Atorvastatin Versus Placebo for Prostate Cancer Before Radical Prostatectomy-A Randomized, Double-blind, Placebo-controlled Clinical Trial

Eur Urol. 2018 Dec;74(6):697-701. doi: 10.1016/j.eururo.2018.06.037. Epub 2018 Jul 18.

Abstract

We tested whether intervention with atorvastatin affects the prostate beneficially compared with placebo in men with prostate cancer in a randomized clinical trial. A total of 160 statin-naïve prostate cancer patients scheduled for radical prostatectomy were randomized to use 80mg atorvastatin or placebo daily from recruitment to surgery for a median of 27 d. Blinding was maintained throughout the trial. In total, 158 men completed the follow-up, with 96% compliance. Overall, atorvastatin did not significantly lower tumor proliferation index Ki-67 or serum prostate-specific antigen (PSA) compared with placebo. In subgroup analyses, after a minimum of 28 d of atorvastatin use, Ki-67 was 14.1% lower compared with placebo (p = 0.056). Among high-grade cases (International Society of Urological Pathology Gleason grade 3 or higher), atorvastatin lowered PSA compared with placebo: median change -0.6 ng/ml; p = 0.024. Intraprostatic inflammation did not differ between the study arms (p = 0.8). Despite a negative overall result showing no effect of statins on Ki67 or PSA overall, in post hoc exploratory analyses, there appeared to be benefit after a minimum duration of 28 d. Further studies are needed to verify this. PATIENT SUMMARY: Cholesterol-lowering atorvastatin does not lower prostate cancer proliferation rate compared with placebo overall, but exploratory analyses suggest a benefit in longer exposure.

Keywords: Atorvastatin; Clinical trial; Inflammation; Ki-67; Prostate cancer; Prostate-specific antigen.

Publication types

  • Comparative Study
  • Letter
  • Pragmatic Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Antineoplastic Agents / administration & dosage*
  • Antineoplastic Agents / adverse effects
  • Atorvastatin / administration & dosage*
  • Atorvastatin / adverse effects
  • Cell Proliferation / drug effects
  • Chemotherapy, Adjuvant
  • Double-Blind Method
  • Finland
  • Humans
  • Kallikreins / blood
  • Ki-67 Antigen / metabolism
  • Male
  • Middle Aged
  • Neoadjuvant Therapy*
  • Prostate-Specific Antigen / blood
  • Prostatectomy / methods*
  • Prostatic Neoplasms / blood
  • Prostatic Neoplasms / drug therapy*
  • Prostatic Neoplasms / pathology
  • Prostatic Neoplasms / surgery
  • Time Factors
  • Treatment Outcome

Substances

  • Antineoplastic Agents
  • Ki-67 Antigen
  • MKI67 protein, human
  • Atorvastatin
  • KLK3 protein, human
  • Kallikreins
  • Prostate-Specific Antigen