Abstract CT133: Atorvastatin and prostate cancer - a phase 2 clinical trial
Authors: Murtola Teemu J. , Riikonen Jarno , Syvälä Heimo , Tolonen Teemu , Koskimäki Juha , Pakarainen Tomi , Kaipia Antti , Isotalo Taina , Kujala Paula , Tammela Teuvo 
Published: July 2017

Abstract
Background: Use of cholesterol-lowering statin drugs has been linked to lowered risk of advanced prostate cancer (PCa) and improved PCa-specific survival. However, statins’ efficacy against specifically against PCa has not been tested in a prospective randomized clinical trial.
Materials and methods: A total of 160 men with PCa and scheduled for radical prostatectomy were randomly allocated 1:1 to receive either 80 mg atorvastatin or placebo from recruitment to surgery. The study inclusion criteria included 1) histologically confirmed adenocarcinoma of the prostate, 2) radical prostatectomy selected as the first-line treatment and 3) signing of informed consent. Exclusion criteria were 1) previous oncological treatments 2) previous usage statins, finasteride or dutasteride within a year of inclusion, 3) clinically significant liver or kidney insufficiency, 4) previous adverse effects from cholesterol-lowering drugs and 5) use of drugs that might interact with statins Serum PSA was measured at recruitment and at the time of surgery. After prostatectomy, intraprostatic inflammation was quantified according to international consensus criteria. PSA change, calculated by subtracting PSA value at recruitment from PSA before prostatectomy, was compared between the trial arms using Man-Whitney U test. Extent and amount of intraprostatic inflammation were compared using linear regression and ANOVA. Separate comparisons were made for inflammation in glandular, periglandular and stromal compartments as well as for combined inflammation score. All analyses were performed for all cases combined, and separately for low-grade (prostatectomy Gleason score 3+4 or lower) and high-grade (Gleason score 4+3 or higher) cases.
Results: In total 160 men were recruited and randomized. Of these 158 completed the follow-up. Median time from recruitment to surgery was four weeks. Compliance to assigned treatment was excellent, 96%. Four men in the atorvastatin arm, none in the placebo arm discontinued the study drug due to side effects. They were analyzed in their assigned study arm according to the intention-to-treat principle. Overall, the median PSA change after the intervention did not differ between the atorvastatin and placebo arms (median change -0.4; IQR -1.4-0.1 and -0.2; IQR -1.1-0.4 in the atorvastatin and placebo arm, respectively), p for interaction 0.150. However, among the high-grade cases (n=35), PSA decreased among all men in the atorvastatin arm (median change -0.6, IQR -2[[Unsupported Character - Codename &shy;]]- -0.2), but not in the placebo arm (median change 0, IQR -0.6-0.4); p for interaction 0.024. Overall, intraprostatic inflammation score did not differ between the study arms (p for difference 0.772). Result was similar for separate tissue compartments.
Conclusions: Short-term high-dose atorvastatin therapy before radical prostatectomy lowers serum PSA values in high-grade cases but not in low-grade cases, indicating that atorvastatin intervention affects the prostate in such cases. Future clinical trials testing statins in prostate cancer patients should aim to enroll patients with Gleason score at least 4+3.
Citation Format: Teemu J. Murtola, Jarno Riikonen, Heimo Syvälä, Teemu Tolonen, Juha Koskimäki, Tomi Pakarainen, Antti Kaipia, Taina Isotalo, Paula Kujala, Teuvo Tammela. Atorvastatin and prostate cancer - a phase 2 clinical trial [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr CT133. doi:10.1158/1538-7445.AM2017-CT133