The effect of statins on prostate cancer recurrence and mortality after definitive therapy: a systematic review and meta-analysis

Abstract

In this work, we aim to further analyze the association of statins use with biochemical recurrence (BCR) of prostate cancer (PCa) and PCa-specific mortality after definitive therapy. A systematic literature search of PubMed, MEDLINE, and EMBASE through Jul 2015 was conducted. Pooled Hazard ratio (HR) estimates with corresponding 95% confidence intervals (CIs) were calculated using random-effects model. STATA version 10 (Stata corporation, college station, TX) was employed to conduct all statistical analyses. A total of 22 and 8 studies contributed to the biochemical recurrence analysis and PCa-specific mortality, respectively. 13 trials were included for BCR-free survival analysis. The combined result showed statins users had lowered 12% BCR risk of PCa compared with non-users (HR = 0.88, 95%CI: 0.765–0.998) (p < 0.05). The association was null among the men who underwent radical prostatectomy as primary therapy (HR = 0.96, 95%CI: 0.83–1.09), while the improved outcomes had be seen among patients who received radiation therapy (HR = 0.67, 95%CI: 0.48–0.86). After excluding the patients undergoing ADT, participants did not benefit from statins use (HR = 0.94, 95%CI: 0.77–1.11). Meanwhile, long-term statins using did not alter recurrence risk. A lower risk of prostate cancer-specific mortality was observed among statins users (HR = 0.68, 95%CI: 0.56–0.80). There was a plausible trend towards increasing the BCR-free survival rate among statins users.

Increased transcriptional and metabolic capacity for lipid metabolism in the peripheral zone of the prostate may underpin its increased susceptibility to cancer

“…These results are consistent with reports that pharmaceutical interventions, e.g. statins that target cholesterol metabolism, are associated with reduced prostate cancer recurrence [ 35 , 36 ].…”

High expression of SLCO2B1 is associated with prostate cancer recurrence after radical prostatectomy

“…Statins, a class of cholesterol-lowering medications that inhibit 3-hydroxy-3-methl-glutaryl-coenzyme A reductase, are also substrates of SLCO2B1 and have been shown to act as an anticancer drug in various types of cancers [ 35 ]. In PCa, clinical studies have shown the controversial results in statin treatment after RP [ 36 – 39 ]. It has been reported that DHEAS uptake is inhibited by statins in PCa cell lines [ 40 ], and statin treatment decreased castration resistant progression with lower intra-tumoral androgen levels in murine models [ 41 ].…”

Access and concentrations of atorvastatin in the prostate in men with prostate cancer

“…Compared to nonusers, statin use has been associated with reduced risk of advanced prostate cancer and enhanced biochemical relapse‐free survival after either radical prostatectomy or radiation therapy in several epidemiological studies . Statin users have also been reported to have improved prostate cancer‐specific survival compared to nonusers, especially in the context of androgen deprivation therapy . Improved progression‐free and disease‐specific survival among statin users have also been reported after radical prostatectomy, although not all studies agree .…”

“…7,8 Statin users have also been reported to have improved prostate cancer-specific survival compared to nonusers, especially in the context of androgen deprivation therapy. [9][10][11] Improved progression-free and disease-specific survival among statin users have also been reported after radical prostatectomy, 12 although not all studies agree. 13 Survival benefits are likely to depend on treatment compliance, as lowered risk of disease recurrence has been observed only in men whose serum cholesterol decreases after statin intervention.…”