Highlights
- •Statins are potential candidates for secondary prevention in metastatic prostate cancer.
- •Atorvastatin, pravastatin, and rosuvastatin demonstrated greater survival benefits than other types of statins.
Abstract
Objectives
Before launching large clinical trials to confirm the effects of statins in improving
outcomes among men with prostate cancer (PC), the most appropriate target patient
population and the type of statins need to be clearly identified.
Patients and methods
A retrospective cohort study was conducted using the Taiwan Cancer Registry of 2008–2014.
This study included 5749 men with locally advanced and metastatic PC who received
only androgen deprivation therapy (ADT) in the first year after their cancer diagnosis.
Statin users were defined as anyone who was prescribed statins for >28 days. An inverse
probability of treatment-weighted Cox model was used to estimate the effects of statin
use on all-cause mortality and PC-specific mortality (PCSM) while treating the statin
status as a time-dependent variable.
Results
Overall, 2259 patients died, and 1495 of them died of PC during a median follow-up
of 3.6 years from 1 year after their diagnosis. Statin use was associated with significant
reductions in all-cause mortality (hazard ratio [HR] = 0.78, 95% confidence interval
[CI]: 0.70–0.86) and PCSM (HR = 0.76, 95% CI: 0.68–0.86) for metastatic disease and
all-cause mortality (HR = 0.66, 95% CI: 0.54–0.81) for locally advanced disease. Patients
who received atorvastatin, pravastatin, rosuvastatin or pitavastatin showed a stronger
reduction in mortality than those who received other statins. Benefits of statins
were consistently observed in men who received post-diagnostic statins, even in those
with high comorbidities or an old age.
Conclusions
Our results suggest that only atorvastatin, pravastatin and rosuvastatin were associated
with improved survival in advanced PC patients receiving ADT.
Keywords
To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to European Journal of CancerAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- Chemohormonal therapy in metastatic hormone-sensitive prostate cancer.N Engl J Med. 2015; 373: 737-746
- Abiraterone in metastatic prostate cancer.N Engl J Med. 2017; 377: 1696-1697
- Abiraterone for prostate cancer not previously treated with hormone therapy.N Engl J Med. 2017; 377: 338-351
- Docetaxel plus prednisone or mitoxantrone plus prednisone for advanced prostate cancer: updated survival in the TAX 327 study.J Clin Oncol. 2008; 26: 242-245
- Prednisone plus cabazitaxel or mitoxantrone for metastatic castration-resistant prostate cancer progressing after docetaxel treatment: a randomised open-label trial.Lancet. 2010; 376: 1147-1154
- Use of statins and the risk of death in patients with prostate cancer.J Clin Oncol. 2014; 32: 5-11
- Postdiagnosis statin use and mortality in Danish patients with prostate cancer.J Clin Oncol. 2017; 35: 3290-3297
- Association between statins and clinical outcomes among men with prostate cancer: a systematic review and meta-analysis.Prostate Cancer Prostatic Dis. 2016; 19: 151-162
- Quality assessment and improvement of nationwide cancer registration system in Taiwan: a review.Jpn J Clin Oncol. 2015; 45: 291-296
- A 10-year experience with universal health insurance in Taiwan: measuring changes in health and health disparity.Ann Intern Med. 2008; 148: 258-267
- Threats to validity of nonrandomized studies of postdiagnosis exposures on cancer recurrence and survival.J Natl Cancer Inst. 2013; 105: 1456-1462
- Application of lag-time into exposure definitions to control for protopathic bias.Pharmacoepidemiol Drug Saf. 2007; 16: 250-258
- Manual for staging of cancer.5th ed. JB Lippincott, Philadelphia1997
- The influence of cardiovascular morbidity on the prognosis in prostate cancer. Experience from a 12-year nationwide Danish population-based cohort study.BMC Canc. 2011; 11: 519
- Chemical, pharmacokinetic and pharmacodynamic properties of statins: an update.Fundam Clin Pharmacol. 2005; 19: 117-125
- Marginal structural models and causal inference in epidemiology.Epidemiology. 2000; 11: 550-560
- A proportional hazards model for the subdistribution of a competing risk.J Am Stat Assoc. 1999; 94: 496-509
- Statin drugs and risk of advanced prostate cancer.J Natl Cancer Inst. 2006; 98: 1819-1825
- Statin use at the time of initiation of androgen deprivation therapy and time to progression in patients with hormone-sensitive prostate cancer.JAMA Oncol. 2015; 1: 495-504
- Effects of statin use on the response duration to androgen deprivation therapy in metastatic prostate cancer.Korean J Urol. 2015; 56: 630-636
- Associations between statin use and progression in men with prostate cancer treated with primary androgen deprivation therapy.Scand J Urol. 2017; 51: 464-469
- Abiraterone plus prednisone in metastatic, castration-sensitive prostate cancer.N Engl J Med. 2017; 377: 352-360
- Addition of docetaxel, zoledronic acid, or both to first-line long-term hormone therapy in prostate cancer (STAMPEDE): survival results from an adaptive, multiarm, multistage, platform randomised controlled trial.Lancet. 2016; 387: 1163-1177
- Lovastatin-mediated G1 arrest is through inhibition of the proteasome, independent of hydroxymethyl glutaryl-CoA reductase.Proc Natl Acad Sci U S A. 1999; 96: 7797-7802
- The statins as anticancer agents.Clin Cancer Res. 2003; 9: 10-19
- HMG-CoA reductase inhibitors and the malignant cell: the statin family of drugs as triggers of tumor-specific apoptosis.Leukemia. 2002; 16: 508-519
- Comparison of the efficacy and safety of rosuvastatin versus atorvastatin, simvastatin, and pravastatin across doses (STELLAR* Trial).Am J Cardiol. 2003; 92: 152-160
- Treating patients with documented atherosclerosis to National Cholesterol Education Program-recommended low-density-lipoprotein cholesterol goals with atorvastatin, fluvastatin, lovastatin and simvastatin.J Am Coll Cardiol. 1998; 32: 665-672
- Impact of circulating cholesterol levels on growth and intratumoral androgen concentration of prostate tumors.PLoS One. 2012; 7 (e30062)
- Statins and cancer prevention.Nat Rev Canc. 2005; 5: 930-942
- The HMG-CoA reductase inhibitor, atorvastatin, promotes a Th2 bias and reverses paralysis in central nervous system autoimmune disease.Nature. 2002; 420: 78-84
- Statin induces apoptosis and cell growth arrest in prostate cancer cells.Cancer Epidemiol Biomark Prev. 2008; 17: 88-94
- Pharmacological actions of statins: a critical appraisal in the management of cancer.Pharmacol Rev. 2012; 64: 102-146
- Statin use and risk of prostate cancer: a Danish population-based case-control study, 1997-2010.Cancer Epidemiol. 2014; 38: 42-47
- Statin use and prostate cancer risk in a large population-based setting.Cancer Causes Control. 2008; 19: 767-774
- Statin use and risk of prostate cancer: results from a population-based epidemiologic study.Am J Epidemiol. 2008; 168: 250-260
- Statins and prostate cancer risk: a case-control study.Am J Epidemiol. 2005; 162: 318-325
- Statin use and prostate cancer survival in the Finnish randomized study of screening for prostate cancer.Eur Urol Focus. 2017; 3: 212-220
- Executive_Yuan_of_Republic_of_China_(Taiwan). Yearbook. 2016: 10-11
- International prevalence, recognition, and treatment of cardiovascular risk factors in outpatients with atherothrombosis.Jama. 2006; 295: 180-189
Article Info
Publication History
Published online: March 01, 2019
Accepted:
November 27,
2018
Received in revised form:
November 19,
2018
Received:
August 17,
2018
Identification
Copyright
© 2019 Elsevier Ltd. All rights reserved.
ScienceDirect
Access this article on ScienceDirectLinked Article
- Prostate cancer incidence and mortality among men using statins and non-statin lipid-lowering medicationsEuropean Journal of CancerVol. 112
- PreviewStatins have demonstrated protection against aggressive/late-stage and/or lethal prostate cancer (PC), but prior studies are limited by small populations, short follow-up and unequal health-care access. Research has not demonstrated that non-statin lipid-lowering medications (NSLLMs) provide a similar benefit, which would support a cholesterol-based mechanism. We sought to rigorously test the hypothesis that cholesterol-lowering drugs affect PC incidence and severity.
- Full-Text
- Preview
- Statins – No more cream for cancerEuropean Journal of CancerVol. 112
- PreviewIn this issue of the European Journal of Cancer, Shao et al. and Van Rompay et al. [1,2] report that statins and, in the latter manuscript, also non-statin lipid-lowering medications appear to improve prostate cancer outcomes, both by retrospective analyses. This adds to the large body of epidemiological studies suggesting a favourable role for statins on the clinical outcomes of men with prostate cancer, but the precise nature of the anticancer effect of these drugs remains controversial. Retrospective studies have an inherent bias because all these men received the statin (or any other lipid-lowering drug) for a medical condition that may influence their prognosis or receiving a statin could be a surrogate for being under more ‘intensive’ medical care.
- Full-Text
- Preview
