Sean O'Farrell1,2, Karin Sandström1, Hans Garmo1,3, Pär Stattin4, Lars Holmberg1,2,3,5, Jan Adolfsson6,7, Mieke Van Hemelrijck1,2,8. 1. Division of Cancer Studies, Cancer Epidemiology Group, King's College London, London, UK. 2. NIHR Guy's and St Thomas' NHS Foundation Trust, King's College London's Comprehensive Biomedical Research Centre, London, UK. 3. Regional Cancer Centre, Uppsala Örebro, Uppsala, Sweden. 4. Department of Surgical and Perioperative Sciences, Urology and Andrology, Umeå University, Umeå, Sweden. 5. Department of Surgical Sciences, Uppsala University, Uppsala, Sweden. 6. Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden. 7. Swedish Council for Health Technology Assessment, Stockholm, Sweden. 8. Institute of Environmental Medicine, Karolinska Institute, Stockholm, Sweden.
Abstract
OBJECTIVES: To investigate the risk of thromboembolic disease (TED) in men with prostate cancer (PCa) on androgen deprivation therapy (ADT), while accounting for known TED risk factors. MATERIALS AND METHODS: We assessed TED risk for 42 263 men with PCa who were receiving ADT compared with a matched cohort of 190 930 without PCa. The associations between ADT and deep vein thrombosis (DVT) or pulmonary embolism (PE) were analysed using multivariate Cox proportional hazard regression models, while accounting for previous PCa-related surgeries and the following proxies for disease progression: transurethral resection of the prostate, palliative radiotherapy and nephrostomy. RESULTS: Between 1997 and 2013, 11 242 men with PCa received anti-androgen monotherapy, 26 959 men received gonadotropin-releasing hormone (GnRH) agonists, 1 091 men received combined androgen blockade and 3 789 men underwent orchiectomy. When accounting for previous surgeries and proxies of disease progression, GnRH agonist users and surgically castrated men had a higher risk of TED than the comparison cohort: hazard ratios (HRs) 1.67 (95% confidence interval [CI] 1.40-1.98) and 1.61 (95% CI 1.15-2.28), respectively. Men on anti-androgen monotherapy had a lower risk: HR for DVT 0.49 (95% CI 0.33-0.74). TED risk was highest among those who switched from anti-androgen to GnRH agonists: HR for PE 2.55 (95% CI 1.76-3.70). This increased from 2.52 (95% CI 1.54-4.12) in year 1, to 4.05 (95% CI 2.51-6.55) in year 2. CONCLUSION: The incidence of TED among men on ADT increased with the duration of therapy and the risk was highest for those who switched regimen, suggesting that disease progression as well as ADT contribute to the propagation of TED risk. Nonetheless, these findings support the hypothesis that only men with a relevant indication should receive systemic ADT.
OBJECTIVES: To investigate the risk of thromboembolic disease (TED) in men with prostate cancer (PCa) on androgen deprivation therapy (ADT), while accounting for known TED risk factors. MATERIALS AND METHODS: We assessed TED risk for 42 263 men with PCa who were receiving ADT compared with a matched cohort of 190 930 without PCa. The associations between ADT and deep vein thrombosis (DVT) or pulmonary embolism (PE) were analysed using multivariate Cox proportional hazard regression models, while accounting for previous PCa-related surgeries and the following proxies for disease progression: transurethral resection of the prostate, palliative radiotherapy and nephrostomy. RESULTS: Between 1997 and 2013, 11 242 men with PCa received anti-androgen monotherapy, 26 959 men received gonadotropin-releasing hormone (GnRH) agonists, 1 091 men received combined androgen blockade and 3 789 men underwent orchiectomy. When accounting for previous surgeries and proxies of disease progression, GnRH agonist users and surgically castrated men had a higher risk of TED than the comparison cohort: hazard ratios (HRs) 1.67 (95% confidence interval [CI] 1.40-1.98) and 1.61 (95% CI 1.15-2.28), respectively. Men on anti-androgen monotherapy had a lower risk: HR for DVT 0.49 (95% CI 0.33-0.74). TED risk was highest among those who switched from anti-androgen to GnRH agonists: HR for PE 2.55 (95% CI 1.76-3.70). This increased from 2.52 (95% CI 1.54-4.12) in year 1, to 4.05 (95% CI 2.51-6.55) in year 2. CONCLUSION: The incidence of TED among men on ADT increased with the duration of therapy and the risk was highest for those who switched regimen, suggesting that disease progression as well as ADT contribute to the propagation of TED risk. Nonetheless, these findings support the hypothesis that only men with a relevant indication should receive systemic ADT.
Authors: Sakthivel Muniyan; Lei Xi; Kaustubh Datta; Anindita Das; Benjamin A Teply; Surinder K Batra; Rakesh C Kukreja Journal: Biochim Biophys Acta Rev Cancer Date: 2020-06-11 Impact factor: 10.680