title: Comparative outcomes of primary, recurrent, and progressive high-risk non-muscle-invasive bladder cancer.
abstract: BACKGROUND
  The treatment of high-risk non-muscle-invasive bladder cancer (BCa) is problematic given the variable natural history of the disease. Few reports have compared outcomes for primary high-risk tumours with those that develop following previous BCas (relapses). The latter represent a self-selected cohort, having failed previous treatments.
  
  
  OBJECTIVE
  To compare outcomes in patients with primary, progressive, and recurrent high-risk non-muscle-invasive BCa.
  
  
  METHODS
  We identified all patients with primary and relapsing high-risk BCa tumours at our institution since 1994. Relapses were divided into progressive (previous low- or intermediate-risk disease) and recurrent (previous high-risk disease) cancers.
  
  
  METHODS
  Relationships with outcome analysed using multivariable Cox regression and log-rank analysis.
  
  
  CONCLUSIONS
  We identified 699 primary, 110 progressive, and 494 recurrent high-risk BCa tumours in 809 patients (average follow-up: 59 mo [interquartile range: 6-190]). Muscle invasion occurred most commonly in recurrent (23%) tumours, when compared to progressive (20%) and primary (14.6%) cohorts (log rank p<0.001). Disease-specific mortality (DSM) occurred more frequently in patients with recurrent (25.5%) and progressive (24.6%) tumours compared to primary disease (19.2%; log rank p=0.006). Other-cause mortality was similar in all groups (log rank p=0.57), and overall mortality was highest in the progressive cohort (62%) compared with the recurrent (58%) and primary groups (54%; log rank p<0.001). In multivariable analysis, progression and DSM were predicted by tumour grouping (hazard ratio [HR]: >1.15; p<0.026), stage (HR: >1.30; p<0.001), and patient age and sex (HR: >1.03; p<0.037). Carcinoma in situ was only predictive of outcome in primary tumors. Limitations include retrospective design and limited details regarding bacillus Camille-Guérin use.
  
  
  CONCLUSIONS
  Patients with relapsing, high-risk, BCa tumors have higher progression, DSM, and overall mortality rates than those with primary cancers. The use of bladder-sparing strategies in these patients should approached cautiously. Carcinoma in situ has little predicative role in relapsing, high-risk, BCa tumors.
authors.affiliation: The Academic Urology Unit, University of Sheffield, UK.
authors.forename: Francis
authors.initials: F
authors.lastname: Thomas
authors.forename: Aidan P
authors.initials: AP
authors.lastname: Noon
authors.forename: Naomi
authors.initials: N
authors.lastname: Rubin
authors.forename: John R
authors.initials: JR
authors.lastname: Goepel
authors.forename: James W F
authors.initials: JW
authors.lastname: Catto
mesh_terms: D000283:Administration, Intravesical; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D001500:BCG Vaccine / Q000008:administration & dosage*; D002277:Carcinoma / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D002278:Carcinoma in Situ / Q000401:mortality / Q000473:pathology / Q000628:therapy; D018450:Disease Progression; D018572:Disease-Free Survival; D004739:England / Q000453:epidemiology; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009361:Neoplasm Invasiveness; D009364:Neoplasm Recurrence, Local / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome; D001749:Urinary Bladder Neoplasms / Q000401:mortality / Q000473:pathology / Q000628:therapy*
chemical_list: D000970:Antineoplastic Agents; D001500:BCG Vaccine