Urinary Extracellular Vesicle–Associated EphA2 Predicts Intravesical Recurrence in Bladder Cancer

ABSTRACT Objective To examine the clinical usefulness of EphA2 detected on urinary extracellular vesicles (uEphA2) for bladder cancer detection and for estimating the risk of intravesical recurrence after transurethral resection of bladder tumor (TURBT). Methods An enzyme‐linked immunosorbent assay was established to measure EphA2‐positive urinary extracellular vesicles. The diagnostic cohort comprised 191 participants, including 120 patients with bladder cancer and 71 controls. Results uEphA2 concentrations were higher in patients with bladder cancer than in controls. Receiver operating characteristic analysis yielded an area under the curve of 0.679, with 46.7% sensitivity and 87.3% specificity. Among patients evaluable for post‐TURBT recurrence, high uEphA2 levels were associated with shorter intravesical recurrence‐free survival. This association remained significant in multivariable Cox regression analysis after adjustment for the EORTC risk score and age. Conclusions uEphA2 showed modest diagnostic accuracy but high specificity and was independently associated with intravesical recurrence. These results support its potential use as a non‐invasive urinary marker for post‐TURBT risk stratification.