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      The Prognostic Effect of Statin Use on Urologic Cancers : An Updated Meta-Analysis of 35 Observational Studies

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      , MD, , MD, , MD, , BS, , MD, PhD

      Medicine

      Wolters Kluwer Health

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          Abstract

          Recent studies suggest that statin may benefit cancer prognosis, especially through its radiosensitization effect. But controversy exists in other studies. Hence, we performed a meta-analysis of results from 35 studies to evaluate the effect of statin use on urologic cancers.

          We conducted computerized search from PubMed, Embase, and ISI Web of Knowledge through May 2015, screened the retrieved references, and collected and evaluated relevant information. We extracted and synthesized corresponding hazard ratios (HR) and confidence interval (CI) by using Review Manager 5.3 and STATA 13. This review was registered at PROSPERO with registration No. CRD42015020171.

          We selected total 35 retrospective studies and conducted a meta-analysis of results from these studies. The pooled results suggested no benefit of statin use to bladder cancer and renal cell carcinoma, except overall survival [HR = 0.81, 95% CI: 0.69–0.96]. However, significant improvement of prostate cancer prognosis including overall survival [HR = 0.82, 95% CI: 0.70–0.97] and cancer-specific survival [HR = 0.70, 95% CI: 0.59–0.83] was indicated, but not including tumor progression [HR = 0.84, 95% CI: 0.62–1.14]. Statin use improved biochemical recurrence of prostate cancer in radiotherapy patients [HR = 0.68, 95% CI: 0.54–0.85] but not in radical prostatectomy patients [HR = 0.97, 95% CI: 0.82–1.15].

          Current evidence suggests no benefit of statin use to bladder cancer and renal cell carcinoma, except in overall survival. While statin use benefited prostate cancer patients in overall survival, cancer-specific survival but not in tumor progression; it also improved biochemical recurrence in radiotherapy patients but not in radical patients. To verify these results, randomized controlled trials are necessary.

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          Most cited references 33

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          Use of statins and the risk of death in patients with prostate cancer.

          To determine whether the use of statins after prostate cancer diagnosis is associated with a decreased risk of cancer-related mortality and all-cause mortality and to assess whether this association is modified by prediagnostic use of statins. A cohort of 11,772 men newly diagnosed with nonmetastatic prostate cancer between April 1, 1998, and December 31, 2009, followed until October 1, 2012, was identified using a large population-based electronic database from the United Kingdom. Time-dependent Cox proportional hazards models were used to estimate adjusted hazard ratios (HRs) with 95% CIs of mortality outcomes associated with postdiagnostic use of statins, lagged by 1 year to account for latency considerations and to minimize reverse causality, and considering effect modification by prediagnostic use of statins. During a mean follow-up time of 4.4 years (standard deviation, 2.9 years), 3,499 deaths occurred, including 1,791 from prostate cancer. Postdiagnostic use of statins was associated with a decreased risk of prostate cancer mortality (HR, 0.76; 95% CI, 0.66 to 0.88) and all-cause mortality (HR, 0.86; 95% CI, 0.78 to 0.95). These decreased risks of prostate cancer mortality and all-cause mortality were more pronounced in patients who also used statins before diagnosis (HR, 0.55; 95% CI, 0.41 to 0.74; and HR, 0.66; 95% CI, 0.53 to 0.81, respectively), with weaker effects in patients who initiated the treatment only after diagnosis (HR, 0.82; 95% CI, 0.71 to 0.96; and HR, 0.91; 95% CI, 0.82 to 1.01, respectively). Overall, the use of statins after diagnosis was associated with a decreased risk in prostate cancer mortality. However, this effect was stronger in patients who also used statins before diagnosis.
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            The role of statins in cancer therapy.

            Administration of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, or statins, to ambulatory patients is associated with a lower incidence of long-term adverse cardiovascular events, including death, myocardial infarction, stroke, atrial fibrillation, and renal dysfunction. However, increasing clinical evidence suggests that statins, independent of their effects on serum cholesterol levels, may also play a potential role in the prevention and treatment of cancer. Specifically, statins have been shown to exert several beneficial antineoplastic properties, including decreased tumor growth, angiogenesis, and metastasis. The feasibility and efficacy of statins for the prevention and treatment of cancer is reviewed.
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              Association between use of β-blockers and prostate cancer-specific survival: a cohort study of 3561 prostate cancer patients with high-risk or metastatic disease.

              We recently reported reduced prostate cancer (PCa)-specific mortality for β-blocker users among patients receiving androgen-deprivation therapy in a health survey cohort including 655 PCa patients. Information on clinical characteristics was limited. To assess the association between β-blockers and PCa-specific mortality in a cohort of 3561 prostate cancer patients with high-risk or metastatic disease, and to address potential confounding from the use of statins or acetylsalicylic acid (ASA). Clinical information from all men reported to the Cancer Registry of Norway with a PCa diagnosis between 2004 and 2009 (n=24 571) was coupled with information on filled prescriptions between 2004 and 2011 from the Norwegian Prescription Database. Exclusion criteria were low- or intermediate-risk disease; planned radiotherapy or radical prostatectomy; initiation of β-blocker, ASA, or statin use after diagnosis where applicable; missing information on baseline Gleason score, prostate-specific antigen level, T stage or performance status; and missing follow-up. Cox proportional hazards modelling and competing risk regression modelling were used to analyse the effects of β-blocker use on all-cause and PCa-specific mortality, respectively. Differences between β-blocker users and nonusers regarding baseline clinical characteristics were assessed by the Wilcoxon-Mann-Whitney U test, Pearson chi-square test, and Student t test. Median follow-up was 39 mo. β-Blocker use was associated with reduced PCa mortality (adjusted subhazard ratio: 0.79; 95% confidence interval [CI], 0.68-0.91; p value: 0.001). The observed reduction in PCa mortality was independent of the use of statins or ASA. We observed no association with all-cause mortality (adjusted hazard ratio: 0.92; 95% CI, 0.83-1.02). The main limitations of the study were the observational study design and short follow-up. β-Blocker use was associated with reduced PCa-specific mortality in patients with high-risk or metastatic disease at the time of diagnosis. Our findings need validation from further observational studies. Copyright © 2013 European Association of Urology. Published by Elsevier B.V. All rights reserved.
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                Author and article information

                Journal
                Medicine (Baltimore)
                Medicine (Baltimore)
                MEDI
                Medicine
                Wolters Kluwer Health
                0025-7974
                1536-5964
                September 2015
                11 September 2015
                : 94
                : 36
                Affiliations
                From the Institute of Gansu Nephro-Urological Clinical Center, Institute of Urology, Department of Urology, Key Laboratory of Urological Disease of Gansu Province, Lanzhou University Second Hospital, Lanzhou, P.R. China (YL, D-LS, HX, S-JF, LY).
                Author notes
                Correspondence: Li Yang, Department of Urology, Lanzhou University Second Hospital, Chengguan District, Lanzhou 730000, P.R. China (e-mail: yuze250@ 123456163.com ).
                Article
                01523
                10.1097/MD.0000000000001523
                4616645
                26356727
                b58a0ea1-9b60-4fd3-82da-783e2df5e79c
                Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.

                This is an open access article distributed under the Creative Commons Attribution-NonCommercial License, where it is permissible to download, share and reproduce the work in any medium, provided it is properly cited. The work cannot be used commercially. http://creativecommons.org/licenses/by-nc/4.0

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