Konrad H Stopsack1, Alexandra J Greenberg2, Lorelei A Mucci3,4. 1. Department of Internal Medicine, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA. stopsack@post.harvard.edu. 2. Department of Neurology, Mayo Clinic, Rochester, MN, USA. 3. Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA. 4. Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
Abstract
PURPOSE: Most prostate cancer patients also have comorbidities that are treated with both prescription and nonprescription medications; furthermore, many use dietary supplements. We assess their association with prognosis after prostate cancer diagnosis, and we discuss methodological challenges and clinical implications. METHODS: We reviewed high-quality observational studies investigating the association of commonly used medications and supplements with prostate cancer-specific mortality. RESULTS: There is preliminary evidence that statins and metformin use may be associated with lower risk of cancer-specific mortality after prostate cancer diagnosis; conversely, high calcium and multivitamin supplementation may be associated with increased risk. Evidence is inconclusive for nonsteroidal anti-inflammatory drugs, acetylsalicylic acid (aspirin), insulin, antihypertensives such as angiotensin-converting enzyme inhibitors and beta-blockers, digoxin, and warfarin. Common limitations of the internal validity of studies examined include unmeasured confounding and confounding by indication, competing risks, and time-related biases such as immortal time bias. The majority of studies focused on Caucasian men with specific comorbidities, while heterogeneity among patients and tumors was mostly not assessed. CONCLUSIONS: Commonly prescribed medications and over-the-counter supplements may influence prognosis among prostate cancer patients. Further well-designed pharmacoepidemiologic studies and randomized controlled trials of selected medications in appropriate patient groups are necessary before these drugs can bear new indications for prostate cancer treatment. We discuss considerations when deciding about use of these drugs in clinical practice at the present time.
PURPOSE: Most prostate cancerpatients also have comorbidities that are treated with both prescription and nonprescription medications; furthermore, many use dietary supplements. We assess their association with prognosis after prostate cancer diagnosis, and we discuss methodological challenges and clinical implications. METHODS: We reviewed high-quality observational studies investigating the association of commonly used medications and supplements with prostate cancer-specific mortality. RESULTS: There is preliminary evidence that statins and metformin use may be associated with lower risk of cancer-specific mortality after prostate cancer diagnosis; conversely, high calcium and multivitamin supplementation may be associated with increased risk. Evidence is inconclusive for nonsteroidal anti-inflammatory drugs, acetylsalicylic acid (aspirin), insulin, antihypertensives such as angiotensin-converting enzyme inhibitors and beta-blockers, digoxin, and warfarin. Common limitations of the internal validity of studies examined include unmeasured confounding and confounding by indication, competing risks, and time-related biases such as immortal time bias. The majority of studies focused on Caucasian men with specific comorbidities, while heterogeneity among patients and tumors was mostly not assessed. CONCLUSIONS: Commonly prescribed medications and over-the-counter supplements may influence prognosis among prostate cancerpatients. Further well-designed pharmacoepidemiologic studies and randomized controlled trials of selected medications in appropriate patient groups are necessary before these drugs can bear new indications for prostate cancer treatment. We discuss considerations when deciding about use of these drugs in clinical practice at the present time.
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