Disease progression among prostate cancer patients starting androgen deprivation therapy (ADT) was delayed by 10 months in patients already receiving statins.
Prostate cancer patients starting treatment with androgen deprivation therapy (ADT) who were already taking cholesterol-lowering statins had a 10-month prolonged time to cancer progression compared with patients who were not on statins, according to the results of a new study published in JAMA Oncology.
“Little is known about the impact of statin use and the durability of response to ADT, which is the cornerstone of treatment for metastatic hormone-sensitive prostate cancer,” wrote study authors led by Philip W. Kantoff, MD, of the Dana-Farber Cancer Institute in Boston.
In this analysis of 926 ADT-treated prostate cancer patients, 283 patients (31%) were taking a statin when ADT therapy was initiated. The median time to disease progression was 27.5 months among men taking statins, compared with 17.4 months among those who were not (P < .001). The overall median time to progression was 20.3 months for the entire cohort.
After adjusting for predefined prognostic factors, the association between statin use and longer time to disease progression remained significant. Men taking statins and ADT were 17% less likely to have disease progression compared with men who did not take a statin (P = .04). These prognostic factors included biopsy Gleason score, type of primary therapy, use of prior ADT in conjunction with localized therapy, metastatic status, and prostate-specific antigen (PSA) level at initiation of ADT.
Patients who had metastatic disease still benefited from simultaneous statin and ADT use; those with metastases had a 16% lower risk of disease progression while those with M0 disease had a 21% lower risk of disease progression.
After a median follow-up of 5.8 years, 644 patients (70%) had disease progression. Progression of disease was defined as a minimum of two increases in PSA level.
Prior studies have suggested that statin use may be linked to a lower incidence of prostate cancer, and that men who take statins have improved clinical outcomes. Statins, including atorvastatin, simvastatin, fluvastatin, and pravastatin, are inhibitors of HMG CoA reductase, a rate-limiting enzyme in the synthesis of cholesterol in the body.
The researchers also conducted in vitro studies to understand the potential molecular interactions between statins and ADT.
Both statins and precursors of androgens are substrates of the cellular transporter SLCO2B1, which functions to let different macromolecules, including hormones and anticancer compounds into cells. Prostate cancer cells increase expression of this transporter upon progression from hormone-sensitive to castration-resistant disease, and genetic variants of SLCO2B1 have been linked to duration of response with ADT. These genetic variants are thought to let in more or less androgens into prostate cancer cells.
The laboratory studies showed that statins can block the uptake of androgen precursors by competing to bind to SLCO2B1. Treatment with statins likely results in a competitive inhibition of these androgen precursors that can drive tumor growth. Statins may also have antitumor effects such as inhibiting inflammation, angiogenesis, or metastases as previous studies have suggested.
A caveat to the study is the potential effect of the ‘healthy user bias,’ noted the study authors. Men who take statins may be more likely to be healthier, because they may follow up with their physicians and see doctors regularly. A potential confounding factor in the study is the relative contribution of different types of statins on disease progression.
“The widespread use of statins and their established safety profile make them attractive potential anticancer therapeutics as adjuvants to cytotoxic or androgen-ablating therapies,” the authors concluded. Still, prospective trials are necessary to understand whether statins truly have an anti–prostate cancer role. Ten such studies are currently ongoing.