PD42-07 INDEPENDENT EXPRESSION OF PROGRAMMED DEATH LIGAND 1 FROM NECTIN-4 IN UPPER TRACT UROTHELIAL CARCINOMA

Abstract

You have accessJournal of UrologyBladder Cancer: Basic Research & Pathophysiology II (PD42)1 Sep 2021PD42-07 INDEPENDENT EXPRESSION OF PROGRAMMED DEATH LIGAND 1 FROM NECTIN-4 IN UPPER TRACT UROTHELIAL CARCINOMA Kazutoshi Fujita, Eisuke Tomiyama, Diana Taheri, Maria Rodriguez Pena, Eri Banno, Taigo Kato, Koji Hatano, Atsunari Kawashima, Takeshi Ujike, Motohide Uemura, Tetsuya Takao, Seiji Yamaguchi, Hiroaki Fushimi, Kazuhiro Yoshimura, Hirotsugu Uemura, George Netto, and Norio Nonomura Kazutoshi FujitaKazutoshi Fujita More articles by this author , Eisuke TomiyamaEisuke Tomiyama More articles by this author , Diana TaheriDiana Taheri More articles by this author , Maria Rodriguez PenaMaria Rodriguez Pena More articles by this author , Eri BannoEri Banno More articles by this author , Taigo KatoTaigo Kato More articles by this author , Koji HatanoKoji Hatano More articles by this author , Atsunari KawashimaAtsunari Kawashima More articles by this author , Takeshi UjikeTakeshi Ujike More articles by this author , Motohide UemuraMotohide Uemura More articles by this author , Tetsuya TakaoTetsuya Takao More articles by this author , Seiji YamaguchiSeiji Yamaguchi More articles by this author , Hiroaki FushimiHiroaki Fushimi More articles by this author , Kazuhiro YoshimuraKazuhiro Yoshimura More articles by this author , Hirotsugu UemuraHirotsugu Uemura More articles by this author , George NettoGeorge Netto More articles by this author , and Norio NonomuraNorio Nonomura More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002056.07AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Locally advanced or metastatic upper tract urothelial carcinoma (UTUC) is a lethal disease with limited treatment options for patients who do not positively respond to platinum chemotherapy and/or immune checkpoint inhibitor. Enfortumab vedotin is a novel antibody–drug conjugate targeting Nectin-4, which is highly expressed in urothelial carcinoma. However, the expression status of Nectin-4 in UTUC remains unclear. The relationship between Nectin-4 and Programmed Death Ligand 1 (PD-L1) in UTUC is also unclear. In the present study, we investigated the expression of Nectin-4 in UTUC using tissue microarray (TMA) specimens of patients with UTUC as well as the association between Nectin-4 protein expression and clinicopathological features or outcomes. We also examined PD-L1 expression and its correlation with that of Nectin-4. METHODS: UTUC TMA was constructed with spotted triplicate urothelial tumour samples (from dominant tumours/invasive components if present) and paired normal-appearing urothelial tissues (from the renal pelvis and ureter) obtained from 99 patients with non-metastatic UTUC, who underwent radical nephroureterectomy performed at Osaka General Medical Center. We performed immunohistochemical analysis of 99 UTUC tissue microarray with anti-PDL1 and anti-Nectin-4 antibody. RESULTS: Nectin-4-positivity was detected in 65 (65.7%) samples, which was significantly higher than that in non-neoplastic urothelium (p<0.001). Expression of PD-L1 was detected in 24 (24.2%) samples, and there was no correlation between the expression of Nectin-4 and PD-L1. Patients with strong Nectin-4 expressing tumours had a significantly higher risk of tumour progression (p=0.031) and cancer-specific mortality (p=0.036). Strong Nectin-4 expression was also an independent predictor of tumour progression in the high-risk group (pT3 ≤ or presence of lymphovascular invasion or lymph node metastasis) (Hazard ratio, 3.32 [95% confidence interval, 1.20–7.98; p=0.027]). CONCLUSIONS: We demonstrated that Nectin-4 expression rate in UTUC was 65.7% and independent of PD-L1 expression. Strong expression of Nectin-4 was associated with poor prognosis in UTUC. These findings suggested that enfortumab vedotin may be effective in a broad range of patients with UTUC regardless of the PD-L1 expression level. Source of Funding: None © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e727-e727 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Kazutoshi Fujita More articles by this author Eisuke Tomiyama More articles by this author Diana Taheri More articles by this author Maria Rodriguez Pena More articles by this author Eri Banno More articles by this author Taigo Kato More articles by this author Koji Hatano More articles by this author Atsunari Kawashima More articles by this author Takeshi Ujike More articles by this author Motohide Uemura More articles by this author Tetsuya Takao More articles by this author Seiji Yamaguchi More articles by this author Hiroaki Fushimi More articles by this author Kazuhiro Yoshimura More articles by this author Hirotsugu Uemura More articles by this author George Netto More articles by this author Norio Nonomura More articles by this author Expand All Advertisement Loading ...