Introduction & Objectives:
This systematic review and meta-analysis investigates the potential role of beta-blockers in cutaneous melanoma management. Beta-adrenoceptors are upregulated in cancers, including melanoma, and beta-blockers – have been shown to inhibit angiogenesis and tumour cell migration in pre-clinical models. However, clinical evidence for their use in modulating melanoma patients’ outcomes remains sparse.
Materials & Methods:
Our PRISMA-adherent meta-analysis included eleven independent cohorts across twelve articles, comprising 4904 beta-blocker users and 16678 non-users. Primary outcomes included disease-free (DFS), recurrence-free (RFS), melanoma-specific (MSS), and overall survival (OS). The main effect size was the adjusted hazard ratio (aHR) with 95% confidence interval. Risk of bias was assessed using the Cochrane ROBINS-I tool. Nine cohorts included Cox regression models and were included in the random effects pooled meta-analysis.
Results:
No significant associations were found between beta-blocker use and either MSS or OS, though we identified a trend favouring the use of specifically pan-selective beta-blockers compared to cardio-selective blockers. A remarkable beneficial association was found with DFS; however, we approach these results cautiously as they were all retrieved from studies by the same group. The study designs were largely observational and varied in disease stage, beta-blocker selectivity, and timeframe. In modern practice, most beta-blocker prescriptions are cardio-selective, which may have obscured the benefit of pan-selective beta-blockers in this meta-analysis.
Conclusion:
Our findings do not demonstrate a survival advantage for beta-blocker use in cutaneous melanoma. However, there is preliminary evidence that pan-selective beta-blockers specifically may be protective, and this should be investigated via randomised controlled trials. Future prognostic studies should delineate exposure by beta-blocker type and consider adjustments for competing risks and immortal time bias if applicable.