A D Raval1,2, D Thakker3, H Negi4, A Vyas5, H Kaur6, M W Salkini7. 1. Department of Pharmaceutical Systems and Policy, School of Pharmacy, West Virginia University, Morgantown, WV, USA. 2. Healthcore, Inc., Wilmington, DE, USA. 3. Health Outcomes Research, Capita India, Mumbai, India. 4. Department of Pharmacology, Post-Graduate Medical Education and Research Institute (PGIMER), Chandigarh, India. 5. Department of Epidemiology, School of Public Health, Rutgers, the State University of New Jersey, Piscataway, NJ, USA. 6. Department of Hospital Medicine, Cleveland Clinic, Cleveland, OH, USA. 7. Department of Urology, School of Medicine, West Virginia University, Morgantown, WV, USA.
Abstract
BACKGROUND: Mixed evidence exists regarding the effects of statins among men with prostate cancer. We aimed to determine the association between statin use and clinical outcomes in prostate cancer using systematic review and meta-analysis. METHODS: Original articles published until second week of August 2015 were searched in electronic databases (Medline-Ovid, Pubmed, Scopus, The Cochrane Library, Web of Science, ProQuest) for studies on statin use in prostate cancer. The main clinical outcomes for the review were: biochemical recurrence (BCR), metastases, and all-cause and prostate cancer-specific mortality. Meta-analysis was performed to calculate the pooled hazard ratio (pHR) and their 95% confidence interval (95% CI). Heterogeneity between the studies was examined using I(2) statistics. Meta-regression was performed, wherever significant heterogeneity was found in the meta-analyses, to find factors associated with poor outcomes, and sensitivity analyses were conducted to assess the robustness of findings. The analyses were conducted using RevMan v5.3, STATA v14, and R v3.1.1. RESULTS: Out of the 1002 retrieved citations, 34 observational cohort studies met the inclusion criteria. Statin use was associated with a 21% reduction in the risk of BCR among those treated with radiation therapy (pHR: 0.79, 95% CI: 0.65, 0.95, P-value=0.01, 10 studies, I(2)=54%), whereas it was not associated with the BCR among those treated with radical prostatectomy (pHR: 0.94, 95% CI: 0.81, 1.09, P-value=0.43, 15 studies, I(2)=65%). Statin use was associated with a 22% reduction in the risk of metastases (pHR: 0.78, 95% CI: 0.68, 0.87, P-value<0.001, 6 studies, I(2)=0%), and a 24% reduction in risk of both all-cause mortality (pHR: 0.76, 95% CI: 0.63, 0.91, P-value=0.004, 6 studies, I(2)=71%), and prostate cancer-specific mortality (pHR: 0.76, 95% CI: 0.64, 0.89, P-value=0.0007, 5 studies, I(2)=40%). CONCLUSIONS: Our systematic review found that statin significantly reduced the all-cause and prostate cancer-specific mortality and improved the BCR in certain subgroup of men with prostate cancer. In future, randomized controlled trials should be conducted to establish efficacy of statins among men with prostate cancer.
BACKGROUND: Mixed evidence exists regarding the effects of statins among men with prostate cancer. We aimed to determine the association between statin use and clinical outcomes in prostate cancer using systematic review and meta-analysis. METHODS: Original articles published until second week of August 2015 were searched in electronic databases (Medline-Ovid, Pubmed, Scopus, The Cochrane Library, Web of Science, ProQuest) for studies on statin use in prostate cancer. The main clinical outcomes for the review were: biochemical recurrence (BCR), metastases, and all-cause and prostate cancer-specific mortality. Meta-analysis was performed to calculate the pooled hazard ratio (pHR) and their 95% confidence interval (95% CI). Heterogeneity between the studies was examined using I(2) statistics. Meta-regression was performed, wherever significant heterogeneity was found in the meta-analyses, to find factors associated with poor outcomes, and sensitivity analyses were conducted to assess the robustness of findings. The analyses were conducted using RevMan v5.3, STATA v14, and R v3.1.1. RESULTS: Out of the 1002 retrieved citations, 34 observational cohort studies met the inclusion criteria. Statin use was associated with a 21% reduction in the risk of BCR among those treated with radiation therapy (pHR: 0.79, 95% CI: 0.65, 0.95, P-value=0.01, 10 studies, I(2)=54%), whereas it was not associated with the BCR among those treated with radical prostatectomy (pHR: 0.94, 95% CI: 0.81, 1.09, P-value=0.43, 15 studies, I(2)=65%). Statin use was associated with a 22% reduction in the risk of metastases (pHR: 0.78, 95% CI: 0.68, 0.87, P-value<0.001, 6 studies, I(2)=0%), and a 24% reduction in risk of both all-cause mortality (pHR: 0.76, 95% CI: 0.63, 0.91, P-value=0.004, 6 studies, I(2)=71%), and prostate cancer-specific mortality (pHR: 0.76, 95% CI: 0.64, 0.89, P-value=0.0007, 5 studies, I(2)=40%). CONCLUSIONS: Our systematic review found that statin significantly reduced the all-cause and prostate cancer-specific mortality and improved the BCR in certain subgroup of men with prostate cancer. In future, randomized controlled trials should be conducted to establish efficacy of statins among men with prostate cancer.
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