Survival benefit of concurrent beta-blocker use in cancer patients treated with radiotherapy: A systematic review and meta-analysis

Clinical Snapshot

Key Findings

• P Value: Not explicitly stated in abstract; CI for OS does not cross 1.0, implying statistical significance (p < 0.05)

• Effect Size: Hazard Ratio (HR) 0.73 for OS; HR 0.69 for disease-free survival; HR 0.62 for distant metastasis-free survival

• Primary Outcome: Overall survival (OS) in cancer patients receiving radiotherapy with vs. without concurrent beta-blocker use

• Nnt Or Sensitivity: NNT not calculable from HR alone without baseline event rate data; no sensitivity/specificity applicable (therapeutic meta-analysis); no prediction interval reported

• Confidence Interval: OS: 95% CI 0.64–0.83; CIs for DFS and DMFS not reported in abstract

Clinical Application

Beta-blockers are widely available, inexpensive, and have well-characterised safety profiles. Continuation of existing BB therapy during radiotherapy is feasible and low-risk in appropriately selected patients. Initiating BBs solely for radiosensitisation is not supported by current evidence and requires prospective RCT validation. Multiple beta-blockers (metoprolol, atenolol, carvedilol, propranolol) are listed on the Australian Pharmaceutical Benefits Scheme (PBS) for cardiovascular indications at low cost. The TGA has not approved any beta-blocker for oncological indications. RACGP and Cancer Australia guidelines do not currently recommend BBs as adjunctive cancer therapy. Australian radiation oncology practice (via RANZCR) would require prospective RCT evidence before any guideline incorporation. The signal from this meta-analysis may justify inclusion of BB use as a stratification variable in future Australian cooperative group radiotherapy trials, particularly in NSCLC where the signal appears strongest. Adult patients with solid tumours (predominantly NSCLC) undergoing radiotherapy who have a concurrent indication for beta-blocker therapy (e.g., hypertension, heart failure, arrhythmia). Not currently applicable as a de novo oncological indication.

Abstract

BACKGROUND: Both preclinical and retrospective studies have implicated β-adrenergic signaling in cancer progression, leading to interest in β-blockers (BBs) as adjunctive anticancer agents. There is evidence that they may enhance the sensitivity of cancer cells to radiotherapy and other conventional therapies. We conducted a systematic review and meta-analysis to explore the radiosensitizing effects of BBs. METHODS: PubMed, the Cochrane Library, Embase, Web of Science, the China National Knowledge Infrastructure, the China biology medicine database, Wan fang Data, and the VIP database were searched for articles in both English and Chinese from the establishment of the databases to September 8, 2025, to identify studies comparing outcomes according to beta-blocker use (yes vs no) in patients with solid tumors treated with radiotherapy. The primary endpoint was overall Survival (OS), Secondary objectives included 1, 2, 5-Year Survival, disease-free survival, distant metastasis-free survival, locoregional progression-free survival and progression-free survival (PFS). RESULTS: 8 studies (3165 patients), including 7 retrospective cohort studies and 1 randomized controlled trial, were analyzed. The most common cancer was non-small cell lung cancer (n = 5). BB use was associated with significantly improved OS (hazard ratio [HR] 0.73, 95% confidence interval: 0.64-0.83). Benefits were also observed for disease-free survival (HR 0.69) and Distant Metastasis-Free Survival (HR 0.62), indicating reduced recurrence and metastasis. CONCLUSION: In this meta-analysis, the use of BBs during or around radiotherapy may be associated with longer OS in cancer patients, suggesting that it may enhance the efficacy of radiotherapy and provide a survival benefit. Alternatively, the effect of β-blockers on survival may shift from a nonspecific effect to an intriguing cancer-specific effect over time. Beta-blockers are an intriguing option to explore in prospective studies of patients with solid tumors undergoing radiotherapy.

References

1. 1.Xu, W., Xin, Y., Yang, X., Wu, M., Chen, H., Lu, X., Guo, Y., Yu, D., & Zhou, F. (2026). Survival benefit of concurrent beta-blocker use in cancer patients treated with radiotherapy: A systematic review and meta-analysis. Medicine. https://doi.org/10.1097/MD.0000000000049582