The Effects of Statins on Prostate Cancer Patients Receiving Androgen Deprivation Therapy or Definitive Therapy: A Systematic Review and Meta-Analysis

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.

Association between Statin Use and Clinical Outcomes in Patients with De Novo Metastatic Prostate Cancer: A Propensity Score-weighted Analysis

“…In patients with prostate cancer who receive ADT as their primary treatment, the use of statins in conjunction with ADT has been shown to significantly reduce both all-cause mortality and cancer-specific mortality [ 27 ]. Prolonged use of ADT can lead to metabolic changes that may increase the risk of cardiovascular events [ 5 ].…”

Statin use and outcomes of oncological treatment for castration-resistant prostate cancer

“…Three recent meta-analyses have shown statins to be associated with improved overall survival in prostate cancer patients treated with ADT 13 , 21 , 27 . Two of those studies also found statins to be linked with better prostate cancer-specific survival 13 , 21 .…”

“…Three recent meta-analyses have shown statins to be associated with improved overall survival in prostate cancer patients treated with ADT 13 , 21 , 27 . Two of those studies also found statins to be linked with better prostate cancer-specific survival 13 , 21 . Especially, the statin use after initiation of ADT has provided most consistent results showing statins to improve prognosis in patients with advanced PCa.…”

“…those receiving specific cancer treatment 7 – 9 . Especially, prostate cancer patients on androgen deprivation therapy have been consistently reported to benefit from concurrent statin use 10 – 13 .…”

Prostate Cancer and the Mevalonate Pathway

“…Similarly, the combination of statins and radical prostatectomy improved cancer-specific mortality. However, the authors admitted that differences in the time, dose, and duration of statin treatment caused heterogeneity, and the most effective type of statin was not established [183].…”