{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,17]],"date-time":"2026-02-17T00:07:52Z","timestamp":1771286872877,"version":"3.50.1"},"reference-count":36,"publisher":"Georg Thieme Verlag KG","issue":"01","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Aktuelle Urol"],"published-print":{"date-parts":[[2026,2]]},"abstract":"<jats:title>Zusammenfassung<\/jats:title>\n                  <jats:p>Die Therapie des metastasierten Urothelkarzinoms (mUC) wurde viele Jahrzehnte durch platinhaltige Chemotherapien dominiert. Sp\u00e4testens mit der Einf\u00fchrung von Immuncheckpoint-Inhibitoren, insbesondere in Kombination mit modernen Antik\u00f6rper-Wirkstoff-Konjugaten (ADC) und FGFR3-Inhibitoren, wurde dieser Therapiestandard in einigen Indikationen \u00fcberholt. Dennoch kommen biomarkergesteuerte Therapieentscheidungen bislang selten zum Einsatz. Die bislang verf\u00fcgbaren Biomarker helfen allerdings bislang auch nur in vereinzelten Therapiesituationen. F\u00fcr ADCs k\u00f6nnte sich dies allerdings bei einer hohen Expressionsvariabilit\u00e4t verschiedener Targets wie NECTIN-4, Her2neu, EGFR und TROP2 substanziell ver\u00e4ndern. Das Vorhandensein von aktivierenden FGFR3-Mutationen oder -Fusionen er\u00f6ffnet zudem eine klar definierte, wenn auch kleine therapeutische Nische, die unter Umst\u00e4nden in Zukunft f\u00fcr lokalisierte Stadien des Urothelkarzinoms gr\u00f6\u00dfer werden k\u00f6nnte. Um diese therapeutischen Neuerungen in Zukunft zielgerecht und pr\u00e4zise steuern und einsetzen zu k\u00f6nnen, wird eine Biomarkerstratifizierung von Tumoren in Zukunft vermutlich abdingbar werden. Die aktuellen Entwicklungen stellen somit ein gro\u00dfes Potenzial f\u00fcr eine echte Pr\u00e4zisionsonkologie dar.<\/jats:p>","DOI":"10.1055\/a-2622-6243","type":"journal-article","created":{"date-parts":[[2025,7,1]],"date-time":"2025-07-01T19:34:38Z","timestamp":1751398478000},"page":"46-51","source":"Crossref","is-referenced-by-count":0,"title":["Gegenw\u00e4rtige und zuk\u00fcnftige Therapiestratifizierung des metastasierten Urothelkarzinoms: eine gro\u00dfe Chance f\u00fcr eine echte Pr\u00e4zisionsonkologie"],"prefix":"10.1055","volume":"57","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6929-8691","authenticated-orcid":false,"given":"G\u00fcnter","family":"Niegisch","sequence":"first","affiliation":[{"name":"Department of Urology, Heinrich-Heine-Universitat Dusseldorf, Dusseldorf, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stefanie","family":"Zsch\u00e4bitz","sequence":"first","affiliation":[{"name":"Oncology, DKFZ, Heidelberg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Niklas","family":"Kl\u00fcmper","sequence":"first","affiliation":[{"name":"Department of Urology, University Hospital Bonn, Bonn, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Markus","family":"Eckstein","sequence":"first","affiliation":[{"name":"Institute of Pathology, Friedrich-Alexander-Universitat Erlangen-Nurnberg, Erlangen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"194","published-online":{"date-parts":[[2025,7,1]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"2432","DOI":"10.1200\/JCO.2011.34.8433","article-title":"Treatment of patients with metastatic urothelial cancer \"unfit\" for Cisplatin-based chemotherapy","volume":"29","author":"MD Galsky","year":"2011","journal-title":"J Clin Oncol"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"265","DOI":"10.1007\/s00120-022-01760-4","article-title":"Metastatic urothelial carcinoma-guideline-based therapy and new options","volume":"61","author":"G Niegisch","year":"2022","journal-title":"Urologe A"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"2446","DOI":"10.1200\/JCO.23.01983","article-title":"NECTIN4 Amplification Is Frequent in Solid Tumors and Predicts Enfortumab Vedotin Response in Metastatic Urothelial Cancer","volume":"42","author":"N Klumper","year":"2024","journal-title":"J Clin Oncol"},{"key":"ref4","doi-asserted-by":"publisher","first-page":"1961","DOI":"10.1056\/NEJMoa2308849","article-title":"Erdafitinib or Chemotherapy in Advanced or Metastatic Urothelial Carcinoma","volume":"389","author":"Y Loriot","year":"2023","journal-title":"N Engl J Med"},{"key":"ref5","doi-asserted-by":"publisher","first-page":"2102","DOI":"10.1056\/NEJMoa2034442","article-title":"Adjuvant Nivolumab versus Placebo in Muscle-Invasive Urothelial Carcinoma","volume":"384","author":"DF Bajorin","year":"2021","journal-title":"N Engl J Med"},{"key":"ref6","doi-asserted-by":"publisher","first-page":"1778","DOI":"10.1056\/NEJMoa2309863","article-title":"Nivolumab plus Gemcitabine-Cisplatin in Advanced Urothelial Carcinoma","volume":"389","author":"MS van der Heijden","year":"2023","journal-title":"N Engl J Med"},{"key":"ref7","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1016\/S0140-6736(16)32455-2","article-title":"Atezolizumab as first-line treatment in cisplatin-ineligible patients with locally advanced and metastatic urothelial carcinoma: a single-arm, multicentre, phase 2 trial","volume":"389","author":"AV Balar","year":"2017","journal-title":"Lancet"},{"key":"ref8","doi-asserted-by":"publisher","first-page":"1015","DOI":"10.1056\/NEJMoa1613683","article-title":"Pembrolizumab as Second-Line Therapy for Advanced Urothelial Carcinoma","volume":"376","author":"J Bellmunt","year":"2017","journal-title":"N Engl J Med"},{"key":"ref9","doi-asserted-by":"publisher","first-page":"748","DOI":"10.1016\/S0140-6736(17)33297-X","article-title":"Atezolizumab versus chemotherapy in patients with platinum-treated locally advanced or metastatic urothelial carcinoma (IMvigor211): a multicentre, open-label, phase 3 randomised controlled trial","volume":"391","author":"T Powles","year":"2018","journal-title":"Lancet"},{"key":"ref10","doi-asserted-by":"publisher","first-page":"1547","DOI":"10.1016\/S0140-6736(20)30230-0","article-title":"Atezolizumab with or without chemotherapy in metastatic urothelial cancer (IMvigor130): a multicentre, randomised, placebo-controlled phase 3 trial","volume":"395","author":"MD Galsky","year":"2020","journal-title":"Lancet"},{"key":"ref11","doi-asserted-by":"publisher","first-page":"931","DOI":"10.1016\/S1470-2045(21)00152-2","article-title":"Pembrolizumab alone or combined with chemotherapy versus chemotherapy as first-line therapy for advanced urothelial carcinoma (KEYNOTE-361): a randomised, open-label, phase 3 trial","volume":"22","author":"T Powles","year":"2021","journal-title":"Lancet Oncol"},{"key":"ref12","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1056\/NEJMoa2401726","article-title":"Adjuvant Pembrolizumab versus Observation in Muscle-Invasive Urothelial Carcinoma","volume":"392","author":"AB Apolo","year":"2025","journal-title":"N Engl J Med"},{"key":"ref13","doi-asserted-by":"publisher","first-page":"1773","DOI":"10.1056\/NEJMoa2408154","article-title":"Perioperative Durvalumab with Neoadjuvant Chemotherapy in Operable Bladder Cancer","volume":"391","author":"T Powles","year":"2024","journal-title":"N Engl J Med"},{"key":"ref14","doi-asserted-by":"publisher","first-page":"133","DOI":"10.1016\/j.eururo.2022.10.020","article-title":"Spatial Immunephenotypes of Distant Metastases but not Matched Primary Urothelial Carcinomas Predict Response to Immune Checkpoint Inhibition","volume":"83","author":"F Erlmeier","year":"2023","journal-title":"Eur Urol"},{"key":"ref15","doi-asserted-by":"publisher","first-page":"234","DOI":"10.1016\/j.ejca.2018.11.007","article-title":"Performance of the Food and Drug Administration\/EMA-approved programmed cell death ligand-1 assays in urothelial carcinoma with emphasis on therapy stratification for first-line use of atezolizumab and pembrolizumab","volume":"106","author":"M Eckstein","year":"2019","journal-title":"Eur J Cancer"},{"key":"ref16","doi-asserted-by":"publisher","first-page":"480","DOI":"10.1159\/000527879","article-title":"Increasing Biomarker Guidance in the Treatment of Urothelial Carcinoma: Systematic Review of International Clinical Trials","volume":"107","author":"C Bolenz","year":"2023","journal-title":"Urol Int"},{"key":"ref17","doi-asserted-by":"publisher","first-page":"540","DOI":"10.1016\/j.cell.2017.09.007","article-title":"Comprehensive Molecular Characterization of Muscle-Invasive Bladder Cancer","volume":"171","author":"AG Robertson","year":"2017","journal-title":"Cell"},{"key":"ref18","doi-asserted-by":"publisher","first-page":"558","DOI":"10.1038\/nature13904","article-title":"MPDL3280A (anti-PD-L1) treatment leads to clinical activity in metastatic bladder cancer","volume":"515","author":"T Powles","year":"2014","journal-title":"Nature"},{"key":"ref19","doi-asserted-by":"publisher","first-page":"875","DOI":"10.1056\/NEJMoa2312117","article-title":"Enfortumab Vedotin and Pembrolizumab in Untreated Advanced Urothelial Cancer","volume":"390","author":"T Powles","year":"2024","journal-title":"N Engl J Med"},{"key":"ref20","doi-asserted-by":"publisher","first-page":"392","DOI":"10.1016\/j.annonc.2024.01.002","article-title":"TROPHY-U-01, a phase II open-label study of sacituzumab govitecan in patients with metastatic urothelial carcinoma progressing after platinum-based chemotherapy and checkpoint inhibitors: updated safety and efficacy outcomes","volume":"35","author":"Y Loriot","year":"2024","journal-title":"Ann Oncol"},{"key":"ref21","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1200\/JCO.23.02005","article-title":"Efficacy and Safety of Trastuzumab Deruxtecan in Patients With HER2-Expressing Solid Tumors: Primary Results From the DESTINY-PanTumor02 Phase II Trial","volume":"42","author":"F Meric-Bernstam","year":"2024","journal-title":"J Clin Oncol"},{"key":"ref22","doi-asserted-by":"publisher","first-page":"1041","DOI":"10.1200\/JCO.19.02044","article-title":"EV-101: A Phase I Study of Single-Agent Enfortumab Vedotin in Patients With Nectin-4-Positive Solid Tumors, Including Metastatic Urothelial Carcinoma","volume":"38","author":"J Rosenberg","year":"2020","journal-title":"J Clin Oncol"},{"key":"ref23","doi-asserted-by":"publisher","first-page":"1125","DOI":"10.1056\/NEJMoa2035807","article-title":"Enfortumab Vedotin in Previously Treated Advanced Urothelial Carcinoma","volume":"384","author":"T Powles","year":"2021","journal-title":"N Engl J Med"},{"key":"ref24","doi-asserted-by":"publisher","first-page":"863","DOI":"10.1111\/his.15130","article-title":"Associations of TACSTD2\/TROP2 and NECTIN-4\/NECTIN-4 with molecular subtypes, PD-L1 expression, and FGFR3 mutational status in two advanced urothelial bladder cancer cohorts","volume":"84","author":"V Bahlinger","year":"2024","journal-title":"Histopathology"},{"key":"ref25","doi-asserted-by":"publisher","first-page":"5123","DOI":"10.1158\/1078-0432.CCR-20-4175","article-title":"Heterogeneity in NECTIN4 Expression Across Molecular Subtypes of Urothelial Cancer Mediates Sensitivity to Enfortumab Vedotin","volume":"27","author":"CE Chu","year":"2021","journal-title":"Clin Cancer Res"},{"key":"ref26","doi-asserted-by":"publisher","first-page":"3003","DOI":"10.1158\/0008-5472.CAN-15-1313","article-title":"Enfortumab Vedotin Antibody-Drug Conjugate Targeting Nectin-4 Is a Highly Potent Therapeutic Agent in Multiple Preclinical Cancer Models","volume":"76","author":"PM Challita-Eid","year":"2016","journal-title":"Cancer Res"},{"key":"ref27","doi-asserted-by":"publisher","first-page":"1496","DOI":"10.1158\/1078-0432.CCR-22-1764","article-title":"Membranous NECTIN-4 Expression Frequently Decreases during Metastatic Spread of Urothelial Carcinoma and Is Associated with Enfortumab Vedotin Resistance","volume":"29","author":"N Klumper","year":"2023","journal-title":"Clin Cancer Res"},{"key":"ref28","doi-asserted-by":"publisher","first-page":"256","DOI":"10.1038\/s41585-024-00951-2","article-title":"Pre-treatment metastatic biopsy: a step towards precision oncology for urothelial cancer","volume":"22","author":"N Klumper","year":"2025","journal-title":"Nat Rev Urol"},{"key":"ref29","doi-asserted-by":"publisher","first-page":"224","DOI":"10.1016\/j.euf.2024.04.001","article-title":"Biomarkers of Response to Anti-NECTIN4 Antibody-Drug Conjugate Enfortumab Vedotin in Urothelial Cancer","volume":"10","author":"N Klumper","year":"2024","journal-title":"Eur Urol Focus"},{"key":"ref30","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1038\/nrc3817","article-title":"Molecular biology of bladder cancer: new insights into pathogenesis and clinical diversity","volume":"15","author":"MA Knowles","year":"2015","journal-title":"Nat Rev Cancer"},{"key":"ref31","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2022.111859","article-title":"Genomic heterogeneity as a barrier to precision oncology in urothelial cancer","volume":"41","author":"TN Clinton","year":"2022","journal-title":"Cell Rep"},{"key":"ref32","doi-asserted-by":"publisher","first-page":"406","DOI":"10.1038\/s41585-023-00725-2","article-title":"Circulating and urinary tumour DNA in urothelial carcinoma \u2013 upper tract, lower tract and metastatic disease","volume":"20","author":"KM Rose","year":"2023","journal-title":"Nat Rev Urol"},{"key":"ref33","doi-asserted-by":"publisher","first-page":"26","DOI":"10.1038\/s41585-024-00900-z","article-title":"Biological determinants of PSMA expression, regulation and heterogeneity in prostate cancer","volume":"22","author":"MK Bakht","year":"2025","journal-title":"Nat Rev Urol"},{"key":"ref34","doi-asserted-by":"publisher","first-page":"1091","DOI":"10.1056\/NEJMoa2107322","article-title":"Lutetium-177-PSMA-617 for Metastatic Castration-Resistant Prostate Cancer","volume":"385","author":"O Sartor","year":"2021","journal-title":"N Engl J Med"},{"key":"ref35","doi-asserted-by":"publisher","first-page":"27","DOI":"10.2967\/jnumed.115.162024","article-title":"Phase I Study of 68Ga-HER2-Nanobody for PET\/CT Assessment of HER2 Expression in Breast Carcinoma","volume":"57","author":"M Keyaerts","year":"2016","journal-title":"J Nucl Med"},{"key":"ref36","doi-asserted-by":"publisher","first-page":"3395","DOI":"10.1158\/1078-0432.CCR-23-0609","article-title":"First-in-Human Study of the Radioligand 68Ga-N188 Targeting Nectin-4 for PET\/CT Imaging of Advanced Urothelial Carcinoma","volume":"29","author":"X Duan","year":"2023","journal-title":"Clin Cancer Res"}],"container-title":["Aktuelle Urologie"],"original-title":[],"language":"de","link":[{"URL":"http:\/\/www.thieme-connect.de\/products\/ejournals\/pdf\/10.1055\/a-2622-6243.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,16]],"date-time":"2026-02-16T23:40:42Z","timestamp":1771285242000},"score":1,"resource":{"primary":{"URL":"http:\/\/www.thieme-connect.de\/DOI\/DOI?10.1055\/a-2622-6243"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7,1]]},"references-count":36,"journal-issue":{"issue":"01","published-online":{"date-parts":[[2026,2,16]]},"published-print":{"date-parts":[[2026,2]]}},"URL":"https:\/\/doi.org\/10.1055\/a-2622-6243","archive":["Portico","CLOCKSS"],"relation":{},"ISSN":["0001-7868","1438-8820"],"issn-type":[{"value":"0001-7868","type":"print"},{"value":"1438-8820","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,7,1]]}}}