The Suggested Unique Association Between the Various Statin Subgroups and Prostate Cancer

Hanan Goldberg; Faizan K Mohsin; Refik Saskin; Girish S Kulkarni; Alejandro Berlin; Miran Kenk; Christopher J D Wallis; Zachary Klaassen; Thenappan Chandrasekar; Ardalan E Ahmad; Rashid K Sayyid; Olli Saarela; Linda Penn; Shabbir M H Alibhai; Neil Fleshner

doi:10.1016/j.euf.2020.06.005

The Suggested Unique Association Between the Various Statin Subgroups and Prostate Cancer

Eur Urol Focus. 2021 May;7(3):537-545. doi: 10.1016/j.euf.2020.06.005. Epub 2020 Jun 30.

Authors

Affiliations

¹ Division of Urology, Department of Surgical Oncology, Princess Margaret Cancer Centre, University Health Network and the University of Toronto, Toronto, ON, Canada; Institute of Medical Science, University of Toronto, Toronto, ON, Canada; Department of Urology, SUNY Upstate Medical University, Syracuse, NY, USA; Institute for Clinical Evaluative Sciences, Toronto, ON, Canada. Electronic address: gohanan@gmail.com.
² Dalla Lana School of Public Health, University of Toronto, Toronto, ON, Canada.
³ Institute for Clinical Evaluative Sciences, Toronto, ON, Canada.
⁴ Division of Urology, Department of Surgical Oncology, Princess Margaret Cancer Centre, University Health Network and the University of Toronto, Toronto, ON, Canada; Institute for Clinical Evaluative Sciences, Toronto, ON, Canada.
⁵ Radiation Medicine Program, Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada; Department of Radiation Oncology, University of Toronto, Toronto, ON, Canada; Techna Institute, University Health Network, Toronto, ON, Canada.
⁶ Division of Urology, Department of Surgical Oncology, Princess Margaret Cancer Centre, University Health Network and the University of Toronto, Toronto, ON, Canada.
⁷ Division of Urology, Department of Surgical Oncology, Princess Margaret Cancer Centre, University Health Network and the University of Toronto, Toronto, ON, Canada; Department of Urology, Vanderbilt University Medical Center, Nashville, TN, USA.
⁸ Division of Urology, Department of Surgery, Medical College of Georgia, Augusta University, Augusta, GA, USA; Georgia Cancer Center, Augusta, GA, USA.
⁹ Department of Urology, Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia PA, USA.
¹⁰ Division of Urology, Department of Surgical Oncology, Princess Margaret Cancer Centre, University Health Network and the University of Toronto, Toronto, ON, Canada; Institute of Medical Science, University of Toronto, Toronto, ON, Canada.
¹¹ Division of Urology, Department of Surgery, Medical College of Georgia, Augusta University, Augusta, GA, USA.
¹² Department of Medical Biophysics, University of Toronto, Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.
¹³ Institute of Medical Science, University of Toronto, Toronto, ON, Canada; Department of Medicine, University Health Network and University of Toronto, Toronto, ON, Canada.

PMID: 32620539
DOI: 10.1016/j.euf.2020.06.005

Abstract

Background: The chemopreventive effect of various medications in prostate cancer (PCa) has gained interest. Specifically, the potential impact of statins on PCa incidence has been studied, but solely as a "drug family" overlooking the distinctive pharmacological properties of its two main subgroups: hydrophilic and hydrophobic statins.

Objective: To assess the impact of statin subgroups on PCa-specific mortality (PCSM), PCa diagnosis, and undergoing another prostate biopsy.

Design, setting, and participants: This is a population-based cohort study in Ontario identifying all men aged ≥66 yr with a history of a single negative prostate biopsy (representing healthy men at risk for PCa) between 1994 and 2016, who were not on any of the analyzed medications prior to the study, with a median follow-up of 9.42 yr (interquartile range 8.03 yr).

Outcome measurements and statistical analysis: Using multivariable cause-specific hazard models with time-dependent covariates, the association of hydrophobic and hydrophilic statins with all study outcomes was analyzed. Other putative chemopreventive medications (including alpha-blockers, 5-alpha-reductase inhibitors, and proton-pump inhibitors), age, rurality, comorbidities, and study inclusion year were included in the models.

Results and limitations: Overall, 21 512 men were identified. Statins were taken by 11 401 patients (50.3%), 5184 men (24.1%) were diagnosed with PCa, and 805 (3.7%) died from it. Overall, 7556 patients (35.1%) underwent another biopsy. Any use of hydrophilic statins was associated with a 32.4% (95% confidence interval [CI] 12.9-47.5%), a 20% (95% CI 10-28%), and an 18% (95% CI 6.1-27.3%) decreased risk of PCSM, undergoing another prostate biopsy, and being diagnosed with PCa, respectively. Hydrophobic statins were associated with 17% (95% CI 2-31%) decreased PCSM. The study is limited by its retrospective nature, selection bias, and accompanying health-administrative database inaccuracies.

Conclusions: Use of any statin may be associated with a lower hazard of PCSM, with hydrophilic statins showing a greater association with decreased PCa diagnosis rates. Preferentially prescribing one statin subgroup over another in men needs further exploration.

Patient summary: Use of any statin may be associated with a lower probability of dying from prostate cancer. Hydrophilic statins (rosuvastatin and pravastatin) may also be more positively associated with a lower risk of undergoing an additional prostate biopsy and being diagnosed with prostate cancer in men aged ≥66 yr.

Keywords: Hydrophilic statins; Hydrophobic statins; Prostate biopsy; Prostate cancer; Prostate cancer–specific survival.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Cohort Studies
Humans
Hydroxymethylglutaryl-CoA Reductase Inhibitors* / therapeutic use
Male
Prostate / pathology
Prostatic Neoplasms* / diagnosis
Retrospective Studies

Substances

Hydroxymethylglutaryl-CoA Reductase Inhibitors