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Introduction: Radical cystectomy (RC) is associated with substantial blood loss and high perioperative blood transfusion (PBT) rates, which may negatively affect outcomes. Tranexamic acid (TXA) reduces bleeding in various surgical settings, but evidence on its efficacy and safety in RC is limited and inconsistent. We aimed to systematically evaluate the impact of TXA on perioperative transfusion rates and thromboembolic risk in patients undergoing RC.

Method: A systematic search of CENTRAL, PubMed, Embase, and Web of Science (up to January 2025) was performed. RCTs and observational studies assessing TXA in RC were eligible. Data were pooled using random-effects meta-analysis. Primary outcome was overall PBT. Secondary outcomes included intraoperative transfusion, estimated blood loss (EBL), and venous thromboembolism (VTE). Risk of bias was assessed using RoB-2 and ROBINS-I; certainty of evidence was evaluated using GRADE.

Results: Four studies (1 RCT, 3 observational studies) were included. TXA significantly reduced overall PBT (OR 0.48, 95% CI 0.27–0.82; p=0.008); however, this effect was driven by observational studies. The single RCT showed no significant reduction in transfusion rates (OR 0.75, 95% CI 0.20–2.84; p=0.67), suggesting potential confounding in non-randomized data. EBL was numerically lower with TXA (MD −37 mL, 95% CI −78 to 5; p=0.08). TXA was not associated with increased VTE risk (OR 1.49, 95% CI 0.86–2.57; p=0.16). Evidence certainty was moderate, limited by heterogeneity and predominantly retrospective data.

Conclusion: TXA appears to reduce perioperative transfusion requirements in RC without increasing thromboembolic risk, though evidence from randomized trials remains inconclusive. Further RCTs are warranted to confirm efficacy, standardize dosing protocols, and evaluate outcomes in minimally invasive RC.