Kijima Toshiki, Takada-Owada Atsuko, Shimoda Hiroki, Kokubun Hidetoshi, Uematsu Toshitaka, Takei Kohei, Betsunoh Hironori, Yashi Masahiro, Ishida Kazuyuki, Kamai Takao
Department of Urology Dokkyo Medical University Tochigi Japan.
Department of Diagnostic Pathology Dokkyo Medical University Tochigi Japan.
BJUI Compass. 2025 Jan 11;6(1):e488. doi: 10.1002/bco2.488. eCollection 2025 Jan.
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.
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.
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.
To our knowledge, this study is the first to show a correlation between ABC transporter expression and EV efficacy in urothelial carcinoma. Future research should focus on optimizing treatment strategies based on Nectin-4 and ABC transporter expression to improve outcomes.
评估三磷酸腺苷结合盒（ABC）转运蛋白表达与靶向Nectin-4的抗体药物偶联物恩杂鲁胺（EV）在尿路上皮癌中的治疗效果之间的相关性，因为关于这一主题的研究较少。
这项回顾性研究纳入了20例转移性尿路上皮癌（mUC）患者，包括膀胱癌和上尿路癌，这些患者于2022年至2024年在独协医科大学医院接受了EV治疗。对福尔马林固定、石蜡包埋的组织样本进行免疫组织化学染色。采用Kaplan-Meier法估计无进展生存期（PFS），并使用对数秩检验比较亚组之间的差异（例如，Nectin-4和ABC转运蛋白表达）。
免疫组织化学分析表明，ABC转运蛋白高表达的肿瘤表现出较短的PFS时间和对EV较差的反应。此外，随着疾病从非肌层浸润性发展到肌层浸润性和转移性，观察到Nectin-4表达降低和ABC转运蛋白表达增加。Nectin-4阳性且ABC转运蛋白阴性的肿瘤患者的PFS最长，突出了这些生物标志物的预后意义。
据我们所知，本研究首次表明ABC转运蛋白表达与尿路上皮癌中EV疗效之间存在相关性。未来的研究应集中在基于Nectin-4和ABC转运蛋白表达优化治疗策略以改善治疗结果。
