Sex-Specific Differences in Disease-Free, Progression-Free and Overall Survival Following Enfortumab Vedotin Therapy for Advanced or Metastatic Urothelial Cancer: A Systematic Review and Meta-analysis.

Women have poorer survival rates in advanced, metastatic, or muscle-invasive bladder cancer (MIBC) than men. Enfortumab vedotin (EV) has changed the therapy and outcomes of MIBC and advanced bladder cancer dramatically. Therefore, the primary aim of this systematic review and meta-analysis was to evaluate sex-specific differences in disease-free (DFS), progression-free (PFS), cancer-specific survival (CSS), event-free survival (EFS), and overall survival (OS) in those patients. In October 2025, we performed a systematic literature search using MEDLINE via PubMed, Embase, and Cochrane Library. This study was prospectively registered at PROSPERO (CRD420251064260). The detailed review protocol is accessible via CRD. The systematic literature search identified 249 studies, of which 17 fulfilled the inclusion criteria. No significant sex-specific difference was observed for OS (10 studies; hazard ratio [HR] 0.88; 95% confidence interval [CI], 0.73-1.06; P = .17; I² = 32%). For PFS (8 studies), female sex was associated with a significantly better outcome (HR 0.67; 95% CI, 0.57-0.78; P < .001; I² = 0%). Because the funnel plot suggested a significant publication bias, we conducted adjustment analyses, which yielded an HR of 0.41 (95% CI, 0.24-0.57; P < .001). Only limited data were available for DFS, CSS, and EFS. Overall, the risk of bias was assessed as moderate. There is very limited evidence that women have a significantly better PFS than men during treatment with EV for bladder cancer. Further studies should incorporate explicit sex-specific analyses, eg, hormonal levels or genetic aspects, which are needed.