Febuxostat Versus Allopurinol for Prevention of Tumor Lysis Syndrome: A Systematic Review and Integrated Frequentist–Bayesian Meta-analysis

Background: Effective control of serum uric acid (UA) is clinically essential in the prevention of tumor lysis syndrome (TLS), as it is closely associated with the risk of TLS and related renal complications. Both allopurinol and febuxostat are widely used as standard urate-lowering prophylactic agents. However, direct comparative data on their efficacy and safety for TLS prevention are limited and require systematic investigation. Aim: This study aimed to conduct a comprehensive systematic review and meta-analysis to evaluate the efficacy and safety of febuxostat compared with allopurinol for the prevention of TLS in patients with malignancies. Methods: A systematic review and meta-analysis were conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. PubMed, Embase, and the Cochrane Library were searched through August 2025 for comparative studies evaluating febuxostat versus allopurinol in cancer patients at risk for TLS. Primary outcomes included TLS incidence, serum UA area under the curve (AUC), UA control rate, and drug-related adverse effects. Data were synthesized using random-effects models in both frequentist and Bayesian statistical frameworks. Risk of bias (ROB) was assessed with ROB 2.0 and ROB in nonrandomized studies of intervention tools. Results: Six studies (three randomized controlled trials [RCTs] and three cohort studies; total n = 945) were included in this study. Frequentist analysis showed no significant difference in TLS incidence between febuxostat and allopurinol (odds ratio [OR] = 0.88, 95% confidence interval [CI] = 0.51–1.53). Bayesian analysis confirmed substantial uncertainty (posterior median OR = 0.86, 95% credible intervals [CrI] = 0.37–2.00). For UA AUC and control rate, both methods indicated inconclusive benefits, particularly in the presence of high study heterogeneity. Febuxostat was associated with fewer drug-related adverse effects by frequentist analysis (OR = 0.46, 95% CI = 0.22–0.99); Bayesian results suggested a likely but not definitive safety advantage (OR = 0.46, 95% CrI = 0.19–1.20). Conclusion: Febuxostat may have modest safety advantages over allopurinol in TLS prevention, but the current evidence is limited and characterized by considerable uncertainty, especially when assessed with Bayesian methods. Larger, high-quality RCTs are necessary to establish clear clinical recommendations for TLS prophylaxis.