Thromboprophylaxis during neoadjuvant chemotherapy for bladder cancer reduces thromboembolism and bleeding

Luca Antonelli^{1

2}, Pedro David Wendel-Garcia^{3

4}, Manja Deforth³, Luca Afferi¹, Costantino Leonardo², Francesco Esperto⁵, Marco Borghesi^{6

7}, Alessandro Antonelli⁸, Karl Tully⁹, Paolo Umari¹⁰, Simone Albisinni^{11

12}, Andrea Mari¹³, Renate Pichler¹⁴, Francesco Claps¹⁵, Jeremy Yuen-Chun Teoh¹⁶, Mathieu Roumiguié¹⁷, Gerald Bastian Schulz¹⁸, Luca Orecchia¹⁹, Francesco Soria²⁰, Morgan Roupret²¹, Gautier Marcq^{22

23}, Cedric Poyet²⁴, Majed Alrumayyan²⁵, Michael Rink²⁶, Stefania Zamboni²⁷, Maria Riaza Montes²⁸, Steven Okoye²⁹, Riccardo Campi^{30

31}, Wojciech Krajewski³², Laura Mertens³³, Meftun Culpan³⁴, Luke T Lavallée³⁵, Marco Moschini³⁶, Ulrike Held³, Christian Daniel Fankhauser^{1

37}; EAU YAU urothelial carcinoma working group

Affiliations

¹ Department of Urology, Luzerner Kantonsspital, University of Lucerne, Lucerne, Switzerland.
² Department of Urology, Sapienza University of Rome, Rome, Italy.
³ Department of Biostatistics at the Epidemiology, Biostatistics and Prevention Institute, University of Zurich, Zurich, Switzerland.
⁴ Institute of Intensive Care Medicine, University Hospital Zurich, Zurich, Switzerland.
⁵ Department of Urology, Campus Bio-Medico University, Rome, Italy.
⁶ IRCCS Ospedale Policlinico S. Martino, Genoa, Italy.
⁷ Department of Surgical and Diagnostic Integrated Sciences, University of Genoa, Genoa, Italy.
⁸ Department of Urology, Azienda Ospedaliera Universitaria Integrata Verona, Verona, Italy.
⁹ Departement of Urology and Neurourology, Marien Hospital Herne, Ruhr University Bochum, Bochum, Germany.
¹⁰ St. George's University Hospital, London, UK.
¹¹ Urology Unit, Department of Surgical Sciences, Tor Vergata University Hospital, University of Rome Tor Vergata, Rome, Italy.
¹² Service d'Urologie, Hôpital Universitaire de Bruxelles, Université Libre de Bruxelles, Bruxells, Belgium.
¹³ Unit of Oncologic Minimally-Invasive Urology and Andrology - Careggi Hospital, Department of Clinical and Experimental Medicine, University of Florence, Florence, Italy.
¹⁴ Department of Urology, Medical University of Innsbruck, Innsbruck, Austria.
¹⁵ Department of Medicine, Surgery and Health Sciences, Urological Clinic, University of Trieste, Trieste, Italy.
¹⁶ Department of Surgery, S.H. Ho Urology Centre, The Chinese University of Hong Kong, Hong Kong, China.
¹⁷ Department of Urology, CHU-IUCT Toulouse, Toulouse, France.
¹⁸ Department of Urology, LMU Munich, Munich, Germany.
¹⁹ Urology Unit, Policlinico Tor Vergata Foundation, Rome, Italy.
²⁰ Division of Urology, Department of Surgical Sciences, Torino School of Medicine, AOU città della Salute e della Scienza di Torino, Torino, Italy.
²¹ GRC 5 Predictive Onco-Uro, AP-HP, Urology, Pitie-Salpetriere Hospital, Sorbonne University, Paris, France.
²² Urology Department, Claude Huriez Hospital, CHU Lille, Lille, France.
²³ CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, UMR9020-U1277 - CANTHER - Cancer Heterogeneity Plasticity and Resistance to Therapies, University Lille, Lille, France.
²⁴ Department of Urology, University Hospital Zürich, Zürich, Switzerland.
²⁵ Division of Urology, Department of Surgery, Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada.
²⁶ Department of Urology, Marienkrankenhaus Hamburg, Hamburg, Germany.
²⁷ Unit of Urology, Department of Medical and Surgical Specialities, Radiological Science and Public Health, ASST Spedali Civili di Brescia, University of Brescia, Brescia, Italy.
²⁸ Galdakao-Usansolo Hospital, Vizcaya, Spain.
²⁹ Department of Urology, Charité-Universitätsmedizin Berlin, Berlin, Germany.
³⁰ Unit of Urological Robotic Surgery and Renal Transplantation, Careggi Hospital, University of Florence, Florence, Italy.
³¹ Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy.
³² Department of Minimally Invasive and Robotic Urology, Wrocław Medical University, Wrocław, Poland.
³³ Department of Urology, Netherlands Cancer Institute, Amsterdam, Netherlands.
³⁴ Department of Urology, Faculty of Medicine, Istanbul Medeniyet University, Istanbul, Turkey.
³⁵ Division of Urology, Department of Surgery, University of Ottawa and Ottawa Hospital Research Institute, Ottawa, Canada.
³⁶ Department of Urology and Division of Experimental Oncology, Urological Research Institute, Vita-Salute San Raffaele, Milan, Italy.
³⁷ University of Zurich, Zurich, Switzerland.

PMID: 38961717
DOI: 10.1111/bju.16444

Multicenter Study

Thromboprophylaxis during neoadjuvant chemotherapy for bladder cancer reduces thromboembolism and bleeding

Luca Antonelli et al. BJU Int. 2024 Nov.

. 2024 Nov;134(5):781-788.

doi: 10.1111/bju.16444. Epub 2024 Jul 3.

Authors

Affiliations

¹ Department of Urology, Luzerner Kantonsspital, University of Lucerne, Lucerne, Switzerland.
² Department of Urology, Sapienza University of Rome, Rome, Italy.
³ Department of Biostatistics at the Epidemiology, Biostatistics and Prevention Institute, University of Zurich, Zurich, Switzerland.
⁴ Institute of Intensive Care Medicine, University Hospital Zurich, Zurich, Switzerland.
⁵ Department of Urology, Campus Bio-Medico University, Rome, Italy.
⁶ IRCCS Ospedale Policlinico S. Martino, Genoa, Italy.
⁷ Department of Surgical and Diagnostic Integrated Sciences, University of Genoa, Genoa, Italy.
⁸ Department of Urology, Azienda Ospedaliera Universitaria Integrata Verona, Verona, Italy.
⁹ Departement of Urology and Neurourology, Marien Hospital Herne, Ruhr University Bochum, Bochum, Germany.
¹⁰ St. George's University Hospital, London, UK.
¹¹ Urology Unit, Department of Surgical Sciences, Tor Vergata University Hospital, University of Rome Tor Vergata, Rome, Italy.
¹² Service d'Urologie, Hôpital Universitaire de Bruxelles, Université Libre de Bruxelles, Bruxells, Belgium.
¹³ Unit of Oncologic Minimally-Invasive Urology and Andrology - Careggi Hospital, Department of Clinical and Experimental Medicine, University of Florence, Florence, Italy.
¹⁴ Department of Urology, Medical University of Innsbruck, Innsbruck, Austria.
¹⁵ Department of Medicine, Surgery and Health Sciences, Urological Clinic, University of Trieste, Trieste, Italy.
¹⁶ Department of Surgery, S.H. Ho Urology Centre, The Chinese University of Hong Kong, Hong Kong, China.
¹⁷ Department of Urology, CHU-IUCT Toulouse, Toulouse, France.
¹⁸ Department of Urology, LMU Munich, Munich, Germany.
¹⁹ Urology Unit, Policlinico Tor Vergata Foundation, Rome, Italy.
²⁰ Division of Urology, Department of Surgical Sciences, Torino School of Medicine, AOU città della Salute e della Scienza di Torino, Torino, Italy.
²¹ GRC 5 Predictive Onco-Uro, AP-HP, Urology, Pitie-Salpetriere Hospital, Sorbonne University, Paris, France.
²² Urology Department, Claude Huriez Hospital, CHU Lille, Lille, France.
²³ CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, UMR9020-U1277 - CANTHER - Cancer Heterogeneity Plasticity and Resistance to Therapies, University Lille, Lille, France.
²⁴ Department of Urology, University Hospital Zürich, Zürich, Switzerland.
²⁵ Division of Urology, Department of Surgery, Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada.
²⁶ Department of Urology, Marienkrankenhaus Hamburg, Hamburg, Germany.
²⁷ Unit of Urology, Department of Medical and Surgical Specialities, Radiological Science and Public Health, ASST Spedali Civili di Brescia, University of Brescia, Brescia, Italy.
²⁸ Galdakao-Usansolo Hospital, Vizcaya, Spain.
²⁹ Department of Urology, Charité-Universitätsmedizin Berlin, Berlin, Germany.
³⁰ Unit of Urological Robotic Surgery and Renal Transplantation, Careggi Hospital, University of Florence, Florence, Italy.
³¹ Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy.
³² Department of Minimally Invasive and Robotic Urology, Wrocław Medical University, Wrocław, Poland.
³³ Department of Urology, Netherlands Cancer Institute, Amsterdam, Netherlands.
³⁴ Department of Urology, Faculty of Medicine, Istanbul Medeniyet University, Istanbul, Turkey.
³⁵ Division of Urology, Department of Surgery, University of Ottawa and Ottawa Hospital Research Institute, Ottawa, Canada.
³⁶ Department of Urology and Division of Experimental Oncology, Urological Research Institute, Vita-Salute San Raffaele, Milan, Italy.
³⁷ University of Zurich, Zurich, Switzerland.

PMID: 38961717
DOI: 10.1111/bju.16444

Abstract

Objectives: To assess the risk of venous thromboembolic events (VTEs) and bleeding with or without thromboprophylaxis during neoadjuvant chemotherapy in bladder cancer patients scheduled for radical cystectomy.

Materials and methods: We conducted a retrospective cohort study in 4886 patients with non-metastatic bladder cancer undergoing cystectomy across 28 centres in 13 countries between 1990 and 2021. Inverse probability weighting analyses were performed to estimate the effect of thromboprophylaxis on VTE and bleeding.

Results: In 147 patients (3%) VTEs were recorded within the first year. These occurred a median (interquartile range [IQR]) of 127 (82-198) days after bladder cancer diagnosis. Bleeding events occurred in 131 patients (3%) within the first year. These occurred a median (IQR) of 101 (83-171) days after cancer diagnosis. In inverse probability weighting analyses, compared to patients without thromboprophylaxis during chemotherapy, patients with thromboprophylaxis had not only a lower risk of VTE (hazard ratio [HR] 0.32, 95% confidence interval [CI] 0.12-0.81; P = 0.016) but also a lower bleeding risk (HR 0.03, 95% CI 0.09-0.12; P <0.0001). The retrospective nature of the study was its main limitation.

Conclusions: In this retrospective analysis, the benefit of thromboprophylaxis during neoadjuvant chemotherapy before cystectomy is in line with data from randomised trials in other malignancies. Our data suggest thromboprophylaxis is protective against VTEs and should be the standard of care during neoadjuvant chemotherapy.

Keywords: bladder cancer; bleeding; neoadjuvant chemotherapy; radical cystectomy; venous thromboembolic events.

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References

1. Bagrodia A, Sukhu R, Winer AG et al. Incidence and effect of thromboembolic events in radical cystectomy patients undergoing preoperative chemotherapy for muscle‐invasive bladder cancer. Clin Genitourin Cancer 2017; 16: e113–e120
1. Duivenvoorden WC, Daneshmand S, Canter D et al. Incidence, characteristics and implications of thromboembolic events in patients with muscle invasive urothelial carcinoma of the bladder undergoing neoadjuvant chemotherapy. J Urol 2016; 196: 1627–1633
1. Khorana AA, Soff GA, Kakkar AK et al. Rivaroxaban for thromboprophylaxis in high‐risk ambulatory patients with cancer. N Engl J Med 2019; 380: 720–728
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1. Agnelli G, George DJ, Kakkar AK et al. Semuloparin for thromboprophylaxis in patients receiving chemotherapy for cancer. N Engl J Med 2012; 366: 601–609

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Thromboprophylaxis during neoadjuvant chemotherapy for bladder cancer reduces thromboembolism and bleeding

Affiliations

Thromboprophylaxis during neoadjuvant chemotherapy for bladder cancer reduces thromboembolism and bleeding

Authors

Affiliations

Abstract

References

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LinkOut - more resources

Full Text Sources

Medical