Affiliation:
1. Department of Biomedical Sciences, Humanitas University Pieve Emanuele Milan Italy
2. Department of Urology, IRCCS Humanitas Research Hospital Rozzano Milan Italy
3. Department of Urology APHM, North Academic Hospital Marseille France
4. Department of Urology, Fundació Puigvert Autonoma University of Barcelona Barcelona Spain
5. Department of Urology Medical University of Silesia Zabrze Poland
6. Department of Urology La Croix du Sud Hôpital Quint Fonsegrives France
Abstract
AbstractBackgroundPreclinical studies have shown that the sympathetic nervous system is involved in the development of metastases, suggesting a potential antitumor effect of beta‐blockers. These findings sparked a controversy over the past decade regarding the direction of the association between beta‐blocker use and prostate cancer (PCa) mortality. To investigate this association, we conducted a systematic review and meta‐analysis.MethodsThe review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta‐analyses guidelines to identify eligible studies. The primary outcome was PCa mortality in beta‐blocker users versus nonusers, and overall survival was studied as a secondary endpoint. We assessed heterogeneity using the Cochrane Q test and quantified it using I2 values. In the case of heterogeneity (Cochrane Q test p < 0.05 and I2 > 50%), random‐effect models were used to determine the association between beta‐blockers use and survival outcomes.ResultsTen studies met our inclusion criteria and a total of 74,970 patients were included: 26,674 beta‐blocker users and 48,326 nonusers.There was no statistically significant association between beta‐blocker exposure and PCa mortality (hazard ratio [HR] 0.97; 95% confidence interval [CI] 0.87–1.09; p = 0.61). However, significant heterogeneity was found. Meta‐regression analysis to explain heterogeneity showed no effect of any of the variables assessed (country, percentage of beta‐blocker users, type of beta‐blocker [selective and nonselective], study period, PCa stage and follow‐up duration; all p > 0.05). We found similar results when we restricted the analysis to studies that include only patients with advanced PCa (HR 0.92; 95% CI 0.80–1.06; p = 0.24). Similarly, we found no association with overall survival (HR 1.02; 95% CI 0.94–1.10; p = 0.64). Meta‐regression analysis was also performed, but none of the variables assessed explained the observed heterogeneity (all p > 0.05).ConclusionsWe found no association between beta‐blockers use and overall survival or PCa mortality. This meta‐analysis, which includes a considerable population and the most recent literature, provides important data for routine clinical care and patient counseling.