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Systemtherapie des metastasierten Tumors des oberen Harntraktes

Systemic treatment of metastatic tumors of the upper urinary tract

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Zusammenfassung

Hintergrund

Mehr als 95 % der Tumoren des oberen Harntraktes (OHT) sind korrespondierend zum Harnblasenkarzinom Urothelkarzinome. Bei Erstdiagnose liegt in ca. 60 % ein invasives Wachstum vor. Im Falle von Fernmetastasen (M+) zeigt sich kein Benefit einer radikalen Nephroureterektomie. Hier besteht die Indikation zur Systemtherapie.

Fragestellung

Ziel dieser Arbeit ist die systematische Aufarbeitung der vorliegenden Literatur und Darlegung der verschiedenen Systemtherapien beim lokal fortgeschrittenen oder metastasierten Urothelkarzinom des OHT („upper tract urothelial carcinoma“, UTUC).

Ergebnisse

Insgesamt ist die Datenlage für die Systemtherapie beim lokal fortgeschrittenen oder metastasierten UTUC eingeschränkt. Analog zum Harnblasenkarzinom haben sich Cisplatin-basierte Chemotherapieprotokolle in der Erstlinientherapie etabliert. Der Kombination mit Gemcitabin und Cisplatin (GC) wird hierbei der Vorzug gegeben. Dies ist maßgeblich auf die geringere Toxizität im Vergleich zum MVAC-Protokoll (Methotrexat, Vinblastin, Adriamycin und Cisplatin) zurückzuführen. Carboplatin-basierte Chemotherapien haben sich hingegen nicht bewährt. Immunmodulative Therapien durch Checkpoint-Inhibitoren gegen PD-1 („programmed cell death 1“), PD-L1 („programmed cell death ligand 1“) oder CTLA-4 („cytotoxic T‑lymphocyte antigen-4“) haben signifikante antitumorale Aktivität mit tolerablen Nebenwirkungen und dauerhaftem Ansprechen bei Patienten mit lokal fortgeschrittenem und metastasiertem Urothelkarzinom gezeigt. Patienten mit fortgeschrittenem oder metastasiertem Urothelkarzinom, bei denen Cisplatin kontraindiziert war, zeigten bei positivem PD-L1-Status gute Ansprechraten. Vorläufige Daten aus der derzeit laufenden KEYNOTE-361 und IMvigor130 zeigen in der Erstlinientherapie im Vergleich zur Standardchemotherapie eher ein verringertes Überleben bei schwacher PD-L1-Expression.

Abstract

Background

Similar to bladder cancer, more than 95% tumors of the upper urinary tract are urothelial carcinoma. At initial diagnosis approximately 60% of the tumors are already invasive. In case of distant metastasis (M+) there is no benefit of radical nephroureterectomy. In those cases, systemic therapy is indicated.

Objectives

The aim of this article is to present a systematic overview of different therapies in patients with metastatic upper tract urothelial carcinoma (UTUC).

Results

Currently there are insufficient data upon which the recommendations for treatment of locally advanced and metastatic UTUC can be based. Cisplatin-based chemotherapy is the gold standard in first-line treatment of metastatic UTUC. Due to a lower toxicity compared to MVAC (methotrexate, vinblastine, adriamycin plus cisplatin), gemcitabine and cisplatin have become standard. However, carboplatin-based chemotherapies should not be considered interchangeable. Immunomodulatory therapies using checkpoint inhibition, particularly with antibodies directed against PD-1 (programmed cell death 1), PD-L1 (programmed cell death ligand 1) or CTLA-4 (cytotoxic T‑lymphocyte antigen-4) have shown significant antitumor activity with tolerable safety profiles and durable responses in patients with locally advanced and metastatic urothelial carcinoma. In those patients, unfit for cisplatin-based chemotherapy, good response rates have been reported in case of a positive PD-L1 status. However, preliminary data of the KEYNOTE-361 and IMvigor130 studies showed a reduced survival in case of low PD-L1 expression.

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Authors and Affiliations

  1. Klinik und Poliklinik für Urologie, Kinderurologie und Uroonkologie, Universitätsmedizin Essen, Hufelandstr. 55, 45147, Essen, Deutschland

    C. Darr, B. A. Hadaschik &  S. Tschirdewahn

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  1. C. Darr
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  2. B. A. Hadaschik
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  3. S. Tschirdewahn
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Correspondence to S. Tschirdewahn.

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C. Darr, B. A. Hadaschik und S. Tschirdewahn geben an, dass kein Interessenkonflikt besteht.

Dieser Beitrag beinhaltet keine von den Autoren durchgeführten Studien an Menschen oder Tieren.

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Darr, C., Hadaschik, B.A. & Tschirdewahn, S. Systemtherapie des metastasierten Tumors des oberen Harntraktes. Urologe 58, 30–33 (2019). https://doi.org/10.1007/s00120-018-0835-8

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