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Database of Abstracts of Reviews of Effects (DARE): Quality-assessed Reviews [Internet].

Statin use and risk of prostate cancer: a meta-analysis of observational studies

D Bansal, K Undela, S D'Cruz, and F Schifano.

Review published: 2012.

CRD summary

The authors concluded that statins reduced the risk of both total prostate cancer and clinically important advanced prostate cancer. Possible small study bias and the presence of significant statistical and clinical variation make the reliability of the authors’ conclusion uncertain.

Authors' objectives

To examine statin use in relation to the risk of total prostate cancer and advanced prostate cancer.

Searching

PubMed database was searched up to February 2012 for studies published in English. Search terms were reported. Bibliographies and citations of retrieved articles were scanned.

Study selection

Observational studies (cohort or case-control) that evaluated exposure to statins and risk of prostate cancer were eligible. Reviews, letters to the editor without original data, editorial and case reports were excluded.

Studies were published between 1993 to 2011 and most were conducted in USA and Europe. Most studies assessed prostate cancer diagnosis through cancer registries. All studies were controlled for potential confounding factors by matching or adjustment. Most studies evaluated exposure specifically to statins and the risk of prostate cancer.

Two reviewers independently selected studies for inclusion. Any discrepancies were resolved by joint re-evaluation of the original article.

Assessment of study quality

Study quality was assessed using the Newcastle Ottawa scale which included selection, comparability and outcome for cohort or exposure for case-control. Studies with a total score of 9 were considered to be good quality.

Two reviewers independently evaluated study quality. Any disagreements were resolved by involvement of a third reviewer.

Data extraction

Data were extracted to calculate relative risks (RRs) and associated 95% confidence intervals (CI). The relative risk estimates that reflected the greatest degree of control for potential confounders were extracted.

Two reviewers independently extracted data.

Methods of synthesis

Meta-analysis was performed to calculate pooled risk ratios and 95% CI. A random-effects model (DerSimonian and Laird) was used where there was evidence of heterogeneity; otherwise a fixed-effect model was used. The Cochrane Q test and the Ι² statistic were used to assess heterogeneity; Ι²>50% and Q statistic p<0.10 were considered statistically significant for heterogeneity. Publication bias was assessed using Begg and Mazumdar adjusted correlation test and Egger regression asymmetry test.

Subgroup analyses were performed according to study design, adjustment for prostate specific antigen testing, adjustment for body mass index (BMI) and/or adverse lifestyle and studies before and after the Bonovas et al. analysis (a systematic review on the same topic that included randomised controlled trials and observational studies published in 2008). Sensitivity analysis was assessed by excluding one study at a time. Cumulative meta-analysis was performed to identify the change in trend of reporting risk over time.

Results of the review

Twenty-seven studies (15 cohort and 12 case-control studies) were included in the review (1,893,571 male participants). All cohort studies scored 8 in Newcastle Ottawa scale and with case-control studies the total score was 7.7. Follow-up ranged from two years to 17 years.

The meta-analysis showed that use of statins significantly reduced the risk of both total prostate cancer (RR 0.93, 95% CI 0.87 to 0.99; Ι²=82%; 26 studies) and advanced prostate cancer (RR 0.80, 95% CI 0.70–0.90; Ι²=38%; seven studies). Also the results showed that long term use of statin (five years and more) did not significantly affect the risk of total prostate cancer.

Subgroup analyses showed no significant difference between different study designs and whether or not studies were adjusted for prostate specific antigen testing; however, there was a significant association of statin use and reduced risk of prostate cancer for the studies adjusted for BMI and/or adverse life style and the studies published after Bonovas et al. Sensitivity analysis confirmed the stability of results. Cumulative meta-analysis showed a change in trend of reporting risk from positive to negative in statin users between 1993 and 2011.

Authors' conclusions

The meta-analysis supported the hypothesis that statins reduced the risk of both total prostate cancer and clinically important advanced prostate cancer.

CRD commentary

The review addressed a clear question and was supported by appropriate inclusion criteria. The authors searched only one database. The searches were restricted to published studies in English so publication and language bias could not be ruled out. Publication bias was investigated and none was observed. Attempts were made to minimise reviewer bias and errors in the review process. Appropriate criteria were used to assess study quality.

Substantial heterogeneity was identified and potential causes were explored by subgroup and sensitivity analyses. There was potential for small study bias to have affected the results as smaller studies showed greater effects than larger studies. The authors noted limitations of the review in terms of publication and language bias, variations in study design, confounder adjustments, definitions of drug exposure and long-term statin use.

Possible small study bias and the presence of significant statistical and clinical variation make the reliability of the authors’ conclusion uncertain.

Implications of the review for practice and research

Practice: The authors did not state any implications for practice.

Research: The authors stated that further studies were needed to confirm that statins reduced the risk of prostate cancer and identify the underlying biological mechanisms.

Funding

No funding.

Bibliographic details

Bansal D, Undela K, D'Cruz S, Schifano F. Statin use and risk of prostate cancer: a meta-analysis of observational studies. PLOS ONE 2012; 7(10): e46691. [PMC free article: PMC3462187] [PubMed: 23049713]

Indexing Status

Subject indexing assigned by NLM

MeSH

Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors /pharmacology; Male; Models, Statistical; Prostatic Neoplasms /epidemiology /prevention & control; Risk Assessment; Sensitivity and Specificity; Treatment Outcome

AccessionNumber

12012046899

Database entry date

04/06/2013

Record Status

This is a critical abstract of a systematic review that meets the criteria for inclusion on DARE. Each critical abstract contains a brief summary of the review methods, results and conclusions followed by a detailed critical assessment on the reliability of the review and the conclusions drawn.

CRD has determined that this article meets the DARE scientific quality criteria for a systematic review.

Copyright © 2014 University of York.

PMID: 23049713