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<p>For many decades, the treatment of metastatic urothelial carcinoma (mUC) was dominated by platinum-based chemotherapy. However, the introduction of immune checkpoint inhibitors in combination with modern antibody–drug conjugates (ADCs) and FGFR3 inhibitors has replaced this “old” standard due to significantly better efficacy. Although these therapies are targeted therapies, biomarker-driven therapy decisions are rarely used to date. The currently available biomarkers are also only helpful in isolated therapy situations. However, this could change fundamentally for ADCs in view of the pronounced expression variability of potential target structures such as NECTIN4, HER2, EGFR, and TROP2. The presence of activating FGFR3 mutations or fusions already defines a&#xa0;clearly delineated, albeit still small, therapeutic niche that could also gain importance in localized stages of urothelial carcinoma in the future. In order to be able to use these therapeutic innovations in a&#xa0;targeted and precise manner in the future, biomarker-based stratification of urothelial carcinomas is likely to play a&#xa0;greater role. Current developments thus open up considerable potential for true precision oncology.</p>

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Von ungezielt zu Präzisionsonkologie: Prädiktive Biomarker und Target-Therapien beim fortgeschrittenen Urothelkarzinom

  • 期刊论文

  • 发表日期：

    2026年1月28日

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  • Günter Niegisch,
  • Stefanie Zschäbitz,
  • Markus Eckstein,
  • Niklas Klümper

摘要

For many decades, the treatment of metastatic urothelial carcinoma (mUC) was dominated by platinum-based chemotherapy. However, the introduction of immune checkpoint inhibitors in combination with modern antibody–drug conjugates (ADCs) and FGFR3 inhibitors has replaced this “old” standard due to significantly better efficacy. Although these therapies are targeted therapies, biomarker-driven therapy decisions are rarely used to date. The currently available biomarkers are also only helpful in isolated therapy situations. However, this could change fundamentally for ADCs in view of the pronounced expression variability of potential target structures such as NECTIN4, HER2, EGFR, and TROP2. The presence of activating FGFR3 mutations or fusions already defines a clearly delineated, albeit still small, therapeutic niche that could also gain importance in localized stages of urothelial carcinoma in the future. In order to be able to use these therapeutic innovations in a targeted and precise manner in the future, biomarker-based stratification of urothelial carcinomas is likely to play a greater role. Current developments thus open up considerable potential for true precision oncology.