medwireNews: Men with advanced prostate cancer may derive a significant survival benefit from the concurrent use of statins alongside androgen-ablative therapies, suggest the Canadian authors of a systematic review and meta-analysis.
The risk for overall mortality was a significant 27% lower among men who did versus did not use statins after diagnosis, while the prostate cancer-specific mortality (PCSM) risk was reduced by a significant 35% with statin use, they report in JAMA Network Open.
The researchers point out that there was “significant interstudy heterogeneity” for both estimates, but they say: “It is worth noting, however, that although variability remained considerable, the differences were between small and large protective associations; in other words, these findings appear to accurately support a statin benefit, although they may be restricted by imprecision.”
Moreover, “[t]hese findings were not driven by any single cohort, withstood robust sensitivity analyses, and were free of publication bias,” writes the team.
The results come from a meta-analysis that included 19 publications reporting data from 25 retrospective cohorts comprising 119,878 individuals receiving either androgen deprivation therapy (ADT) or androgen receptor axis-targeted therapies (ARATs). Just over half (55%) were taking statins while undergoing androgen ablation.
The majority (n=16) of the cohorts included men with newly diagnosed hormone-sensitive disease; overall mortality was reported in 19 cohorts and PCSM in 14.
Subgroup analyses showed that statin use appeared to reduce the PCSM risk by a greater degree among men who received ARATs than those given ADT, with respective hazard ratios relative to nonuse of statins of 0.40 and 0.68.
However, there was no such difference by type of androgen-ablative therapy for overall mortality, say Robert Hamilton (University of Toronto, Ontario) and co-investigators.
Discussing the potential mechanisms for the observed association between statin use and reduced mortality risk, the team speculates that “[s]tatins may inhibit inflammation, angiogenesis, cell proliferation, migration, adhesion, invasion, and promotion of apoptosis by disruption of cellular communication mechanisms.”
It is also possible that “a synergistic effect among statins, reduction of cholesterol levels, and androgen-ablative therapies may play a role,” add Hamilton and colleagues.
And they continue: “Last, it is established that androgen-ablative therapies increase cardiometabolic risk by promoting visceral obesity, dyslipidemia, and dysglycemia. Statins may work to negate some of the adverse cardiometabolic effects of androgen-ablative therapies, contributing to a survival benefit.”
In conclusion, the researchers say that “[t]hese results contribute to our understanding of the associations between prostate cancer, the androgen axis, and statins and provide high-quality evidence supporting a chemopreventive role for statins in prostate cancer.”
But “the use of retrospective data and unexplained heterogeneity lower our confidence in directly incorporating these findings into clinical practice,” and therefore, “randomized clinical trials are warranted to confirm these findings,” they write.
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