title: Thromboembolic events in patients with urothelial carcinoma undergoing neoadjuvant chemotherapy and radical cystectomy.
abstract: OBJECTIVE
  Patients receiving cisplatin are at high risk of thromboembolic events (TEEs). The objective of this study was to assess the effect of cisplatin-based neoadjuvant chemotherapy (NCT) on the incidence of perioperative TEEs in patients undergoing radical cystectomy.
  
  
  METHODS
  We analyzed a consecutive sample of 202 patients with urothelial carcinoma treated with radical cystectomy between 2005 and 2013. Data were collected retrospectively by reviewing medical records. Median follow-up was 16.9 months. Events of interest were defined as venous or arterial TEEs occurring from the date of diagnosis to 30 days after surgery. TEE incidence among patients treated with NCT and cystectomy was compared with that among patients treated with cystectomy alone using Fisher exact test and Cox proportional hazards regression. Proportional hazards regression was also used to assess whether TEE is a predictor of cancer progression and survival.
  
  
  RESULTS
  Of 202 patients, 17 (8.4%) developed a TEE, including 8 of 42 (19.1%) treated with NCT and cystectomy and 9 of 160 (5.6%) treated with cystectomy alone (risk ratio = 3.39, 95% CI: 1.39-8.24). After adjustment for observation time, there remained an association between treatment with NCT and risk of TEE (hazard ratio = 2.40; 95% CI: 0.92-6.27; P = 0.07). Overall, 7 events occurred before cystectomy and 10 occurred postoperatively. Among patients treated with NCT, 6 of 8 events occurred before cystectomy. Detection of TEE was clinically significant as preoperative TEE was found to be an independent predictor of progression and cancer-specific mortality (adjusted hazard ratio = 3.91, 95% CI: 1.34-11.45). The main limitations of our study are its retrospective data collection and small absolute number of events.
  
  
  CONCLUSIONS
  TEE occurs commonly in patients with urothelial carcinoma undergoing NCT. Preoperative TEE is an independent predictor of progression and cancer-specific mortality.
authors.affiliation: Division of Urology, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Piotr
authors.initials: P
authors.lastname: Zareba
authors.affiliation: Division of Urology, McMaster University, Hamilton, Ontario, Canada; Juravinski Cancer Centre, Hamilton Health Sciences, Hamilton, Ontario, Canada.
authors.forename: Laurel
authors.initials: L
authors.lastname: Patterson
authors.affiliation: Division of Urology, McMaster University, Hamilton, Ontario, Canada; Juravinski Cancer Centre, Hamilton Health Sciences, Hamilton, Ontario, Canada.
authors.forename: Rishikesh
authors.initials: R
authors.lastname: Pandya
authors.affiliation: Division of Uro-oncology, Department of Surgical Oncology, Princess Margaret Hospital, University of Toronto, Toronto, Ontario, Canda.
authors.forename: David
authors.initials: D
authors.lastname: Margel
authors.affiliation: Juravinski Cancer Centre, Hamilton Health Sciences, Hamilton, Ontario, Canada; Division of Medical Oncology, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Sebastien J
authors.initials: SJ
authors.lastname: Hotte
authors.affiliation: Juravinski Cancer Centre, Hamilton Health Sciences, Hamilton, Ontario, Canada; Division of Medical Oncology, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Som D
authors.initials: SD
authors.lastname: Mukherjee
authors.affiliation: Juravinski Cancer Centre, Hamilton Health Sciences, Hamilton, Ontario, Canada; Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Leelamma
authors.initials: L
authors.lastname: Elavathil
authors.affiliation: Juravinski Cancer Centre, Hamilton Health Sciences, Hamilton, Ontario, Canada; Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Dean
authors.initials: D
authors.lastname: Daya
authors.affiliation: Division of Urology, McMaster University, Hamilton, Ontario, Canada; St. Joseph׳s Healthcare Hamilton, Hamilton, Ontario, Canada.
authors.forename: Bobby
authors.initials: B
authors.lastname: Shayegan
authors.affiliation: Division of Urology, McMaster University, Hamilton, Ontario, Canada; Juravinski Cancer Centre, Hamilton Health Sciences, Hamilton, Ontario, Canada. Electronic address: jehonathan.pinthus@jcc.hhsc.ca.
authors.forename: Jehonathan H
authors.initials: JH
authors.lastname: Pinthus
mesh_terms: D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects*; D002295:Carcinoma, Transitional Cell / Q000188:drug therapy* / Q000401:mortality / Q000601:surgery; D017024:Chemotherapy, Adjuvant / Q000009:adverse effects; D002945:Cisplatin / Q000009:adverse effects*; D003131:Combined Modality Therapy; D015653:Cystectomy; D005260:Female; D006801:Humans; D015994:Incidence; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy / Q000009:adverse effects; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D013923:Thromboembolism / Q000453:epidemiology* / Q000209:etiology; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000601:surgery
chemical_list: D000970:Antineoplastic Agents; D002945:Cisplatin
keywords: Neoadjuvant chemotherapy; Thromboembolism; Urothelial carcinoma