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Aktuelle Urol 2019; 50(05): 513-523
DOI: 10.1055/a-0895-9201
Übersicht
© Georg Thieme Verlag KG Stuttgart · New York

Personalisierte Medizin bei Nierenzelltumoren

Personalised medicine in renal cell tumours
Kerstin Junker
Saarland University, Dept of Urology and Pediatric Urology, Homburg
,
Philip Zeuschner
Saarland University, Dept of Urology and Pediatric Urology, Homburg
› Author Affiliations
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Publication History

Publication Date:
05 June 2019 (online)

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Zusammenfassung

Die Entdeckung von immer kleineren Tumoren durch den umfassenden Einsatz von bildgebenden Verfahren, die Erweiterung der operativen Techniken und der systemischen Therapieoptionen fordern auch für Nierentumorpatienten eine Individualisierung der Therapie. Essenzielle Voraussetzung ist dabei die Kenntnis der Tumorbiologie, da sie eine differenzierte Diagnostik, individuelle Prognosebewertung und Therapiewahl, basierend auf Biomarkern, und die Entwicklung von neuen Therapiestrategien ermöglicht.

Nierenzelltumore werden aktuell in 16 histologische Subtypen unterschieden, die durch spezifische genetische Veränderungen charakterisiert sind. Aufgrund ihrer unterschiedlichen Aggressivität ist die Kenntnis der Subtypen sowohl für die Therapieentscheidung als auch für die Nachsorge wichtig. Molekulare Marker können bei der Differenzialdiagnose eingesetzt werden. Molekulare Signaturen werden zukünftig aber auch wesentlich zur Prognosedifferenzierung innerhalb der Subtypen beitragen, wie für das klarzellige Nierenzellkarzinom bereits gezeigt wurde. Dies wird zur Entwicklung differenzierter Nachsorgeprotokolle und zu einer genaueren Selektion der Patienten für adjuvante Therapien führen. Für metastasierte Patienten stehen immer mehr medikamentöse Therapien zur Verfügung, die zielgerichtet in bestimmte zelluläre Signal- oder Kommunikationswege eingreifen. Auch wenn bisher noch keine validen prädiktiven Biomarker verfügbar sind, liegen vielversprechende Daten zu molekularen Signaturen in Korrelation mit dem Ansprechen auf Tyrosinkinaseinhibitoren oder Checkpointinhibitoren vor, die in Zukunft wesentlich besser als die klinischen Scores eine individuelle Therapiewahl ermöglichen werden.

Zur Überführung der vielversprechenden Biomarker in die klinische Praxis sind nun prospektive multizentrische Studien erforderlich. Die Berücksichtigung von bereits vorhandenen Erkenntnissen aus der Tumorbiologie der verschiedenen NZK-Entitäten sowohl bez. der veränderten Signalwege in den Tumorzellen selbst als auch der Rolle des Mikromilieus einschließlich der Immunzellen ist eine essenzielle Voraussetzung für eine weitere Verbesserung von Diagnostik und Therapie.

Abstract

The extensive use of abdominal imaging reveals an increasing number of small and asymptomatic kidney tumours, for which primary treatment versus observation strategies need to be discussed. Elaborate surgical techniques and a variety of systemic treatment options are available for patients with localised and advanced tumours. This necessitates a demanding and complex individualised decision-making process. A better understanding of tumour biology including validated biomarkers is therefore essential in order to improve diagnostics, prognostic evaluation and therapeutic strategies.

Renal cell tumours are currently subdivided into 16 histological subtypes, each characterised by specific genetic changes. As tumour aggressiveness differs significantly, knowledge of these distinct subtypes is important for adequate treatment choice and follow-up. Molecular markers may facilitate an exact diagnosis and will further differentiate the individual prognosis within each subtype, which is already possible for clear cell renal cell carcinoma (RCC). This will lead to individualised follow-up protocols and a better selection of patients benefitting from observational or adjuvant strategies after surgery.

For metastatic tumours, the number of systemic treatment options targeting specific cellular signal or communication pathways has increased tremendously. Valid predictive biomarkers for differential treatment are not available to date. However, there is promising evidence of correlations between molecular signatures and treatment response to tyrosine kinase inhibitors or checkpoint inhibitors. Biomarkers will most likely supersede clinical scores for individual treatment selection in the near future.

Prospective multicentre studies are needed so that promising biomarkers can be implemented in daily clinical practice in due consideration of existing insights from the tumour biology of the distinct RCC subtypes. This is essential for further improvement of diagnosis and treatment.

Schlüsselwörter

Nierenzelltumore - Nierenzellkarzinome - Biomarker - Prognose - Diagnose

Keywords

renal cell carcinoma - biomarker - prognosis - renal cell tumour - diagnosis
 

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