Abstract

Mortality associated with statin use has been reported in prostate cancer (PCa) patients treated with androgen deprivation therapy (ADT) or definitive therapy in several observational studies, although the results have varied. This study aimed to analyze the association of statin use with all-cause mortality and cancer-specific mortality among PCa patients receiving ADT or definitive therapy as their primary treatment and to examine the effect of statin initiation (pre-ADT) timing on outcomes. A systematic literature search of PubMed, the Cochrane library, and Embase was conducted from database inception to 4 October 2021. In total, 12 eligible studies from 976 references were included in the final analysis. The results showed that statin use was associated with a significant reduction in the risks of all-cause mortality (hazard ratio (HR) = 0.73, 95% confidence interval (CI) = 0.64–0.84, p < 0.0001) and cancer-specific mortality (HR = 0.61, 95% CI = 0.49–0.77, p < 0.0001) in PCa patients receiving ADT. However, statin use before ADT initiation did not significantly lower the risk of all-cause mortality (HR = 0.87, 95% CI = 0.66–1.16, p = 0.35) or cancer-specific mortality (HR = 0.84, 95% CI = 0.62–1.13, p = 0.25) in advanced PCa patients receiving ADT. In contrast, statin use was not associated with a significantly reduced risk of all-cause mortality (HR = 0.69, 95% CI = 0.39–1.21, p = 0.20), but it was associated with a reduced risk of cancer-specific mortality (HR = 0.82, 95% CI = 0.68–0.98, p = 0.03) in PCa patients receiving definitive therapy. This review indicated that statin use in combination with ADT was correlated with better all-cause and cancer-specific mortality in PCa patients. However, the beneficial effect might not come from statin use before ADT initiation. In addition, statin use in combination with definitive therapy was correlated with a reduced risk of cancer-specific mortality in PCa patients. In the future, randomized controlled trials are needed to validate the efficacy of statin use in combination with primary treatment for PCa among PCa patients.

Highlights

  • Statins have been widely used for decades to decrease serum cholesterol levels and the risk of cardiovascular disease [1]

  • This review indicated that statin use in combination with androgen deprivation therapy (ADT) was correlated with better all-cause and cancer-specific mortality in prostate cancer (PCa) patients

  • The beneficial effect might not come from statin use before ADT initiation

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Summary

Introduction

Statins have been widely used for decades to decrease serum cholesterol levels and the risk of cardiovascular disease [1]. Statins have received considerable attention due to their potential anticancer properties [2]. Several in vitro studies showed that statins prevent the progression of prostate cancer (PCa) via cholesterol-dependent and cholesterol-independent mechanisms [3]. PCa patients are usually older, and a high proportion of patients coexist with hyperlipidemia treated with statins [4]. The anticancer effect of statins in these patients is of interest. Some patients are diagnosed as low risk with a favorable outcome, but others have a more aggressive form of cancer [5]. Many observational studies have investigated the effects of statins on several outcomes regarding cancer progression, the association between statin

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