title: Papillary Recurrence of Bladder Cancer at First Evaluation after Induction Bacillus Calmette-Guérin Therapy: Implication for Clinical Trial Design.
abstract: Recurrence with papillary tumor(s) by 3-mo after induction bacillus Calmette-Guérin (BCG) is historically believed to be a poor prognostic indicator in patients with high-risk non-muscle invasive bladder cancer. However, the impact of a clinical Ta (cTa) papillary recurrence at 3 mo after BCG is often debated.
  
  
  
  To evaluate the prognostic implications of cTa papillary recurrence found 3 mo after induction BCG therapy and to evaluate its significance in clinical trial design.
  
  
  
  We reviewed our database of 917 patients who underwent transurethral resection and induction of BCG from 1995 to 2012. Clinical characteristics were compared between 3-mo recurrence stages.
  
  
  
  Transurethral resection of bladder tumor and intravesical therapy.
  
  
  
  Chi-square analysis and Student t test were used to compare clinical characteristics between 3-mo recurrence stages. Kaplan-Meier method was used to determine bladder-preservation time, progression-free survival, and disease-specific survival.
  
  
  
  We identified 84 patients who met the study criteria (66 patients with cTa and 18 patients with clinical T1 [cT1]). The median follow-up for the entire cohort was 74 mo. Of the patients with cTa recurrence, 60 continued with bladder-sparing therapy. Patients with a high-grade cTa recurrence who continued bladder-sparing therapy had a 17% incidence of disease progression and a 62% incidence of recurrence within 1 yr. No patients with low-grade cTa recurrence (n=13) developed disease progression or underwent radical cystectomy. Patients with an initial cTa at diagnosis had a higher 5-yr bladder preservation rate than those with an initial cT1 diagnosis (84% vs 61%; p=0.041). Patients with high-grade cTa recurrence and those with cT1 recurrence had similar outcomes with respect to death rates over the entire follow-up period (11% and 15%, respectively), as well as 5-yr progression-free survival (77% vs 83%). Limitations include using a single institution and a retrospective review.
  
  
  
  Patients with low-grade cTa papillary recurrence 3 mo after induction of BCG can safely continue with bladder-sparing therapy. Patients with high-grade cTa papillary recurrence at that time have risks of recurrence and progression similar to those of patients with cT1 recurrence. These are important factors to consider during clinical trial design.
  
  
  
  Low-grade clinical Ta papillary recurrence following induction of bacillus Calmette-Guérin therapy can be safely managed conservatively, although a high-grade clinical Ta recurrence should be treated similar to a clinical T1 recurrence due to its comparable progression rates.
authors.affiliation: Department of Urology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Chinedu O
authors.initials: CO
authors.lastname: Mmeje
authors.affiliation: Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Charles C
authors.initials: CC
authors.lastname: Guo
authors.affiliation: Department of Urology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Jay B
authors.initials: JB
authors.lastname: Shah
authors.affiliation: Department of Urology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Neema
authors.initials: N
authors.lastname: Navai
authors.affiliation: Department of Urology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: H Barton
authors.initials: HB
authors.lastname: Grossman
authors.affiliation: Department of Urology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Colin P
authors.initials: CP
authors.lastname: Dinney
authors.affiliation: Department of Urology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. Electronic address: akamat@mdanderson.org.
authors.forename: Ashish M
authors.initials: AM
authors.lastname: Kamat
mesh_terms: D000276:Adjuvants, Immunologic / Q000627:therapeutic use; D000283:Administration, Intravesical; D000368:Aged; D001500:BCG Vaccine / Q000008:administration & dosage / Q000009:adverse effects; D002986:Clinical Trials as Topic; D015653:Cystectomy / Q000379:methods / Q000706:statistics & numerical data; D018450:Disease Progression; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009364:Neoplasm Recurrence, Local / Q000175:diagnosis / Q000517:prevention & control; D009367:Neoplasm Staging; D011379:Prognosis; D012107:Research Design; D012189:Retrospective Studies; D001749:Urinary Bladder Neoplasms / Q000175:diagnosis / Q000473:pathology / Q000628:therapy
chemical_list: D000276:Adjuvants, Immunologic; D001500:BCG Vaccine
keywords: Bacillus Calmette-Guérin; Bladder cancer; Clinical outcomes; Non-muscle invasive; Recurrence