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Molekulare Subtypen des Urothelkarzinoms der Harnblase – Hintergründe und klinische Relevanz

Molecular subtypes of urothelial carcinoma of the bladder—background and clinical relevance

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Zusammenfassung

Das Urothelkarzinom der Harnblase hat im fortgeschrittenen und metastasierten Stadium oft eine eingeschränkte Prognose. Chemotherapie und Immuntherapie bilden derzeit die Standardbehandlungsoptionen im systemischen Erkrankungsmanagement. Mit dem Ziel der Präzisionsmedizin und Prognoseverbesserung wurden in den vergangenen Jahren durch mehrere Gruppen intrinsische molekularen Subtypen des Urothelkarzinoms der Harnblase definiert. Die vorliegende Arbeit gibt einen Überblick über die Hintergründe und die klinische Relevanz dieser molekularen Subtypen des Urothelkarzinoms der Harnblase und bildet den aktuellen Standard sowie jüngste Entwicklungen ab. Dabei wurden die relevante Literatur und aktuelle Studiendaten ausgewertet, eine Kongruenz der verschiedenen publizierten Klassifikationsansätze diskutiert und die möglichen therapeutischen Implikationen der molekularen Subtypen zusammengestellt. Obwohl große und vielversprechende Fortschritte auf dem Gebiet der molekularen Charakterisierung des Urothelkarzinom der Harnblase in den vergangenen Jahren erreicht wurden, scheint die „prime time“ für den klinischen Einsatz der bislang definierten Subtypen noch nicht gekommen. Hierzu fehlen bis dato immer noch prospektive und multizentrische Studien mit einheitlichen molekularen Definitionen, sowie Standardisierungen bei der Probenaufarbeitung, einfache Analyseprotokolle mit reduzierten Genpanels und die Entwicklung einer Leitlinie für zielgerichtete Therapieregime. Grundsätzlich ist die Generalisierbarkeit der Methodik gefragt, um personalisierte Therapiekonzepte nicht nur an wenigen ausgewählten Expertenzentren, sondern auch in der breiteren Anwendung durchführen zu können.

Abstract

Advanced and metastatic stages of bladder cancer are associated with a poor prognosis. Therapy options are currently limited to systemic therapy with chemo- and immunotherapeutics. In order to improve individual therapy and especially to achieve a more favorable prognosis for these patients, intrinsic molecular subtypes have recently been identified in urothelial carcinoma of the bladder. This review article presents the latest developments, background, and clinical relevance of molecular subtypes in urothelial carcinoma of the bladder. The existing literature and current study data were analyzed to present and evaluate the different molecular classification systems. A focus was placed on the possible therapeutic implications of these molecular subtypes. Although promising progress has been made in the molecular subtyping of urothelial carcinoma, this classification has not yet found its way into clinical application. Multicenter prospective studies with standardized study protocols are still lacking. Previous studies differ in molecular markers, sample collection and preparation procedures, and analytical protocols. Standardization is urgently needed before guidelines can be established and targeted treatment regimens implemented. In principle, the aim should be to develop a stable and as simple as possible methodology, enabling personalized treatment based on molecular subtypes to be broadly applied, and not just in specialized expert centers.

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Authors and Affiliations

  1. Klinik für Urologie und Urochirurgie, Medizinische Fakultät Mannheim, Universität Heidelberg, Mannheim, Deutschland

    Philipp Erben

  2. Fachgruppe Molekulare Urologie der Arbeitsgruppe urologische Forschung (AuF) der Deutschen Gesellschaft für Urologie, Berlin, Deutschland

    Philipp Erben,  Christoph Becker, Igor Tsaur, Matthias B. Stope & Tilman Todenhöfer

  3. Forschungskoordination, Deutsche Gesellschaft für Urologie (DGU) e. V., Uerdinger Straße 64, 40474, Düsseldorf, Deutschland

    Christoph Becker

  4. Klinik für Urologie und Kinderurologie, Universitätsmedizin Mainz, Mainz, Deutschland

    Igor Tsaur

  5. Klinik für Gynäkologie und Gynäkologische Onkologie, Universitätsklinikum Bonn, Bonn, Deutschland

    Matthias B. Stope

  6. Studienpraxis Urologie, Nürtingen, Deutschland

    Tilman Todenhöfer

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P. Erben, C. Becker, I. Tsaur, M.B. Stope und T. Todenhöfer geben an, dass kein Interessenkonflikt besteht.

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Erben, P., Becker, C., Tsaur, I. et al. Molekulare Subtypen des Urothelkarzinoms der Harnblase – Hintergründe und klinische Relevanz. Urologe 60, 81–88 (2021). https://doi.org/10.1007/s00120-020-01396-2

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