title: The effect of the time interval between diagnosis of muscle-invasive bladder cancer and radical cystectomy on staging and survival: A Netherlands Cancer Registry analysis.
abstract: BACKGROUND
  Data from single-center series suggest that a delay in time to radical cystectomy (RC) more than 3 months after diagnosis of muscle-invasive bladder cancer (MIBC) is associated with pathological upstaging and decreased survival. However, limited data is available from population-based studies. In this study, the effect of delayed RC was assessed in a nationwide cohort.
  
  
  METHODS
  Patients who underwent RC between 2006 and 2010 with primary clinical T2-T4N0M0 urothelial bladder cancer were selected using the Netherlands Cancer Registry database. Data from the Netherlands Cancer Registry was supplemented with data from the Nationwide Network and Registry of Histo- and Cytopathology database in case of incomplete information. The cohort was divided in patients who underwent RC ≤3 months (group I) vs. patients who underwent RC >3 months (group II). Median time from MIBC diagnosis to RC, variables associated with delayed RC >3 and the effect of delayed RC on staging and overall survival (OS) were evaluated in patients who underwent neoadjuvant therapy and patients who did not.
  
  
  RESULTS
  A total of 1,782 patients were included. Median follow-up time was 5.1 years for living patients and 1.3 years for deceased patients. Median time from MIBC diagnosis to RC was 50 days (interquartile range: 27 days) and 93% of patients underwent RC≤3 months. Patients older than 75 years (odds ratio [OR] = 0.50; 95% CI: 0.32-0.77), referred for RC (OR = 0.41; 95% CI: 0.26-0.69), and treated in a university hospital (OR = 0.34; 95% CI: 0.21-0.56) were less likely to undergo RC≤3 months. Pathologic upstaging rate (43.9% vs. 42.1%) and node-positive disease rate (20.2% vs. 21.7%) did not differ for group I and II. Delayed RC>3 months was not associated with decreased OS adjusting for confounding variables (hazard ratio = 1.16; 95% CI: 0.91-1.48; P = 0.25). Median time from MIBC diagnosis to RC in patients that received neoadjuvant therapy (n = 105) was 133 days (interquartile range: 62 days). Adjusting for confounding variables, delayed RC>3 months was not associated with OS (hazard ratio = 0.90; 95% CI: 0.45-1.82).
  
  
  CONCLUSIONS
  The vast majority of patient underwent RC within 3 months after diagnosis of MIBC, as recommended in the European Association of Urology MIBC guideline. Delayed RC for more than 3 months had no adverse effect on staging and survival.
authors.affiliation: Department of Urology, Radboud University Medical Center, Nijmegen, The Netherlands. Electronic address: max.bruins@radboudumc.nl.
authors.forename: Harman Maxim
authors.initials: HM
authors.lastname: Bruins
authors.affiliation: Netherlands Comprehensive Cancer Organisation (IKNL), Utrecht, The Netherlands; Radboud Institute for Health Sciences (RIHS), Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Katja K H
authors.initials: KK
authors.lastname: Aben
authors.affiliation: Department of Urology, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Tom J
authors.initials: TJ
authors.lastname: Arends
authors.affiliation: Department of Urology, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Antoine G
authors.initials: AG
authors.lastname: van der Heijden
authors.affiliation: Department of Urology, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Alfred J
authors.initials: AJ
authors.lastname: Witjes
mesh_terms: D000368:Aged; D015653:Cystectomy / Q000379:methods / Q000401:mortality; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009367:Neoplasm Staging; D009426:Netherlands / Q000453:epidemiology; D015996:Survival Rate; D013997:Time Factors; D016896:Treatment Outcome; D001749:Urinary Bladder Neoplasms / Q000175:diagnosis* / Q000401:mortality / Q000473:pathology / Q000601:surgery*
keywords: Muscle-invasive bladder cancer; Overall survival; Radical cystectomy; Staging