title: Multicenter assessment of neoadjuvant chemotherapy for muscle-invasive bladder cancer.
abstract: BACKGROUND
  The efficacy of neoadjuvant chemotherapy (NAC) for muscle-invasive bladder cancer (BCa) was established primarily with methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC), with complete response rates (pT0) as high as 38%. However, because of the comparable efficacy with better tolerability of gemcitabine and cisplatin (GC) in patients with metastatic disease, GC has become the most commonly used regimen in the neoadjuvant setting.
  
  
  OBJECTIVE
  We aimed to assess real-world pathologic response rates to NAC with different regimens in a large, multicenter cohort.
  
  
  METHODS
  Data were collected retrospectively at 19 centers on patients with clinical cT2-4aN0M0 urothelial carcinoma of the bladder who received at least three cycles of NAC, followed by radical cystectomy (RC), between 2000 and 2013.
  
  
  METHODS
  NAC and RC.
  
  
  METHODS
  The primary outcome was pathologic stage at cystectomy. Univariable and multivariable analyses were used to determine factors predictive of pT0N0 and ≤pT1N0 stages.
  
  
  CONCLUSIONS
  Data were collected on 935 patients who met inclusion criteria. GC was used in the majority of the patients (n=602; 64.4%), followed by MVAC (n=183; 19.6%) and other regimens (n=144; 15.4%). The rates of pT0N0 and ≤pT1N0 pathologic response were 22.7% and 40.8%, respectively. The rate of pT0N0 disease for patients receiving GC was 23.9%, compared with 24.5% for MVAC (p=0.2). There was no difference between MVAC and GC in pT0N0 on multivariable analysis (odds ratio: 0.89 [95% confidence interval, 0.61-1.34]; p=0.6).
  
  
  CONCLUSIONS
  Response rates to NAC were lower than those reported in prospective randomized trials, and we did not discern a difference between MVAC and GC. Without any evidence from randomized prospective trials, the best NAC regimen for invasive BCa remains to be determined.
  
  
  RESULTS
  There was no apparent difference in the response rates to the two most common presurgical chemotherapy regimens for patients with bladder cancer.
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authors.affiliation: Department of Genitourinary Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA.
authors.forename: Patrick N
authors.initials: PN
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authors.affiliation: USC/Norris Comprehensive Cancer Center, Institute of Urology, University of Southern California, Los Angeles, CA, USA; University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Adrian S
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authors.lastname: Fairey
authors.affiliation: Department of Urology, The Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands.
authors.forename: Laura S
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authors.lastname: Mertens
authors.affiliation: Department of Urology, MD Anderson Cancer Center, Houston, TX, USA.
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authors.affiliation: Glickman Urological and Kidney Institute, Cleveland Clinic, Cleveland, OH, USA.
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authors.initials: MC
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authors.affiliation: Department of Urology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
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authors.affiliation: Department of Urology, University of Oklahoma College of Medicine, Oklahoma City, OK, USA.
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authors.lastname: Cookson
authors.affiliation: University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Niels-Erik
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authors.affiliation: Department of Urology, The James Buchanan Brady Urological Institute, The Johns Hopkins School of Medicine, Baltimore, MD, USA.
authors.forename: Nilay M
authors.initials: NM
authors.lastname: Gandhi
authors.affiliation: Department of Urology, University of Kansas Medical Center, Kansas City, KS, USA.
authors.forename: Joshua
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authors.lastname: Griffin
authors.affiliation: Department of Urology, University of Michigan Health System, Ann Arbor, MI, USA.
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authors.initials: JS
authors.lastname: Montgomery
authors.affiliation: Department of Urology, Freeman Hospital, Newcastle Upon Tyne, UK.
authors.forename: Nikhil
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authors.affiliation: Department of Medicine, Division of Oncology, University of Washington School of Medicine and Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
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authors.affiliation: Vancouver Prostate Centre, Vancouver, British Columbia, Canada.
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authors.affiliation: Department of Urology, Weill Cornell Medical College, Presbyterian Hospital, New York, NY, USA.
authors.forename: Evanguelos
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authors.lastname: Xylinas
authors.affiliation: Department of Surgery, Exeter Surgical Health Services Research Unit, Royal Devon and Exeter NHS Trust, Exeter, UK.
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authors.initials: NJ
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authors.affiliation: Department of Surgery (Division of Urology), McGill University Health Center, Montreal, Quebec, Canada.
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authors.lastname: Kassouf
authors.affiliation: Department of Urology, University of California at Davis, Davis Medical Center, Sacramento, CA, USA.
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authors.initials: MA
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authors.affiliation: Princess Margaret Hospital, Toronto, Ontario, Canada.
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authors.affiliation: Glickman Urological and Kidney Institute, Cleveland Clinic, Cleveland, OH, USA.
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authors.affiliation: Department of Urology, The Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands.
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authors.lastname: Horenblas
authors.affiliation: Princess Margaret Hospital, Toronto, Ontario, Canada.
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authors.affiliation: Department of Surgery, Exeter Surgical Health Services Research Unit, Royal Devon and Exeter NHS Trust, Exeter, UK.
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authors.affiliation: Department of Urology, Freeman Hospital, Newcastle Upon Tyne, UK; Department of Surgery, Exeter Surgical Health Services Research Unit, Royal Devon and Exeter NHS Trust, Exeter, UK.
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authors.affiliation: Department of Urology, Weill Cornell Medical College, Presbyterian Hospital, New York, NY, USA; Department of Urology, Medical University of Vienna, Vienna General Hospital, Vienna, Austria.
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authors.initials: SF
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authors.affiliation: Department of Urology, Freeman Hospital, Newcastle Upon Tyne, UK.
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authors.affiliation: Department of Urology, University of Michigan Health System, Ann Arbor, MI, USA.
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authors.affiliation: Department of Urology, University of Kansas Medical Center, Kansas City, KS, USA.
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authors.affiliation: Department of Urology, The James Buchanan Brady Urological Institute, The Johns Hopkins School of Medicine, Baltimore, MD, USA.
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authors.affiliation: Department of Urology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
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authors.affiliation: Department of Genitourinary Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA.
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mesh_terms: D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D017024:Chemotherapy, Adjuvant; D002945:Cisplatin / Q000627:therapeutic use; D015653:Cystectomy; D003841:Deoxycytidine / Q000031:analogs & derivatives / Q000627:therapeutic use; D004317:Doxorubicin / Q000627:therapeutic use; D005060:Europe; D005260:Female; D006801:Humans; D008297:Male; D008727:Methotrexate / Q000627:therapeutic use; D008875:Middle Aged; D015999:Multivariate Analysis; D020360:Neoadjuvant Therapy / Q000009:adverse effects; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D009656:North America; D016017:Odds Ratio; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D013997:Time Factors; D016896:Treatment Outcome; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery; D014747:Vinblastine / Q000627:therapeutic use; D000093542:Gemcitabine
chemical_list: D003841:Deoxycytidine; D014747:Vinblastine; D004317:Doxorubicin; D002945:Cisplatin; D008727:Methotrexate; D000093542:Gemcitabine
keywords: Complete pathologic response; Cystectomy; GC; MVAC; Neoadjuvant chemotherapy; Partial pathologic response; Urothelial cancer