title: Frequency of tumor recurrence: a strong predictor of stage progression in initially diagnosed nonmuscle invasive bladder cancer.
abstract: OBJECTIVE
  Patients with nonmuscle invasive bladder cancer usually experience multiple instances of tumor recurrence until stage progression occurs. However, it has not yet been fully evaluated whether the timing and/or pattern of tumor recurrence could affect subsequent stage progression. We examined whether the frequency of tumor recurrence provides additional predictive information concerning stage progression.
  
  
  METHODS
  A total of 484 patients with initially diagnosed nonmuscle invasive bladder cancer were identified between 1985 and 2006 at our institution. Median followup was 7.2 years. Frequency of tumor recurrence was analyzed to determine if it affected subsequent stage progression.
  
  
  RESULTS
  Of these patients 40 (8.3%) experienced stage progression during followup. Using Kaplan-Meier analysis subsequent stage progression could be most strongly predicted in patients with a recurrence rate of 1 or more per year during the first 2 years, although similar results were observed for various cutoff periods and recurrence rates. The 10-year progression-free survival rate was 58.0% in patients with a recurrence rate of 1 or more per year and 93.3% in their counterparts (p <0.001). Multivariate analysis demonstrated that the appearance of tumor grade 3 (p = 0.027, risk ratio 2.36), carcinoma in situ (p = 0.045, risk ratio 2.44) and a recurrence rate of 1 or more per year during the first 2 years (p <0.001, risk ratio 7.40) were independent risk factors for subsequent stage progression.
  
  
  CONCLUSIONS
  Frequency of tumor recurrence is a strong predictor of subsequent stage progression in patients initially diagnosed with nonmuscle invasive bladder cancer. More appropriate followup and aggressive treatment due to a higher malignant potential for stage progression might be recommended in patients with a recurrence rate of 1 or more per year during the first 2 years.
authors.affiliation: Department of Urology, Keio University School of Medicine, Tokyo, Japan.
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Tanaka
authors.forename: Eiji
authors.initials: E
authors.lastname: Kikuchi
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Matsumoto
authors.forename: Akira
authors.initials: A
authors.lastname: Miyajima
authors.forename: Ken
authors.initials: K
authors.lastname: Nakagawa
authors.forename: Mototsugu
authors.initials: M
authors.lastname: Oya
mesh_terms: D000283:Administration, Intravesical; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage; D001500:BCG Vaccine / Q000008:administration & dosage; D002295:Carcinoma, Transitional Cell / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology*; D015331:Cohort Studies; D018450:Disease Progression; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D015994:Incidence; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009361:Neoplasm Invasiveness / Q000473:pathology; D009364:Neoplasm Recurrence, Local / Q000453:epidemiology* / Q000473:pathology; D009367:Neoplasm Staging; D011237:Predictive Value of Tests; D011379:Prognosis; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D018570:Risk Assessment; D016019:Survival Analysis; D013997:Time Factors; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology*
chemical_list: D000970:Antineoplastic Agents; D001500:BCG Vaccine