Benefits of Statins + ADT in Advanced Prostate Cancer
abstract
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Access this abstract now Full Text Available for ClinicalKey SubscribersBACKGROUND
Statins are thought to possess antineoplastic properties related to their effect on cell proliferation and steroidogenesis. Progression to castrate resistant prostate cancer (CaP) includes de-regulation of androgen synthesis suggesting a role for statins in this setting. Our goal was to assess the role of statin use on oncologic outcomes in patients with advanced CaP being treated with androgen deprivation therapy (ADT).
METHODS
The national VA database was used to identify all men diagnosed with CaP who were treated with ADT for at least 6 months between 2000 and 2008 with follow-up through May 2016. Our cohort was stratified based on statin use of at least 6 months duration during the same time. Multivariable Cox proportional hazards analyses with inverse propensity score weighted (IPSW) adjustment were calculated to assess for primary outcomes of CaP-specific survival (CSS), overall survival (OS) and skeletal related events (SREs).
RESULTS
A total of 87,346 patients on ADT were included in the study cohort, 53,360 patients used statins and 33,986 did not. Statin users were younger in age (median 73 vs. 76, P < 0.001), more likely to have a higher Charlson comorbidity index (CCI) >3 (3.1% vs. 2.5%, P < 0.001) and more likely to have a high grade (Gleason score 8-10) cancer (12.3% vs. 10.9%, P < 0.001). Statin users had longer OS (median 6.5 vs. 4.0 years P < 0.001) and decreased death from CaP (5-year CSS 94.0% vs. 87.3%, P < 0.001). Statin use was also associated with longer time to a SRE (median 5.9 vs. 3.7 years, P < 0.001). On multivariable Cox proportional hazards analysis with inverse propensity score weighted, statin use was an independent predictor of improved OS (hazard ratio [HR] 0.66, confidence interval [CI] 0.63-0.68; P < 0.001), CSS (HR 0.56, 95% CI 0.53-0.60; P < 0.001), and SREs (HR 0.64, 95%CI 0.59-0.71; P < 0.001) when controlling for age, race, Charlson comorbidity index, prostate-specific antigen, and Gleason score.
CONCLUSION
The use of statins in men on ADT for CaP is associated with improved CSS and OS. Statins are inexpensive, well-tolerated medications that offer a promising adjunct to ADT, but require further prospective studies.
Additional Info
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The Impact of Statins in Combination With Androgen Deprivation Therapy in Patients With Advanced Prostate Cancer: A Large Observational Study
Urol. Oncol 2018 Dec 07;[EPub Ahead of Print], I Anderson-Carter, N Posielski, JI Liou, TA Khemees, TM Downs, EJ Abel, DF Jarrard, KA RichardsFrom MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
This large study, which used a very robust observational database, suggests that men on androgen-deprivation therapy (ADT) for prostate cancer taking statins have a lower risk of skeletal-related events, less chance of dying of prostate cancer, and, most impressively, substantially improved overall survival. This work mimics a prior observation from a much smaller study that use of statins at the initiation of ADT was associated with a longer time to progression.1 Although statins have been demonstrated in vitro to have antiproliferative, pro‑apoptotic and anti-invasive effects on cell lines, the more interesting potential mechanism may be their ability to decrease intracellular androgens (the fuel for prostate cancer growth) by reducing the amount of steroid precursors (in the form of cholesterol) that are available for androgen synthesis. The clinical implications of these studies are provocative, and, although the evidence is not strong enough to recommend statins in everyone, routine use in men starting ADT who also have dyslipidemia seems prudent. The observational data support the design and conduct of prospective trials to robustly test the potential benefits of statins in men with prostate cancer.
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