Beta-Blocker Use and Survival Outcomes in Pancreatic Cancer Patients: A Systematic Review and Meta-Analysis.

[BACKGROUND] Pancreatic cancers (PCs)-especially pancreatic ductal adenocarcinoma (PDAC)-are among the deadliest digestive system cancers, with a 5 year survival of approximately 13%. Beta blockers (BBs), which inhibit beta-adrenergic receptor-mediated angiogenesis and immunosuppression, are potential candidates for oncological drug repurposing. However, the clinical evidence is inconsistent, and robust subgroup analyses are lacking. This study systematically evaluated the association between BB use and survival in PC patients. Furthermore, subgroup analyses were conducted to clarify differential clinical effects.

[METHODS] This study was conducted in accordance with PRISMA guidelines and registered with PROSPERO (CRD420251106076). The PubMed, Embase, Cochrane Library, and Web of Science databases were searched to identify observational studies on all-cause mortality (ACM) and cancer-specific mortality (CSM). Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using RevMan 5.3 and R, and the results were presented in forest plots.

[RESULTS] This analysis included nine retrospective cohort studies involving over 30 000 patients. There were no significant associations between BB use and ACM (HR = 1.07; 95% CI [0.95-1.20]) or CSM (HR = 0.89; 95% CI [0.70-1.14]). However, subgroup analysis revealed that BB use was significantly associated with increased ACM risk in surgical patients (HR = 1.18; 95% CI [1.05-1.31]). Moreover, non-selective BB (NSBB) use significantly reduced CSM risk (HR = 0.81; 95% CI [0.68-0.97]). Both sensitivity and trim-and-fill analyses confirmed the robustness and consistency of these results.

[CONCLUSIONS] This meta-analysis presents the first systematic evidence regarding the potential role of NSBBs in mitigating CSM, thus providing support for their potential repurposing. In addition, these findings indicate that perioperative BB use may be associated with increased ACM risk, highlighting the need for careful perioperative risk assessment. To further substantiate these findings, future prospective studies should explore combined approaches, particularly those integrating immune or anti-angiogenic therapies.