The association between beta-blockers use and prostate cancer mortality: A mini systematic review and meta-analysis

Preclinical 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.

The 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.

Ten 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).

We 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.