Incidence, Characteristics and Implications of Thromboembolic Events in Patients with Muscle Invasive Urothelial Carcinoma of the Bladder Undergoing Neoadjuvant Chemotherapy.
Neoadjuvant chemotherapy and pelvic surgery are significant risk factors for thromboembolic events. Our study objectives were to investigate the timing, incidence and characteristics of thromboembolic events during and after neoadjuvant chemotherapy and subsequent radical cystectomy in patients with muscle invasive bladder cancer.



We performed a multi-institutional retrospective analysis of 761 patients who underwent neoadjuvant chemotherapy and radical cystectomy for muscle invasive bladder cancer from 2002 to 2014. Median followup from diagnosis was 21.4 months (range 3 to 272). Patient characteristics included the Khorana score, and the incidence and timing of thromboembolic events (before vs after radical cystectomy). Survival was calculated using the Kaplan-Meier method. The log rank test and multivariable Cox proportional hazards regression were used to compare survival between patients with vs without thromboembolic events.



The Khorana score indicated an intermediate thromboembolic event risk in 88% of patients. The overall incidence of thromboembolic events in patients undergoing neoadjuvant chemotherapy was 14% with a wide variation of 5% to 32% among institutions. Patients with thromboembolic events were older (67.6 vs 64.6 years, p = 0.02) and received a longer neoadjuvant chemotherapy course (10.9 vs 9.7 weeks, p = 0.01) compared to patients without a thromboembolic event. Of the thromboembolic events 58% developed preoperatively and 72% were symptomatic. On multivariable regression analysis the development of a thromboembolic event was not significantly associated with decreased overall survival. However, pathological stage and a high Khorana score were adverse risk factors for overall survival.



Thromboembolic events are common in patients with muscle invasive bladder cancer who undergo neoadjuvant chemotherapy before and after radical cystectomy. Our results suggest that a prospective trial of thromboembolic event prophylaxis during neoadjuvant chemotherapy is warranted.
McMaster University and Juravinski Hospital, Hamilton, Ontario, Canada.
Wilhelmina C M
WC
Duivenvoorden
University of Southern California-Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, California.
Siamak
S
Daneshmand
Fox Chase Cancer Center, Einstein Health Network and Urologic Institute of Southeastern Pennsylvania, Philadelphia, Pennsylvania.
Daniel
D
Canter
University of Texas Southwestern Medical Center, Dallas, Texas.
Yair
Y
Lotan
Vancouver Prostate Centre, University of British Columbia, Vancouver, British Columbia, Canada.
Peter C
PC
Black
Vancouver Prostate Centre, University of British Columbia, Vancouver, British Columbia, Canada.
Hamidreza
H
Abdi
Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands.
Bas W G
BW
van Rhijn
Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands.
Elisabeth E
EE
Fransen van de Putte
McMaster University and Juravinski Hospital, Hamilton, Ontario, Canada.
Piotr
P
Zareba
Helsinki University Hospital and University of Helsinki, Helsinki, Finland.
Ilmari
I
Koskinen
McGill University, Montreal, Quebec, Canada.
Wassim
W
Kassouf
McGill University, Montreal, Quebec, Canada.
Samer L
SL
Traboulsi
University of Rochester, Rochester, New York.
Janet E
JE
Kukreja
Turku University Hospital and University of Turku, Turku, Finland.
Peter J
PJ
Boström
McMaster University and Juravinski Hospital, Hamilton, Ontario, Canada.
Bobby
B
Shayegan
McMaster University and Juravinski Hospital, Hamilton, Ontario, Canada. Electronic address: pinthusj@hhsc.ca.
Jehonathan H
JH
Pinthus
D000368:Aged; D017024:Chemotherapy, Adjuvant / Q000009:adverse effects* / Q000379:methods; D015653:Cystectomy / Q000009:adverse effects* / Q000379:methods; D005260:Female; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D012189:Retrospective Studies; D016019:Survival Analysis; D013923:Thromboembolism / Q000453:epidemiology* / Q000209:etiology; D001743:Urinary Bladder / Q000473:pathology; D001749:Urinary Bladder Neoplasms / Q000401:mortality / Q000473:pathology / Q000628:therapy*
cystectomy; drug therapy; neoadjuvant therapy; thromboembolism; urinary bladder neoplasms