title: Clinical Outcomes of Patients with Histologic Variants of Urothelial Cancer Treated with Trimodality Bladder-sparing Therapy.
abstract: Trimodality bladder-sparing therapy (TMT) is an acceptable treatment for selected patients with muscle-invasive urothelial cancer. Outcomes of TMT in histologic variants remains largely unknown.
  
  
  
  To compare outcomes of pure urothelial carcinoma (PUC) to variant urothelial carcinoma (VUC) after TMT.
  
  
  
  Retrospective study of patients treated with TMT at a single cancer center from 1993 until 2013.
  
  
  
  Kaplan-Meier survival probabilities, and univariate and multivariable Cox regression analysis.
  
  
  
  Of 303 patients treated with TMT, 66 (22%) had VUC. Fifty (76%) had VUC with squamous and/or glandular differentiation and 16 (24%) had other forms. Complete response rate after induction TMT was 83% in PUC and 82% in VUC (p=0.9). The 5-yr and 10-yr disease-specific survival (DSS) was 75% and 67% in PUC versus 64% and 64% in VUC. The 5-yr and 10-yr overall survival (OS) was 61% and 42% in PUC versus 52% and 42% in VUC. On multivariable analysis VUC was not associated with DSS (hazard ratio: 1.3, 95% confidence interval: 0.8-2.2, p=0.3) or OS (hazard ratio: 1.2, 95% confidence interval: 0.8-1.7, p=0.4). Salvage cystectomy rates were similar (log-rank p=0.3). Limitations include retrospective design and restriction to variants of urothelial cancer.
  
  
  
  VUC responded to TMT, and there was no significant difference in complete response, OS, DSS, or salvage cystectomy rates compared with PUC. The presence of VUC should not exclude patients from TMT.
  
  
  
  The response of histologic variants of bladder cancer to bladder-sparing chemoradiation is largely unknown. We compared the outcomes of histologic variants of urothelial cancer to pure urothelial cancer in a large series of patients from a single institution. We found that variant histology does not significantly influence outcomes.
authors.affiliation: Department of Urology, Massachusetts General Hospital. Harvard Medical School, Boston, MA, USA.
authors.forename: Ross E
authors.initials: RE
authors.lastname: Krasnow
authors.affiliation: Department of Radiation Oncology, Massachusetts General Hospital. Harvard Medical School, Boston, MA, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Drumm
authors.affiliation: Department of Radiation Oncology, Massachusetts General Hospital. Harvard Medical School, Boston, MA, USA.
authors.forename: Hannah J
authors.initials: HJ
authors.lastname: Roberts
authors.affiliation: Department of Radiation Oncology, Massachusetts General Hospital. Harvard Medical School, Boston, MA, USA.
authors.forename: Andrzej
authors.initials: A
authors.lastname: Niemierko
authors.affiliation: Department of Pathology, Massachusetts General Hospital. Harvard Medical School, Boston, MA, USA.
authors.forename: Chin-Lee
authors.initials: CL
authors.lastname: Wu
authors.affiliation: Department of Pathology, Massachusetts General Hospital. Harvard Medical School, Boston, MA, USA.
authors.forename: Shulin
authors.initials: S
authors.lastname: Wu
authors.affiliation: Department of Pathology, Massachusetts General Hospital. Harvard Medical School, Boston, MA, USA.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Urology, Massachusetts General Hospital. Harvard Medical School, Boston, MA, USA.
authors.forename: Niall M
authors.initials: NM
authors.lastname: Heney
authors.affiliation: Department of Urology, Massachusetts General Hospital. Harvard Medical School, Boston, MA, USA.
authors.forename: Matthew F
authors.initials: MF
authors.lastname: Wszolek
authors.affiliation: Department of Urology, Massachusetts General Hospital. Harvard Medical School, Boston, MA, USA.
authors.forename: Michael L
authors.initials: ML
authors.lastname: Blute
authors.affiliation: Department of Urology, Massachusetts General Hospital. Harvard Medical School, Boston, MA, USA.
authors.forename: Adam S
authors.initials: AS
authors.lastname: Feldman
authors.affiliation: Division of Hematology and Oncology, Department of Medicine, Massachusetts General Hospital. Harvard Medical School, Boston, MA, USA.
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Lee
authors.affiliation: Department of Radiation Oncology, Massachusetts General Hospital. Harvard Medical School, Boston, MA, USA.
authors.forename: Anthony L
authors.initials: AL
authors.lastname: Zietman
authors.affiliation: Department of Radiation Oncology, Massachusetts General Hospital. Harvard Medical School, Boston, MA, USA.
authors.forename: William U
authors.initials: WU
authors.lastname: Shipley
authors.affiliation: Department of Radiation Oncology, Massachusetts General Hospital. Harvard Medical School, Boston, MA, USA. Electronic address: jefstathiou@partners.org.
authors.forename: Jason A
authors.initials: JA
authors.lastname: Efstathiou
mesh_terms: D000368:Aged; D001900:Boston; D002277:Carcinoma / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D059186:Chemoradiotherapy, Adjuvant / Q000009:adverse effects / Q000401:mortality; D015653:Cystectomy / Q000009:adverse effects / Q000401:mortality; D018450:Disease Progression; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009361:Neoplasm Invasiveness; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome; D001749:Urinary Bladder Neoplasms / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D019459:Urothelium / Q000473:pathology
keywords: Bladder cancer; Chemotherapy; Combined-modality therapy; Cystectomy; Histology; Outcomes; Radiation therapy; Trimodality therapy