Safety of tranexamic acid in patients with stage III melanoma undergoing lymph node dissection: a retrospective cohort study

Tranexamic acid (TXA) is widely used off-label and increasingly explored for drug repurposing as an anticancer agent within melanoma surgery, mandating safety evaluation from existing data. Although TXA is safe in surgical populations, its safety profile has not been specifically evaluated in melanoma surgery. Concerns arise from preclinical models suggesting that antifibrinolytic therapy may facilitate micrometastatic spread. Other drug-related adverse effects, such as thromboembolic events and seizure risk, must also be considered in this context. This study evaluates the safety of perioperative TXA in melanoma surgery. Patients ( n = 155) with stage III cutaneous melanoma undergoing complete lymph node dissection at Aarhus and Aalborg University Hospital between 1 May 2020 and 31 July 2024, were identified, and clinical data were extracted retrospectively. Outcomes included recurrence (local, regional or systemic), thromboembolic events, and seizures. Recurrences were analyzed using a cause-specific Cox proportional hazards model, adjusting for age and adjuvant therapy. Fisher's exact test was used to compare metastatic patterns by recurrence location (local, regional, or systemic), thromboembolic events, and seizures between groups. Among 155 patients, 44 (28%) were exposed to TXA. Recurrences were recorded in 87 patients (56%), with similar proportions across exposure groups. TXA was not associated with recurrence (hazard ratio 0.94, 95% confidence interval: 0.57-1.54), nor with differences in the metastatic pattern. No association between risk of thromboembolic events or seizure and TXA exposure was detected. Perioperative TXA is not associated with recurrence, thromboembolic events, or seizures in patients with stage III melanoma undergoing complete lymph node dissection.