1. Conferences Overview
    2. 71. Kongress der Nordrhein-Westfälischen Gesellschaft für Urologie
    3. NECTIN4 amplification is a frequent event in central nervous system metastases of urothelial carcinoma
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71. Kongress der Nordrhein-Westfälischen Gesellschaft für Urologie

Nordrhein-Westfälische Gesellschaft für Urologie e. V.
16.-17.04.2026
Essen

Meeting Abstract

NECTIN4 amplification is a frequent event in central nervous system metastases of urothelial carcinoma

Richard Weiten - University Hospital Cologne, Germany, Department of Urology, Uro-Oncology, Robot-Assisted and Specialized Urologic Surgery, Cologne, Deutschland
Constantin Rieger - University Hospital Cologne, Germany, Department of Urology, Uro-Oncology, Robot-Assisted and Specialized Urologic Surgery, Cologne, Deutschland
Julian Heidenreich - University Hospital Cologne, Germany, Department of Urology, Uro-Oncology, Robot-Assisted and Specialized Urologic Surgery, Cologne, Deutschland
Yuri Tolkach - University Hospital Cologne, Germany, Institute of Pathology, Cologne, Deutschland
Thomas Stehle - University Hospital Cologne, Germany, Institute of Neuropathology, Cologne, Deutschland
Florian Schmid - University Hospital Cologne, Germany, Department of Urology, Uro-Oncology, Robot-Assisted and Specialized Urologic Surgery, Cologne, Deutschland; University Hospital Zurich, Department of Urology, Zurich, Schweiz
Teresa Schmidt - University Hospital Essen, Division of Clinical Neuro-Oncology, Department of Neurology and Center for Translational Neuro- and Behavioral Sciences (C-TNBS), Essen, Deutschland
Martin Glase - St. Marien Hospital, Department of Neurology and Neurooncology, Lünen, Deutschland; University Hospital Bonn, University of Bonn, Department of Neurooncology, Center for Neurology, Bonn, Deutschland
Tobias Blau - University Hospital Essen, Institute of Neuropathology, Essen, Deutschland
Kathy Keyvani - University Hospital Essen, Institute of Neuropathology, Essen, Deutschland
Thomas Büttner - University Hospital Bonn, Department of Urology and Paediatric Urology, Bonn, Deutschland
Viktor Grünwald - University Hospital Essen, Clinic for Internal Medicine (Tumor Research) and Clinic for Urology, Interdisciplinary Genitourinary Oncology at the West-German Cancer Center, Essen, Deutschland
Michael Hölzel - University Hospital Bonn, Institute of Experimental Oncology, Bonn, Deutschland
Axel Heidenreich - University Hospital Cologne, Germany, Department of Urology, Uro-Oncology, Robot-Assisted and Specialized Urologic Surgery, Cologne, Deutschland
Markus Eckstein - University Hospital Erlangen, Institute of Pathology , Erlangen, Deutschland
Niklas Klümper - University Hospital Bonn, Department of Urology and Paediatric Urology, Bonn, Deutschland; University Hospital Bonn, Institute of Experimental Oncology, Bonn, Deutschland

Text

Introduction & objectives: NECTIN4 amplification has emerged as a promising biomarker for predicting response to targeted anti-NECTIN4 therapies in metastatic urothelial carcinoma (mUC), triple-negative breast cancer (TNBC), and non-small cell lung cancer (NSCLC). The anti-NECTIN4 antibody-drug conjugate enfortumab vedotin (EV), combined with pembrolizumab (EV/P), is now standard care for mUC. However, data on its effectiveness in patients with active central nervous system (CNS) metastases (MET) are limited, as these patients were excluded from pivotal trials. Recent studies show that NECTIN4 amplification is frequent in mUC (about 15–25%) and predicts response to EV and survival benefits. Furthermore, NECTIN4 amplification appears to be a stable genomic event during metastasis progression. This study aimed to characterize NECTIN4 amplification and protein expression specifically in CNS metastases of mUC compared with extracranial metastatic sites.

Materials & methods: NECTIN4 gene amplification was assessed by fluorescence in situ hybridization (FISH), and tumors with a NECTIN4/CEN1 ratio ≥ 2.0 were classified as amplified. NECTIN4 protein expression was evaluated by immunohistochemistry (H-score). Statistical analyses were performed using nonparametric tests (Chi-square, Mann-Whitney U).

Results: In our CNS MET cohort (n = 18), compared to previous comprehensive mUC cohorts (1: non-CNS mUC, n = 128; 2: EV-treated mUC, n = 108), NECTIN4 gene amplification was found in 66.7% of CNS MET cases (12/18), which is significantly higher than the 26% observed in the EV-treated cohort at baseline (28/108; Chi-square test, p = 0.0016). Additionally, CNS MET showed higher membranous NECTIN4 expression (median H-score 175, IQR 88–260) compared to non-CNS mUC (median H-score 40, IQR 0–140; p < 0.0001).

Conclusion: In conclusion, NECTIN4 amplification is highly prevalent in CNS MET from UC. These results provide a strong biological rationale for extending the use of NECTIN4-targeted therapies such as EV to patients with brain MET.