Six-factor-based stratification system for enfortumab vedotin monotherapy in pre-treated patients with metastatic or locally advanced urothelial carcinoma

PURPOSE: This study aimed to identify prognostic factors and develop a prognostic stratification system for progression-free survival (PFS) and overall survival (OS) in patients with locally advanced or metastatic urothelial carcinoma (la/m UC) treated with enfortumab vedotin (EV). METHODS: We retrospectively analyzed 387 patients with la/m UC who received EV monotherapy and evaluated the prognostic factors using the Cox proportional hazards regression model. We then used the significant factors to derive a system for predicting prognosis. RESULTS: The median PFS and OS were 7.6 and 14.6 months, respectively. Multivariable analysis revealed six significant factors common to both PFS and OS: poor Eastern Cooperative Oncology Group performance status (≥ 1), presence of aberrant histology (histological subtypes or divergent differentiation), presence of bone metastasis, anemia (hemoglobin < 10 g/dL), high C-reactive protein levels (> 0.5 mg/dL), and hypercalcemia (corrected calcium > 10.2 mg/dL). Based on the number of positive factors, patients were categorized into three groups: 147 patients with none or one factor (low-risk group), 92 patients with two factors (intermediate-risk group), and 148 patients with three or more factors (high-risk group). The log-rank test indicated significant differences in both PFS and OS among the three groups, with C-indices of 0.634 and 0.700 for PFS and OS, respectively. CONCLUSIONS: Six factors were identified as common prognostic factors for both PFS and OS in la/m UC patients receiving EV monotherapy. The newly developed prognostic risk stratification system based on these factors is clinically useful, particularly for predicting OS.