Raj Tiwari1, Neil Fleshner2. 1. Division of Urology, University Health Network, University of Toronto, 700 University Ave, Toronto, ON, M5G 1X6, Canada. raj.tiwari@uhn.ca. 2. Division of Urology, University Health Network, University of Toronto, 700 University Ave, Toronto, ON, M5G 1X6, Canada.
Abstract
PURPOSE OF REVIEW: A sound scientific basis has been emerging on the anti-neoplastic role of metformin, statins and dietary interventions. However, evidence in prostate cancer patients remains mixed owing to an absence of completed randomized trials. This overview examines the rationale for metformin, statins and dietary intervention for secondary prevention in men on active surveillance by summarizing current evidence base and biological mechanisms in influencing cancer progression and mortality. METHODS: A comprehensive literature search was performed to identify studies that evaluated the role of metformin, statins and diet in the secondary prevention of prostate cancer as well as those that described the anti-cancer mechanisms of these agents. The search included Pubmed, MEDLINE, EMBASE and Cochrane library from inception till August 2021. RESULTS: A total of 14 trials on metformin, 21 trials on statins and 13 trials on dietary measures were evaluated. Majority were observational population-based cohort studies or meta-analysis of them. Three ongoing prospective randomized controlled trials were also reported. Overall, mixed results were obtained. CONCLUSIONS: The role of metformin and statins remains promising with several trials showing reduced rates of progression and cancer specific mortality. Combination therapy strategies have also been evaluated in more advanced patients showing synergism. Dietary interventions especially fruits, vegetables and fish intake has shown some benefit albeit with mixed results for others like legumes, red meat, coffee and multivitamins. Several ongoing randomized trials will provide stronger evidence in the future for secondary prevention.
PURPOSE OF REVIEW: A sound scientific basis has been emerging on the anti-neoplastic role of metformin, statins and dietary interventions. However, evidence in prostate cancer patients remains mixed owing to an absence of completed randomized trials. This overview examines the rationale for metformin, statins and dietary intervention for secondary prevention in men on active surveillance by summarizing current evidence base and biological mechanisms in influencing cancer progression and mortality. METHODS: A comprehensive literature search was performed to identify studies that evaluated the role of metformin, statins and diet in the secondary prevention of prostate cancer as well as those that described the anti-cancer mechanisms of these agents. The search included Pubmed, MEDLINE, EMBASE and Cochrane library from inception till August 2021. RESULTS: A total of 14 trials on metformin, 21 trials on statins and 13 trials on dietary measures were evaluated. Majority were observational population-based cohort studies or meta-analysis of them. Three ongoing prospective randomized controlled trials were also reported. Overall, mixed results were obtained. CONCLUSIONS: The role of metformin and statins remains promising with several trials showing reduced rates of progression and cancer specific mortality. Combination therapy strategies have also been evaluated in more advanced patients showing synergism. Dietary interventions especially fruits, vegetables and fish intake has shown some benefit albeit with mixed results for others like legumes, red meat, coffee and multivitamins. Several ongoing randomized trials will provide stronger evidence in the future for secondary prevention.
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