The effect of statins on advanced prostate cancer patients with androgen deprivation therapy or abiraterone/enzalutamide: A systematic review and meta‐analysis

Yang, Hui; Pang, Lizhen; Hu, Xiaopeng; Wang, Wei; Xu, Bifang; Zhang, Xiaodong

doi:10.1111/jcpt.13092

Cited by 17 publications

(21 citation statements)

References 29 publications

(47 reference statements)

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“…In an anecdotal case, a patient with bone metastatic CRPC who started on abiraterone and prednisolone, and soon after on atorvastatin, achieved a complete PSA response with no evidence of bone metastasis in six months [ 169 ]. Reports indicating that statins improve PSA decline and overall survival of abiraterone-treated patients [ 170 , 171 ] corroborate observations that statin use significantly increases progression-free, and overall, survival of abiraterone-treated CPRC patients [ 172 ]. These clinical results support previous conclusions that this is, in part, due to a decrease in de novo cholesterol and androgen synthesis [ 126 , 173 , 174 , 175 ].…”

Section: Effect Of a Class Of Drugs That Inhibit Cholesterol Synthesis On Prostate Cancer (Pca)supporting

confidence: 56%

Inhibition of Scavenger Receptor Class B Type 1 (SR-B1) Expression and Activity as a Potential Novel Target to Disrupt Cholesterol Availability in Castration-Resistant Prostate Cancer

et al. 2021

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There have been several studies that have linked elevated scavenger receptor class b type 1 (SR-B1) expression and activity to the development and progression of castration-resistant prostate cancer (CRPC). SR-B1 facilitates the influx of cholesterol to the cell from lipoproteins in systemic circulation. This influx of cholesterol may be important for many cellular functions, including the synthesis of androgens. Castration-resistant prostate cancer tumors can synthesize androgens de novo to supplement the loss of exogenous sources often induced by androgen deprivation therapy. Silencing of SR-B1 may impact the ability of prostate cancer cells, particularly those of the castration-resistant state, to maintain the intracellular supply of androgens by removing a supply of cholesterol. SR-B1 expression is elevated in CRPC models and has been linked to poor survival of patients. The overarching belief has been that cholesterol modulation, through either synthesis or uptake inhibition, will impact essential signaling processes, impeding the proliferation of prostate cancer. The reduction in cellular cholesterol availability can impede prostate cancer proliferation through both decreased steroid synthesis and steroid-independent mechanisms, providing a potential therapeutic target for the treatment of prostate cancer. In this article, we discuss and highlight the work on SR-B1 as a potential novel drug target for CRPC management.

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Section: Effect Of a Class Of Drugs That Inhibit Cholesterol Synthesis On Prostate Cancer (Pca)supporting

confidence: 56%

Inhibition of Scavenger Receptor Class B Type 1 (SR-B1) Expression and Activity as a Potential Novel Target to Disrupt Cholesterol Availability in Castration-Resistant Prostate Cancer

et al. 2021

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“…ARSi drives changes in metabolic profiles and body composition. Previous studies demonstrate relationships between ARSi therapy and lipid metabolism and statin use (23)(24)(25). Both abiraterone and enzalutamide can induce increases in body fat mass and decreases in lean body mass (26,27).…”

Section: Discussionmentioning

confidence: 96%

Association of Body Composition With Survival and Treatment Efficacy in Castration-Resistant Prostate Cancer

et al. 2020

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Objectives: The association of body composition with survival and the efficacy of first-line treatment was investigated in patients with castration-resistant prostate cancer (CRPC). Methods: The records of CRPC patients treated with docetaxel or androgen receptor signaling inhibitors (ARSi) between 2005 and 2018 were reviewed. Skeletal muscle index (SMI), visceral fat index, and subcutaneous fat index were evaluated using pretreatment computed tomography images. Results: Of 230 eligible patients, 144 received docetaxel, and 86 received ARSi as the first-line treatment for CRPC. The SMI hi (based on median values) group had higher prostate-specific antigen (PSA) progression-free survival (median 13.5 vs. 8.3 months, p = 0.030), radiologic progression-free survival (14.9 vs. 9.1 months, p < 0.001), and overall survival (24.1 vs. 16.9 months, p = 0.015) than the SMI lo group. In docetaxel-treated patients, the SMI hi group had higher PSA progression-free survival (13.5 vs. 5.9 months, p = 0.016) and radiologic progression-free survival (14.6 vs. 6.7 months, p < 0.001) than the SMI lo group. However, PSA progression-free survival and radiologic progression-free survival were comparable between the two groups in ARSi-treated patients. SMI was independently associated with the risk of radiologic progression in patients treated with docetaxel but not in those treated with ARSi. Conclusions: High skeletal muscle mass may be associated with reduced risk of disease progression and mortality in patients with CRPC. However, the significance of these relationships is limited in patients treated with docetaxel. These results suggest that assessing skeletal muscle mass may be worthwhile when selecting treatments for CRPC; however, further prospective validation and large-scale studies are needed.

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“…Considering the previous studies, we hypothesized that the beneficial effects of statins relate to cancer progression, which would explain the difference in survival. In three previous studies, statin use has been linked to better survival among ADT-treated patients [ 10 , 18 , 19 ]. These studies suggest that statins may enhance the therapeutic effect of ADT.…”

Section: Discussionmentioning

confidence: 99%

Prostate cancer prognosis after initiation of androgen deprivation therapy among statin users. A population-based cohort study

Peltomaa

Raittinen

Talala

et al. 2021

Prostate Cancer Prostatic Dis

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Purpose Statins’ cholesterol-lowering efficacy is well-known. Recent epidemiological studies have found that inhibition of cholesterol synthesis may have beneficial effects on prostate cancer (PCa) patients, especially patients treated with androgen deprivation therapy (ADT). We evaluated statins’ effect on prostate cancer prognosis among patients treated with ADT. Materials and methods Our study population consisted of 8253 PCa patients detected among the study population of the Finnish randomized study of screening for prostate cancer. These were limited to 4428 men who initiated ADT during the follow-up. Cox proportional regression model adjusted for tumor clinical characteristics and comorbidities was used to estimate hazard ratios for risk of PSA relapse after ADT initiation and prostate cancer death. Results During the median follow-up of 6.3 years after the ADT initiation, there were 834 PCa deaths and 1565 PSA relapses in a study cohort. Statin use after ADT was associated with a decreased risk of PSA relapse (HR 0.73, 95% CI 0.65–0.82) and prostate cancer death (HR 0.82; 95% CI 0.69–0.96). In contrast, statin use defined with a one-year lag (HR 0.89, 95% CI 0.76–1.04), statin use before ADT initiation (HR 1.12, 95% CI 0.96–1.31), and use in the first year on ADT (HR 1.02, 95% CI 0.85–1.24) were not associated with prostate cancer death, without dose dependency. Conclusion Statin use after initiation of ADT, but not before, was associated with improved prostate cancer prognosis.

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The effect of statins on advanced prostate cancer patients with androgen deprivation therapy or abiraterone/enzalutamide: A systematic review and meta‐analysis

Cited by 17 publications

References 29 publications

Inhibition of Scavenger Receptor Class B Type 1 (SR-B1) Expression and Activity as a Potential Novel Target to Disrupt Cholesterol Availability in Castration-Resistant Prostate Cancer

Inhibition of Scavenger Receptor Class B Type 1 (SR-B1) Expression and Activity as a Potential Novel Target to Disrupt Cholesterol Availability in Castration-Resistant Prostate Cancer

Association of Body Composition With Survival and Treatment Efficacy in Castration-Resistant Prostate Cancer

Prostate cancer prognosis after initiation of androgen deprivation therapy among statin users. A population-based cohort study

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