Predictive role of ABC transporters in the efficacy of enfortumab vedotin for urothelial carcinoma

To evaluate the correlation between ATP-binding cassette (ABC) transporter expression and therapeutic efficacy of enfortumab vedotin (EV), an antibody-drug conjugate targeting Nectin-4, in urothelial cancer, as only a few studies have been conducted on this topic.ObjectiveTo evaluate the correlation between ATP-binding cassette (ABC) transporter expression and therapeutic efficacy of enfortumab vedotin (EV), an antibody-drug conjugate targeting Nectin-4, in urothelial cancer, as only a few studies have been conducted on this topic.This retrospective study included 20 patients with metastatic urothelial carcinoma (mUC), including bladder and upper urinary tract cancers, who were treated with EV at Dokkyo Medical University Hospital between 2022 and 2024. Immunohistochemical staining was performed on formalin-fixed, paraffin-embedded tissue samples. Progression-free survival (PFS) was estimated using the Kaplan-Meier method, and differences between subgroups (e.g., Nectin-4 and ABC transporter expression) were compared using the log-rank test.Patients and methodsThis retrospective study included 20 patients with metastatic urothelial carcinoma (mUC), including bladder and upper urinary tract cancers, who were treated with EV at Dokkyo Medical University Hospital between 2022 and 2024. Immunohistochemical staining was performed on formalin-fixed, paraffin-embedded tissue samples. Progression-free survival (PFS) was estimated using the Kaplan-Meier method, and differences between subgroups (e.g., Nectin-4 and ABC transporter expression) were compared using the log-rank test.Immunohistochemical analysis indicated that tumours with high ABC transporter expression exhibited shorter PFS time and poorer response to EV. Furthermore, a decrease in Nectin-4 expression and an increase in ABC transporter expression were observed as the disease progressed from non-muscle-invasive to muscle-invasive and metastatic. Patients with Nectin-4-positive and ABC transporter-negative tumours had the longest PFS, underscoring the prognostic significance of these biomarkers.ResultsImmunohistochemical analysis indicated that tumours with high ABC transporter expression exhibited shorter PFS time and poorer response to EV. Furthermore, a decrease in Nectin-4 expression and an increase in ABC transporter expression were observed as the disease progressed from non-muscle-invasive to muscle-invasive and metastatic. Patients with Nectin-4-positive and ABC transporter-negative tumours had