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Androgendeprivation in der Therapie des Prostatakarzinoms

Androgen deprivation for advanced prostate cancer

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Zusammenfassung

Die Androgendeprivation (ADT) durch medikamentöse oder chirurgische Kastration stellt die Therapie der Wahl des systemisch oder lokoregionär metastasierten Prostatakarzinoms (PCA) dar. Obwohl die ADT seit über 60 Jahren erfolgreich etabliert ist, bestehen wesentliche Kontroversen über Verfahren (medikamentös oder chirurgisch), Beginn (sofort oder verzögert), Art (komplette oder einfache Blockade) und Dauer der ADT (kontinuierlich oder intermittierend). In der vorliegenden Übersicht sollen die verschiedenen Optionen der ADT kritisch bewertet werden.

Die bilaterale subkapsuläre Orchiektomie und die Applikation von LHRH-Analoga repräsentieren die Standardtherapie, während die Behandlung mit Östrogenen aufgrund der kardiovaskulären Komplikationen trotz vergleichbarer therapeutischer Effektivität nicht empfohlen wird. Die antiandrogene Monotherapie mit Bicalutamid weist bei minimaler Metastasenlast der LHRH-Therapie vergleichbare Überlebensraten auf, während bei ausgedehnter Metastasenlast die LHRH-Gabe favorisiert werden sollte. Die maximale ADT erbringt nur einen marginalen Überlebensbenefit von 5% für Patienten mit geringer Metastasenlast und bedarf einer kritischen Indikationsstellung.

Die frühe ADT erbringt beim metastasierten PCA einen Vorteil in Bezug auf das symptomfreie Überleben und sollte zur Vermeidung signifikanter Komplikationen frühzeitig eingeleitet werden – die frühe ADT übt jedoch keinen Vorteil auf das progressionsfreie und das Gesamtüberleben aus. Die intermittierende ADT stellt trotz erster viel versprechender Resultate aufgrund fehlender Daten prospektiv randomisierter Studien weiterhin eine experimentelle Therapie mit dem Vorteil einer verbesserten Lebensqualität für ausgewählte Patienten dar. Während die adjuvante ADT bei lymphonodulär metastasiertem PCA nach radikaler Prostatektomie weiterhin kontrovers diskutiert wird, ist der adjuvante Einsatz nach perkutaner Radiatio wegen eines lokal fortgeschrittenen PCA über mindestens 2 Jahre mit einem signifikanten Benefit bezüglich des progressionsfreien und des Gesamtüberlebens verbunden und stellt den aktuellen Standard der Therapie dar.

Abstract

Androgen deprivation (ADT) by medical or surgical castration represents the standard therapeutic approach for managing prostate cancer (PCA) with systemic or locoregional metastases. Although ADT has been successfully used for more than 60 years, there are still major controversies with regard to the initiation (early versus delayed), type (complete versus monotherapy), and duration (continuous versus intermittent) of treatment. It is the purpose of this review to critically present the results of the various ADT options.

Bilateral orchiectomy and subcutaneous application of luteinising hormone-releasing hormone (LHRH) analogues represent the guideline-recommended standard treatment for metastatic PCA, whereas estrogens are no longer recommended because of significant cardiovascular side effects despite comparable therapeutic efficacy. Antiandrogen monotherapy with bicalutamide is comparable to LHRH analogues in men with minimal tumour burden. However, survival rates are inferior in patients with extensive metastatic disease, in whom medical or surgical castration should be favoured. Complete ADT results in a median survival benefit of about 5% in men with low metastatic tumour burden, and it cannot be recommended for routine use.

Early ADT is associated with a significant advantage in terms of symptom-free survival and prevention of metastasis-associated complications, but it does not result in a prolonged progression-free and overall survival when compared with delayed ADT. Despite encouraging results, intermittent ADT remains an experimental therapeutic approach that should be considered on an individual basis in carefully selected patients. Adjuvant ADT is still discussed controversially for men after radical prostatectomy, whereas it has become the standard approach in patients who undergo external beam radiation for locally advanced PCA.

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  1. Bereich Urologische Onkologie,Klinik und Poliklinik für Urologie, Universität zu Köln, Joseph-Stelzmann-Straße 9, 50924, Köln, Deutschland

    A. Heidenreich, D. Pfister, C.H. Ohlmann & U.H. Engelmann

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Heidenreich, A., Pfister, D., Ohlmann, C. et al. Androgendeprivation in der Therapie des Prostatakarzinoms. Urologe 47, 270–283 (2008). https://doi.org/10.1007/s00120-008-1636-2

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