Impact of beta-blockers on prognostic outcomes in solid cancers: a systematic review and meta-analysis

BACKGROUND: Beta-blockers are conventionally prescribed for cardiovascular indications and have potential for repurposing in oncology as adrenergic signaling promotes cancer progression. This systematic review and meta-analysis evaluated whether beta-blocker use is associated with improved survival outcomes in patients with all stages of solid cancer. METHODS: This systematic review and meta-analysis was conducted in accordance with the Preferred Reporting Items for Systemic Reviews and Meta-Analyses (PRISMA) guidelines using a predefined (participants, intervention, comparator, and outcome) framework. Four databases (PubMed, Embase, Cochrane Library, and Web of Science) were searched. Eligible studies compared beta-blocker users with nonusers and reported survival outcomes in patients with solid cancer. Outcomes included overall survival, cancer-specific survival, disease-free survival, progression-free survival, and recurrence-free survival. Risk of bias was assessed using the Newcastle-Ottawa Scale and the Cochrane Risk of Bias 2 tool. Certainty of evidence was evaluated using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. RESULTS: A total of 5122 articles were screened; 94 articles were included in the systematic review and 84 in the meta-analysis comprising 603 827 patients. Beta-blocker use in patients with solid cancers was associated with statistically improved overall survival (hazard ratio [HR] = 0.88, 95% confidence interval [CI] = 0.80 to 0.96) and progression-free survival (HR = 0.82, 95% CI = 0.69 to 0.97). The greatest effects on overall survival were observed in patients with gastrointestinal (HR = 0.84, 95% CI = 0.72 to 0.98), lung (HR = 0.84, 95% CI = 0.71 to 0.99), and skin cancers (HR = 0.81, 95% CI = 0.73 to 0.89). Effects appeared stronger with postdiagnostic exposure, and in certain cancer subtypes, however, heterogeneity and the observational nature of most included studies warrant cautious interpretation. CONCLUSION: Beta-blocker use was associated with improved overall and progression-free survival in patients with solid cancers.