additional pathologic variables were comparable between groups (p > 0.05). Five-year AIFS was 88.2% for MG patients, compared to 48.5% for PHG patients (p = 0.030 by log-rank test). On multivariate analysis, PHG was an independent risk factor for worse AIFS (HR 4.4, 95% CI 1.1-18.4, p = 0.040). Among patients failing to respond to primary BCG induction, who underwent a secondary induction of BCG with interferon, MG patients had better response than PHG patients (100 vs. 26.3%, p = 0.035).
  
  
  CONCLUSIONS
  Mixed low- and high-grade NMIBC exhibits a significantly better response profile to intravesical BCG therapy compared to PHG NMIBC. The implications of these results are that less aggressive treatment strategies for this unique cancer entity may be needed and that there is a benefit to the reporting of tumor heterogeneity in transurethral resection of bladder tumor specimens.
authors.affiliation: Department of Urology, Herbert Irving Cancer Center, Columbia University College of Physicians and Surgeons, 161 Fort Washington Avenue, Herbert Irving Pavilion 11th Floor, New York, NY, 10032, USA.
authors.forename: Tina
authors.initials: T
authors.lastname: Schubert
authors.forename: Matthew R
authors.initials: MR
authors.lastname: Danzig
authors.forename: Srinath
authors.initials: S
authors.lastname: Kotamarti
authors.forename: Rashed A
authors.initials: RA
authors.lastname: Ghandour
authors.forename: Danny
authors.initials: D
authors.lastname: Lascano
authors.forename: Byron P
authors.initials: BP
authors.lastname: Dubow
authors.forename: G Joel
authors.initials: GJ
authors.lastname: Decastro
authors.forename: Mitchell C
authors.initials: MC
authors.lastname: Benson
authors.forename: James M
authors.initials: JM
authors.lastname: McKiernan
mesh_terms: D000276:Adjuvants, Immunologic / Q000627:therapeutic use*; D000283:Administration, Intravesical; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001500:BCG Vaccine / Q000627:therapeutic use*; D002295:Carcinoma, Transitional Cell / Q000473:pathology / Q000628:therapy*; D015331:Cohort Studies; D015653:Cystectomy; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009130:Muscle, Smooth / Q000473:pathology*; D060787:Neoplasm Grading; D009361:Neoplasm Invasiveness; D011379:Prognosis; D012189:Retrospective Studies; D016896:Treatment Outcome; D001743:Urinary Bladder / Q000473:pathology* / Q000601:surgery; D001749:Urinary Bladder Neoplasms / Q000473:pathology / Q000628:therapy*
chemical_list: D000276:Adjuvants, Immunologic; D001500:BCG Vaccine