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 signalling 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 PRISMA guidelines using a predefined (PICO) framework. Four databases (PubMed, Embase, Cochrane Library, and Web of Science) were searched. Eligible studies compared beta-blocker users with non-users and reported survival outcomes in patients with solid cancer. Outcomes included overall survival (OS), cancer-specific survival (CSS), disease-free survival (DFS), progression-free survival (PFS) and recurrence-free survival (RFS). Risk of bias was assessed using the Newcastle-Ottawa Scale (NOS) and the Cochrane Risk of Bias 2 tool. Certainty of evidence was evaluated using GRADE. 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 significantly improved OS (HR 0.88, 95% CI: 0.80-0.96) and PFS (HR 0.82, 95%CI: 0.69-0.97). The greatest effects on OS were observed in patients with gastrointestinal (HR 0.84, 95%CI: 0.72-0.98), lung (HR 0.84, 95%CI: 0.71-0.99), and skin cancers (HR 0.81, 95%CI: 0.73-0.89). Effects appeared stronger with post-diagnostic 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 OS and PFS in patients with solid cancers.