Guiding First-Line Treatment Decisions In Advanced Urothelial Carcinoma: A Global Survey

Abstract

Background Enfortumab vedotin combined with pembrolizumab (EV-P) has become the new standard first-line therapy for patients with advanced urothelial carcinoma (aUC), based on its superior efficacy over platinum-based chemotherapy. As this regimen is increasingly adopted in routine care, treatment decisions may often occur in sites without dedicated genitourinary oncology expertise. This global survey aimed to explore how physicians perceive clinical factors that may influence the safe and effective use of EV-P in daily practice. Material and Methods A panel of international physicians with experience in treating patients with genitourinary cancers developed a 17-question survey addressing practice settings, experience in managing aUC, and clinical considerations relevant to the use of EV-P. The participants were recruited through a network-based convenience sampling method. The responses were descriptively analyzed. Results 201 genitourinary physicians from 32 countries completed the questionnaire. The most frequently cited potential absolute contraindications were sensory or motor neuropathy grade ≥2 (64.2%), ECOG-PS ≥3 (59.2%), and non-urothelial component >50% of the tissue sample (59.2%). Other notable concerns included severe corneal/retinal abnormalities, HbA1c >11%, severe skin comorbidities, liver impairment grade ≥2, and dialysis dependence. Conclusions and relevance This survey provides practical insights into real-world physician perspectives on patient selection for EV-P. The findings highlight the need for guidance to support personalized risk assessment, facilitate early identification of patients who may require enhanced monitoring, and optimize safe integration of EV-P into clinical practice.