TY - JOUR
T1 - The Association Between Statin Use and Outcomes in Patients Initiating Androgen Deprivation Therapy
AU - Hamilton, Robert J.
AU - Ding, Keyue
AU - Crook, Juanita M.
AU - O'Callaghan, Christopher J.
AU - Higano, Celestia S.
AU - Dearnaley, David P.
AU - Horwitz, Eric M.
AU - Goldenberg, S. Larry
AU - Gospodarowicz, Mary K.
AU - Klotz, Laurence
N1 - Copyright © 2020. Published by Elsevier B.V.
PY - 2021/4
Y1 - 2021/4
N2 - BACKGROUND: Studies have conflicting results regarding the association between statin use and biochemical recurrence for prostate cancer (PCa). A limited number of studies examining statins in advanced stages report positive results, with a few specifically examining statins and androgen deprivation therapy (ADT).OBJECTIVE: To perform a post hoc secondary analysis of a randomised controlled trial (RCT) of men initiating ADT to examine the association between statin use and outcomes.DESIGN, SETTING, AND PARTICIPANTS: Patients with prostate-specific antigen (PSA) >3 ng/ml >1 yr following primary/salvage radiotherapy were enrolled in an RCT of intermittent androgen deprivation (IAD) versus continuous ADT (NCT00003653). Baseline and on-study statin use was modelled as a time-dependent covariate.OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary endpoint was overall survival. Models were adjusted for age, time from radiotherapy to ADT, baseline PSA, and prior ADT.RESULTS AND LIMITATIONS: Of 1364 patients, statin users (585; 43%) were younger (72.7 vs 73.8 yr, p = 0.001) and less likely to have PSA >15 ng/ml (20% vs 25%, p = 0.04). After a median follow-up of 6.9 yr, statin use was associated with reduced overall (hazard ratio [HR]: 0.64; 95% confidence interval [CI] 0.53-0.78, p < 0.001) and PCa-specific (HR: 0.65, 95% CI 0.48-0.87, p = 0.004) mortality. Statin users had 13% longer time to castration resistance, but this did not reach statistical significance (p = 0.15). As an exploratory endpoint, in the IAD arm, statin users had longer time off treatment (median: 0.85 vs 0.64 yr, p = 0.06). Limitations include potential for residual confounding between statin users and nonusers, and confounding by indication.CONCLUSIONS: In men treated with ADT following primary or salvage radiotherapy, statin use was associated with improved overall and PCa-specific survival. In patients treated with IAD, statin use was associated with a trend towards longer time off treatment. A prospective trial of statins in men commencing ADT is warranted.PATIENT SUMMARY: We found a favourable association between statin use and survival outcomes in patients initiating androgen deprivation therapy.
AB - BACKGROUND: Studies have conflicting results regarding the association between statin use and biochemical recurrence for prostate cancer (PCa). A limited number of studies examining statins in advanced stages report positive results, with a few specifically examining statins and androgen deprivation therapy (ADT).OBJECTIVE: To perform a post hoc secondary analysis of a randomised controlled trial (RCT) of men initiating ADT to examine the association between statin use and outcomes.DESIGN, SETTING, AND PARTICIPANTS: Patients with prostate-specific antigen (PSA) >3 ng/ml >1 yr following primary/salvage radiotherapy were enrolled in an RCT of intermittent androgen deprivation (IAD) versus continuous ADT (NCT00003653). Baseline and on-study statin use was modelled as a time-dependent covariate.OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary endpoint was overall survival. Models were adjusted for age, time from radiotherapy to ADT, baseline PSA, and prior ADT.RESULTS AND LIMITATIONS: Of 1364 patients, statin users (585; 43%) were younger (72.7 vs 73.8 yr, p = 0.001) and less likely to have PSA >15 ng/ml (20% vs 25%, p = 0.04). After a median follow-up of 6.9 yr, statin use was associated with reduced overall (hazard ratio [HR]: 0.64; 95% confidence interval [CI] 0.53-0.78, p < 0.001) and PCa-specific (HR: 0.65, 95% CI 0.48-0.87, p = 0.004) mortality. Statin users had 13% longer time to castration resistance, but this did not reach statistical significance (p = 0.15). As an exploratory endpoint, in the IAD arm, statin users had longer time off treatment (median: 0.85 vs 0.64 yr, p = 0.06). Limitations include potential for residual confounding between statin users and nonusers, and confounding by indication.CONCLUSIONS: In men treated with ADT following primary or salvage radiotherapy, statin use was associated with improved overall and PCa-specific survival. In patients treated with IAD, statin use was associated with a trend towards longer time off treatment. A prospective trial of statins in men commencing ADT is warranted.PATIENT SUMMARY: We found a favourable association between statin use and survival outcomes in patients initiating androgen deprivation therapy.
KW - Androgen Antagonists/adverse effects
KW - Androgens
KW - Humans
KW - Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use
KW - Male
KW - Prostate-Specific Antigen
KW - Prostatic Neoplasms/drug therapy
UR - http://www.scopus.com/inward/record.url?scp=85098555808&partnerID=8YFLogxK
U2 - 10.1016/j.eururo.2020.12.031
DO - 10.1016/j.eururo.2020.12.031
M3 - Article
C2 - 33390282
AN - SCOPUS:85098555808
SN - 0302-2838
VL - 79
SP - 446
EP - 452
JO - European Urology
JF - European Urology
IS - 4
ER -
