Hanan Goldberg1, Faizan K Mohsin2, Refik Saskin3, Girish S Kulkarni4, Alejandro Berlin5, Miran Kenk6, Christopher J D Wallis7, Zachary Klaassen8, Thenappan Chandrasekar9, Ardalan E Ahmad10, Rashid K Sayyid11, Olli Saarela2, Linda Penn12, Shabbir M H Alibhai13, Neil Fleshner10. 1. Division of Urology, Department of Surgical Oncology, Princess Margaret Cancer Centre, University Health Network and the University of Toronto, Toronto, ON, Canada; Institute of Medical Science, University of Toronto, Toronto, ON, Canada; Department of Urology, SUNY Upstate Medical University, Syracuse, NY, USA; Institute for Clinical Evaluative Sciences, Toronto, ON, Canada. Electronic address: gohanan@gmail.com. 2. Dalla Lana School of Public Health, University of Toronto, Toronto, ON, Canada. 3. Institute for Clinical Evaluative Sciences, Toronto, ON, Canada. 4. Division of Urology, Department of Surgical Oncology, Princess Margaret Cancer Centre, University Health Network and the University of Toronto, Toronto, ON, Canada; Institute for Clinical Evaluative Sciences, Toronto, ON, Canada. 5. Radiation Medicine Program, Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada; Department of Radiation Oncology, University of Toronto, Toronto, ON, Canada; Techna Institute, University Health Network, Toronto, ON, Canada. 6. Division of Urology, Department of Surgical Oncology, Princess Margaret Cancer Centre, University Health Network and the University of Toronto, Toronto, ON, Canada. 7. Division of Urology, Department of Surgical Oncology, Princess Margaret Cancer Centre, University Health Network and the University of Toronto, Toronto, ON, Canada; Department of Urology, Vanderbilt University Medical Center, Nashville, TN, USA. 8. Division of Urology, Department of Surgery, Medical College of Georgia, Augusta University, Augusta, GA, USA; Georgia Cancer Center, Augusta, GA, USA. 9. Department of Urology, Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia PA, USA. 10. Division of Urology, Department of Surgical Oncology, Princess Margaret Cancer Centre, University Health Network and the University of Toronto, Toronto, ON, Canada; Institute of Medical Science, University of Toronto, Toronto, ON, Canada. 11. Division of Urology, Department of Surgery, Medical College of Georgia, Augusta University, Augusta, GA, USA. 12. Department of Medical Biophysics, University of Toronto, Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada. 13. Institute of Medical Science, University of Toronto, Toronto, ON, Canada; Department of Medicine, University Health Network and University of Toronto, Toronto, ON, Canada.
Abstract
BACKGROUND: The chemopreventive effect of various medications in prostate cancer (PCa) has gained interest. Specifically, the potential impact of statins on PCa incidence has been studied, but solely as a "drug family" overlooking the distinctive pharmacological properties of its two main subgroups: hydrophilic and hydrophobic statins. OBJECTIVE: To assess the impact of statin subgroups on PCa-specific mortality (PCSM), PCa diagnosis, and undergoing another prostate biopsy. DESIGN, SETTING, AND PARTICIPANTS: This is a population-based cohort study in Ontario identifying all men aged ≥66 yr with a history of a single negative prostate biopsy (representing healthy men at risk for PCa) between 1994 and 2016, who were not on any of the analyzed medications prior to the study, with a median follow-up of 9.42 yr (interquartile range 8.03 yr). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Using multivariable cause-specific hazard models with time-dependent covariates, the association of hydrophobic and hydrophilic statins with all study outcomes was analyzed. Other putative chemopreventive medications (including alpha-blockers, 5-alpha-reductase inhibitors, and proton-pump inhibitors), age, rurality, comorbidities, and study inclusion year were included in the models. RESULTS AND LIMITATIONS: Overall, 21 512 men were identified. Statins were taken by 11 401 patients (50.3%), 5184 men (24.1%) were diagnosed with PCa, and 805 (3.7%) died from it. Overall, 7556 patients (35.1%) underwent another biopsy. Any use of hydrophilic statins was associated with a 32.4% (95% confidence interval [CI] 12.9-47.5%), a 20% (95% CI 10-28%), and an 18% (95% CI 6.1-27.3%) decreased risk of PCSM, undergoing another prostate biopsy, and being diagnosed with PCa, respectively. Hydrophobic statins were associated with 17% (95% CI 2-31%) decreased PCSM. The study is limited by its retrospective nature, selection bias, and accompanying health-administrative database inaccuracies. CONCLUSIONS: Use of any statin may be associated with a lower hazard of PCSM, with hydrophilic statins showing a greater association with decreased PCa diagnosis rates. Preferentially prescribing one statin subgroup over another in men needs further exploration. PATIENT SUMMARY: Use of any statin may be associated with a lower probability of dying from prostate cancer. Hydrophilic statins (rosuvastatin and pravastatin) may also be more positively associated with a lower risk of undergoing an additional prostate biopsy and being diagnosed with prostate cancer in men aged ≥66 yr.
BACKGROUND: The chemopreventive effect of various medications in prostate cancer (PCa) has gained interest. Specifically, the potential impact of statins on PCa incidence has been studied, but solely as a "drug family" overlooking the distinctive pharmacological properties of its two main subgroups: hydrophilic and hydrophobic statins. OBJECTIVE: To assess the impact of statin subgroups on PCa-specific mortality (PCSM), PCa diagnosis, and undergoing another prostate biopsy. DESIGN, SETTING, AND PARTICIPANTS: This is a population-based cohort study in Ontario identifying all men aged ≥66 yr with a history of a single negative prostate biopsy (representing healthy men at risk for PCa) between 1994 and 2016, who were not on any of the analyzed medications prior to the study, with a median follow-up of 9.42 yr (interquartile range 8.03 yr). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Using multivariable cause-specific hazard models with time-dependent covariates, the association of hydrophobic and hydrophilic statins with all study outcomes was analyzed. Other putative chemopreventive medications (including alpha-blockers, 5-alpha-reductase inhibitors, and proton-pump inhibitors), age, rurality, comorbidities, and study inclusion year were included in the models. RESULTS AND LIMITATIONS: Overall, 21 512 men were identified. Statins were taken by 11 401 patients (50.3%), 5184 men (24.1%) were diagnosed with PCa, and 805 (3.7%) died from it. Overall, 7556 patients (35.1%) underwent another biopsy. Any use of hydrophilic statins was associated with a 32.4% (95% confidence interval [CI] 12.9-47.5%), a 20% (95% CI 10-28%), and an 18% (95% CI 6.1-27.3%) decreased risk of PCSM, undergoing another prostate biopsy, and being diagnosed with PCa, respectively. Hydrophobic statins were associated with 17% (95% CI 2-31%) decreased PCSM. The study is limited by its retrospective nature, selection bias, and accompanying health-administrative database inaccuracies. CONCLUSIONS: Use of any statin may be associated with a lower hazard of PCSM, with hydrophilic statins showing a greater association with decreased PCa diagnosis rates. Preferentially prescribing one statin subgroup over another in men needs further exploration. PATIENT SUMMARY: Use of any statin may be associated with a lower probability of dying from prostate cancer. Hydrophilic statins (rosuvastatin and pravastatin) may also be more positively associated with a lower risk of undergoing an additional prostate biopsy and being diagnosed with prostate cancer in men aged ≥66 yr.
Authors: Hanan Goldberg; Faizan K Mohsin; Thenappan Chandrasekar; Christopher J D Wallis; Zachary Klaassen; Ardalan E Ahmad; Refik Saskin; Miran Kenk; Olli Saarela; Girish S Kulkarni; Shabbir M H Alibhai; Neil Fleshner Journal: Can Urol Assoc J Date: 2022-05 Impact factor: 2.052
Authors: Abdulmajeed Aydh; Reza Sari Motlagh; Mishari Alshyarba; Keiichiro Mori; Satoshi Katayama; Nico Grossmann; Pawel Rajwa; Hadi Mostafai; Ekaterina Laukhtina; Benjamin Pradere; Fahad Quhal; Frederik König; Peter Nyirady; Pierre I Karakiewicz; Martin Haydter; Shahrokh F Shariat Journal: Cent European J Urol Date: 2021-12-06