Incidence, Characteristics and Implications of Thromboembolic Events in Patients with Muscle Invasive Urothelial Carcinoma of the Bladder Undergoing Neoadjuvant Chemotherapy

Wilhelmina C M Duivenvoorden, Siamak Daneshmand, Daniel Canter, Yair Lotan, Peter C. Black, Hamidreza Abdi, Bas W G van Rhijn, Elisabeth E. Fransen van de Putte, Piotr Zareba, Ilmari Koskinen, Wassim Kassouf, Samer L. Traboulsi, Janet E. Kukreja, Peter J. Boström, Bobby Shayegan, Jehonathan H. Pinthus

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Purpose 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. Materials and Methods 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. Results 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. Conclusions 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.

Original languageEnglish (US)
Pages (from-to)1627-1633
Number of pages7
JournalJournal of Urology
Volume196
Issue number6
DOIs
StatePublished - Dec 1 2016

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Urinary Bladder
Carcinoma
Drug Therapy
Muscles
Incidence
Cystectomy
Urinary Bladder Neoplasms
Survival
Regression Analysis

Keywords

  • cystectomy
  • drug therapy
  • neoadjuvant therapy
  • thromboembolism
  • urinary bladder neoplasms

ASJC Scopus subject areas

  • Urology

Cite this

Incidence, Characteristics and Implications of Thromboembolic Events in Patients with Muscle Invasive Urothelial Carcinoma of the Bladder Undergoing Neoadjuvant Chemotherapy. / Duivenvoorden, Wilhelmina C M; Daneshmand, Siamak; Canter, Daniel; Lotan, Yair; Black, Peter C.; Abdi, Hamidreza; van Rhijn, Bas W G; Fransen van de Putte, Elisabeth E.; Zareba, Piotr; Koskinen, Ilmari; Kassouf, Wassim; Traboulsi, Samer L.; Kukreja, Janet E.; Boström, Peter J.; Shayegan, Bobby; Pinthus, Jehonathan H.

In: Journal of Urology, Vol. 196, No. 6, 01.12.2016, p. 1627-1633.

Research output: Contribution to journalArticle

Duivenvoorden, WCM, Daneshmand, S, Canter, D, Lotan, Y, Black, PC, Abdi, H, van Rhijn, BWG, Fransen van de Putte, EE, Zareba, P, Koskinen, I, Kassouf, W, Traboulsi, SL, Kukreja, JE, Boström, PJ, Shayegan, B & Pinthus, JH 2016, 'Incidence, Characteristics and Implications of Thromboembolic Events in Patients with Muscle Invasive Urothelial Carcinoma of the Bladder Undergoing Neoadjuvant Chemotherapy', Journal of Urology, vol. 196, no. 6, pp. 1627-1633. https://doi.org/10.1016/j.juro.2016.06.017
Duivenvoorden, Wilhelmina C M ; Daneshmand, Siamak ; Canter, Daniel ; Lotan, Yair ; Black, Peter C. ; Abdi, Hamidreza ; van Rhijn, Bas W G ; Fransen van de Putte, Elisabeth E. ; Zareba, Piotr ; Koskinen, Ilmari ; Kassouf, Wassim ; Traboulsi, Samer L. ; Kukreja, Janet E. ; Boström, Peter J. ; Shayegan, Bobby ; Pinthus, Jehonathan H. / Incidence, Characteristics and Implications of Thromboembolic Events in Patients with Muscle Invasive Urothelial Carcinoma of the Bladder Undergoing Neoadjuvant Chemotherapy. In: Journal of Urology. 2016 ; Vol. 196, No. 6. pp. 1627-1633.
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abstract = "Purpose 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. Materials and Methods 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. Results 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. Conclusions 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.",
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T1 - Incidence, Characteristics and Implications of Thromboembolic Events in Patients with Muscle Invasive Urothelial Carcinoma of the Bladder Undergoing Neoadjuvant Chemotherapy

AU - Duivenvoorden, Wilhelmina C M

AU - Daneshmand, Siamak

AU - Canter, Daniel

AU - Lotan, Yair

AU - Black, Peter C.

AU - Abdi, Hamidreza

AU - van Rhijn, Bas W G

AU - Fransen van de Putte, Elisabeth E.

AU - Zareba, Piotr

AU - Koskinen, Ilmari

AU - Kassouf, Wassim

AU - Traboulsi, Samer L.

AU - Kukreja, Janet E.

AU - Boström, Peter J.

AU - Shayegan, Bobby

AU - Pinthus, Jehonathan H.

PY - 2016/12/1

Y1 - 2016/12/1

N2 - Purpose 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. Materials and Methods 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. Results 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. Conclusions 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.

AB - Purpose 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. Materials and Methods 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. Results 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. Conclusions 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.

KW - cystectomy

KW - drug therapy

KW - neoadjuvant therapy

KW - thromboembolism

KW - urinary bladder neoplasms

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