Impact of statins on metastatic castration-resistant prostate cancer patients receiving new hormonal agents.

[INTRODUCTION] after androgen ablation treatment for prostate cancer, virtually all patients with recurrent or advanced disease develop castration resistance (CRPC). Abiraterone and enzalutamide are the most commonly used novel antiandrogen treatments in patients with castration-resistant prostate cancer (CRPC). The solute carrier transporter (SLCO2B1) enables various anticancer compounds or hormones to enter cells, including the adrenal androgen dehydroepiandrosterone (DHEAS), a precursor to the most potent androgen dihydroxytestosterone (DHT), which is the substrate binding and activating the androgen receptor in normal and prostate cancer (PCa) cells. Other substrates of SLCO2B1 are statins. An in vitro-part study showed that statins, by binding to SLCO2B1, can block the uptake of DHEAS competitively, decreasing the available intratumoral androgen and improving and extending the effect of primary ADT.

[AIM] to evaluate whether the addition of statins to the new antiandrogens (abiraterone or enzalutamide) affects overall and progression-free survival in patients with metastatic castration-resistant prostate cancer.

[MATERIALS AND METHODS] medical records of patients with mCRPC taking abiraterone or enzalutamide between December 2019 and January 2022 were reviewed in a tertiary hospital. Patients were assessed for statin use at the time of treatment initiation, progression free (PFS) and overall survival (OS), prostate-specific antigen (PSA) variations, and other variables of interest. Statistical analysis was performed using SPSS 22.0.

[RESULTS] a total of 107 patients receiving ADT (63 abiraterone - 59.4% - and 43 enzalutamide - 40.6%) for mCRPC in this time period were eligible for inclusion in this retrospective study. Patients had a mean age of 76.5 years (48-93). 26 patients had surgery with curative intent prior to the treatment (24.5%), 19 had previous pelvic radiotherapy with curative intent (17.9%) and 20 patients (18.9%) were previously treated with chemotherapy with docetaxel. Statins use was a significant prognostic factor for longer PFS, with a mean time of 13,68 months for those who do not use statins and 19,62 months for those who do (p<0.06). No statistically significant difference was found in OS or global mortality between the patients who use or do not use statins. Statins use also did not show any difference in the reduction of PSA values during the treatment with ADT.

[CONCLUSIONS] Our study suggests a prognostic impact of statin use in the PFS in patients receiving abiraterone or enzalutamide for mCRPC. This may be related to the enhancement of the antitumor activity of the ADT drugs, but also to the cardioprotective effects associated with statin use.