Statin Use May Increase Prostate Cancer Time to Progression After ADT Initiation

Statins may prolong time to disease progression in men who are beginning androgen deprivation therapy for advanced prostate cancer

medwireNews: Men who are taking statins when beginning androgen deprivation therapy (ADT) for hormone-sensitive prostate cancer have a significantly longer time to progression (TTP) than non-users, US researchers suggest.

After a median of 5.8 years of follow-up, TTP was a median of 27.5 months for the 283 men taking a statin at ADT initiation versus 17.4 months for the 643 patients who were not, say Philip Kantoff, from the Dana-Farber Cancer Institute in Boston, Massachusetts, and co-workers.

And the association remained significant, with a hazard ratio (HR) for TTP of 0.83 for users versus non-users, after adjusting for predefined prognostic factors, such as Gleason score, metastatic status, primary treatment, prior ADT use and prostate-specific Antigen (PSA) level at ADT initiation.

This was true for both patients who had biochemical relapse at ADT initiation (HR=0.84) and those with radiographical evidence of metastases at this point (HR=0.79), the researchers report in JAMA Oncology.

The study also includes preclinical results demonstrating that statins block uptake of the testosterone precursor dehydroepiandrosterone sulphate by competitively binding to the transporter SLCO2B1 and reducing the available intratumour androgen pool.

Noting that this “plausible mechanism” supports their clinical findings, Philip Kantoff and team conclude: “The widespread use of statins and their established safety profile make them attractive potential anticancer therapeutics as adjuvants to cytotoxic or androgen-ablating therapies.”

Evan Yu and Jorge Ramos, from the University of Washington in Seattle, USA, agree in an accompanying opinion that the study findings offer a “compelling argument” for a statin benefit in advanced prostate cancer but emphasise the need for validation in randomised trials before incorporating statin use into clinical practice.

“[A] potential clinical setting for further investigation of statins is in patients with nonmetastatic [castration-resistant prostate cancer], for whom there is no current standard of care, and in whom PSA could be evaluated in early trials as a clinical marker of response”, they suggest.

References

Harshman LC, Wang X, Nakabayashi M, et al. Statin use at the time of initiation of androgen  deprivation therapy and time to progression in patients with hormone-sensitive prostate cancer. JAMA Oncol; Advance online publication 7 May 2015. doi:10.1001/jamaoncol.2015.0829

Ramos JD, Yu EY. Progress in understanding what is being statin(ed) in prostate cancer. JAMA Oncol; Advance online publication 7 May 2015. doi:10.1001/jamaoncol.2015.0833

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