Aktuelle Urol 2019; 50(04): 378-385
DOI: 10.1055/a-0966-8380
Übersicht
© Georg Thieme Verlag KG Stuttgart · New York

50 Jahre Nierenzellkarzinom

50 years of renal cell carcinoma
Christian Doehn
Urologikum Lübeck, Urologikum Lübeck, Lübeck
› Institutsangaben
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Publikationsverlauf

Publikationsdatum:
09. August 2019 (online)

Zusammenfassung

In den letzten 50 Jahren konnten auch beim Nierenzellkarzinom viele Wissenlücken geschlossen werden. Die Pathologie hat zu einer einheitlichen Klasifikation gefunden und verschiedene histologische Subtypen detektiert. Beim klarzelligen Nierenzellkarzinom kommt dem (mutierten) von-Hippel-Lindau-Gen auf dem Chromosom 3 eine überragende Bedeutung zu.

Die operative Therapie des nichtmetastasierten Nierenzellkarzinoms hat über die radikale Nephrektomie zu einer dem Tumorstadium angemessenen Operation mit Belassen der Nebeniere und Etablierung der nierenerhaltenden Operationstechniken gefunden. Dies geschieht heute zunehmend laparoskopisch bzw. roboterassitiert. Noch minimal-inasiver ist dann nur die Kryoablation, Radiofrequenzablation oder die aktive Überwachung – jeweils für den kleinen Nierentumor bis 4 cm und strenger Indikationsstellung.

Beim metastasierten Nierenzellkarzinom dominiert die systemische Therapie. Schnell war erkannt, dass Chemotherapeutika nicht zur Therapie des Nierenzellkarzinoms geeignet sind. Die Ära der Zytokintherapie – immerhin über 20 Jahre eingesetzt – ist unvergessen. Die fortgeschriebenen Erkenntnisse zur Mutation des von-Hippel-Lindau-Gens mit Akkumulation des hypoxieinduzierenden Faktors und nachfolgend erhöhter Transkription von vaskulärem endothelialem Wachstumsfaktor (VEGF) waren Rationale für den erfolgreichen Einsatz von Tyrosinkinase-Inhibitoren, mTOR-Inhibitor und VEGF-Antikörpern wie wir sie seit 2006 kennen. Der Einsatz der Checkpoint-Inhibitoren hat die systemische Therapie des Nierenzellkarzinoms erneut und relevant verändert.

Abstract

In the past 50 years, many knowledge gaps regarding renal cell carcinoma (RCC) have been closed. A pathological tumour classification has been developed and different histological subtypes are known today. In clear cell RCC, the (mutated) von Hippel-Lindau gene located on chromosome 3 is highly important.

Operative therapy of non-metastatic RCC has evolved from radical nephrectomy to less radical techniques including procedures sparing the adrenal gland as well as nephron-sparing surgery. Surgical procedures are increasingly performed using laparoscopic or robot-assisted approaches. Even less invasive techniques such as cryoablation, radiofrequency ablation or active surveillance are applied for small renal masses, if indicated.

Metastatic RCC is most commonly treated by systemic therapy. Chemotherapy has no effect in RCC. For more than 20 years, cytokine therapy was the standard of care for metastatic RCC. Mutations of the von Hippel-Lindau gene associated with accumulation of hypoxia-inducible factor, followed by increased transcription of vascular endothelial growth factor, provided the scientific rationale for the successful use of tyrosine kinase inhibitors, mTOR inhibitors, and anti-VEGF antibodies introduced in 2006. The development of checkpoint inhibitors has changed the systemic treatment of RCC in yet another relevant manner.

 
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