Gegenwärtige und zukünftige Therapiestratifizierung des metastasierten Urothelkarzinoms: eine große Chance für eine echte Präzisionsonkologie

 

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Zusammenfassung

Die Therapie des metastasierten Urothelkarzinoms (mUC) wurde viele Jahrzehnte durch platinhaltige Chemotherapien dominiert. Spätestens mit der Einführung von Immuncheckpoint-Inhibitoren, insbesondere in Kombination mit modernen Antikörper-Wirkstoff-Konjugaten (ADC) und FGFR3-Inhibitoren, wurde dieser Therapiestandard in einigen Indikationen überholt. Dennoch kommen biomarkergesteuerte Therapieentscheidungen bislang selten zum Einsatz. Die bislang verfügbaren Biomarker helfen allerdings bislang auch nur in vereinzelten Therapiesituationen. Für ADCs könnte sich dies allerdings bei einer hohen Expressionsvariabilität verschiedener Targets wie NECTIN-4, Her2neu, EGFR und TROP2 substanziell verändern. Das Vorhandensein von aktivierenden FGFR3-Mutationen oder -Fusionen eröffnet zudem eine klar definierte, wenn auch kleine therapeutische Nische, die unter Umständen in Zukunft für lokalisierte Stadien des Urothelkarzinoms größer werden könnte. Um diese therapeutischen Neuerungen in Zukunft zielgerecht und präzise steuern und einsetzen zu können, wird eine Biomarkerstratifizierung von Tumoren in Zukunft vermutlich abdingbar werden. Die aktuellen Entwicklungen stellen somit ein großes Potenzial für eine echte Präzisionsonkologie dar.

Abstract

For many decades, the treatment of metastatic urothelial carcinoma (mUC) has been dominated by platinum-containing chemotherapies. The latest version is the introduction of immune checkpoint inhibitors, especially in combination with modern antibody-drug conjugates (ADC) and FGFR3 inhibitors, but this therapeutic standard has been overtaken in some indications. Nevertheless, biomarker-guided therapy decisions have rarely been used to date. However, the biomarkers available to date have only helped in isolated therapeutic situations. For ADCs, however, this could change substantially when there is high expression variability of various targets such as NECTIN-4, Her2neu, EGFR and TROP2. The presence of activating FGFR3 mutations or fusions also opens up a clearly defined, albeit small, therapeutic niche that could possibly become larger in the future for localised stages of urothelial carcinoma. Biomarker stratification of tumours will presumably become indispensable in the future if we are to control and use these therapeutic innovations in a targeted and precise manner. Current developments therefore possess great potential for genuine precision oncology.

Publication History

Received: 02 May 2025

Accepted after revision: 22 May 2025

Article published online:
01 July 2025

© 2025. Thieme. All rights reserved.

Georg Thieme Verlag KG
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