title: The effectiveness of off-protocol adjuvant chemotherapy for patients with urothelial carcinoma of the urinary bladder.
abstract: OBJECTIVE
  The role of adjuvant chemotherapy for patients with high-risk urothelial carcinoma of the bladder (UCB) is not well defined. Here we address the value of adjuvant chemotherapy in patients undergoing radical cystectomy for UCB in an off-protocol routine clinical setting.
  
  
  METHODS
  We collected and analyzed data from 11 centers contributing retrospective cohorts of patients with UCB treated with radical cystectomy without neoadjuvant chemotherapy. Patients were grouped into quintiles based on their risk of disease progression using estimates from a fitted multivariable Cox proportional hazards model. The association of adjuvant chemotherapy with survival was explored across separate quintiles.
  
  
  RESULTS
  The cohort consisted of 3,947 patients, 932 (23.6%) of whom received adjuvant chemotherapy. Adjuvant chemotherapy was independently associated with improved survival (hazard ratio, 0.83; 95% confidence interval, 0.72-0.97%, P = 0.017). However, the effect of adjuvant chemotherapy was significantly modified by the individual's risk of disease progression such that an increasing benefit from adjuvant chemotherapy was seen across higher-risk subgroups (P < 0.001). There was a significant improvement in survival between the treated and nontreated patients in the highest-risk quintile (hazard ratio, 0.75; 95% confidence interval, 0.62-0.90; P = 0.002). This group was characterized by an estimated 32.8% 5-year probability of cancer-specific survival, with 86.6% of patients having both advanced pathologic stage (> or =T(3)) and nodal involvement.
  
  
  CONCLUSIONS
  Adjuvant chemotherapy is associated with a significant improvement in survival for patients treated in an off-protocol clinical setting. Selective administration in patients at the highest risk for disease progression, such as those with advanced pathologic stage and nodal involvement, may optimize the therapeutic benefit of adjuvant chemotherapy.
authors.affiliation: University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Robert S
authors.initials: RS
authors.lastname: Svatek
authors.forename: Shahrokh F
authors.initials: SF
authors.lastname: Shariat
authors.forename: Robert E
authors.initials: RE
authors.lastname: Lasky
authors.forename: Eila C
authors.initials: EC
authors.lastname: Skinner
authors.forename: Giacomo
authors.initials: G
authors.lastname: Novara
authors.forename: Seth P
authors.initials: SP
authors.lastname: Lerner
authors.forename: Yves
authors.initials: Y
authors.lastname: Fradet
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: Bastian
authors.forename: Wassim
authors.initials: W
authors.lastname: Kassouf
authors.forename: Pierre I
authors.initials: PI
authors.lastname: Karakiewicz
authors.forename: Hans-Martin
authors.initials: HM
authors.lastname: Fritsche
authors.forename: Stefan C
authors.initials: SC
authors.lastname: Müller
authors.forename: Jonathan I
authors.initials: JI
authors.lastname: Izawa
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Ficarra
authors.forename: Arthur I
authors.initials: AI
authors.lastname: Sagalowsky
authors.forename: Mark P
authors.initials: MP
authors.lastname: Schoenberg
authors.forename: Arlene O
authors.initials: AO
authors.lastname: Siefker-Radtke
authors.forename: Randall E
authors.initials: RE
authors.lastname: Millikan
authors.forename: Colin P N
authors.initials: CP
authors.lastname: Dinney
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002295:Carcinoma, Transitional Cell / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery; D017024:Chemotherapy, Adjuvant; D003131:Combined Modality Therapy; D015653:Cystectomy / Q000379:methods; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D012189:Retrospective Studies; D016019:Survival Analysis; D016896:Treatment Outcome; D001743:Urinary Bladder / Q000187:drug effects* / Q000473:pathology / Q000601:surgery; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery; D055815:Young Adult