Hormontherapie des Prostatakarzinoms - Übersicht und aktueller Stand

Zusammenfassung

Das Prostatakarzinom (PC) ist in der westlichen Welt der häufigste bösartige Tumor des Mannes. Durch die Einführung des PSA-Screenings wird das es zunehmend in potenziell kurablen Tumorstadien diagnostiziert. Dennoch kommt es nach kurativer Therapie innerhalb von 15 Jahren in bis zu 50 % zu einem erneuten Anstieg des PSA-Wertes und im Median nach weiteren 8 Jahren in 34 % zu einer Metastasenbildung. Beim systemischen Rezidiv ist die Hormontherapie die wichtigste palliative Maßnahme. Sie wird ebenfalls als Primärtherapie und in Kombination mit anderen Therapieformen eingesetzt. Die verschiedenen Methoden der Kastration (chirurgisch, medikamentös) sind vom Gesamtüberleben her vergleichbar. Die heutzutage für die medikamentöse Kastration eingesetzten LH-RH-Agonisten haben typische Nebenwirkungen in Form von Impotenz (69 %), Hitzewallungen (56,5 %), Gynäkomastie (24,9 %) und Osteoporose. Initial führen LH RH-Agonisten zu einem passageren Serum-Testosteronanstieg (Flare-Phänomen). Dies kann durch LH-RH-Antagonisten vermieden werden, die in Europa noch nicht zugelassen ist. Eine weitere Medikamentengruppe sind die Antiandrogene, die ein günstigeres Nebenwirkungsprofil als die Formen der Kastration besitzen. Das Antiandrogen Bicalutamid führt beim lokal fortgeschrittenen PC, adjuvant zur Radiatio verabreicht, zu einer Überlebensverlängerung, nicht aber bei der Gabe nach radikaler Prostatektomie oder bei Versagen einer „Watchful-waiting”-Strategie. Beim metastasierten PC sind Antiandrogene der Kastration im Gesamtüberleben statistisch signifikant unterlegen. Die Bedeutung der maximalen Androgenblockade (Kombination aus Kastration und Antiandrogen) wird anhaltend kontrovers diskutiert. Sie bietet beim metastasierten PC einen geringen Überlebensvorteil von wenigen Monaten bei deutlicher Zunahme der Nebenwirkungen.

Summary

Prostatic cancer (PC) heads the list of malignant tumors in the male. Resulting from the introduction of prostatic-specific antigen (PSA) screening there has been a shift towards potentially curable tumor stages. However, after curative treatment a rise in PSA has been noted in up to 50% of cases within 15 years. Metastases are then reported in up to 34% within the subsequent eight years. Hormonal therapy represents the most important palliative measure in metastatic PC and is also used in primary, adjuvant and neo-adjuvant hormonal treatment. The different methods of castration (orchidectomy, medical castration) are equivalent in respect of overall survival. The side effects of agonists of luteinizing-hormone-releasing hormone (LHRH) are impotence (69%), hot flushes (56.5%), gynecomastia (24.9%) and osteoporosis and may initially cause a transitory increase in serum testosterone (flare phenomenon). This can be counteracted by an LHRH antagonist (not available in Europe). Anti-androgens do not lead to testosterone suppression and have a more favorable profile of side effects. Bicalutamide significantly improves overall survival rate in patients receiving radiotherapy. However, overall survival rate is not improved in patients after radical prostatectomy or under watchful waiting. Bicalutamide alone is less efficacious than castration in patients with metastases. The use of maximal androgen blockade (combination of castration and anti-androgen) remains controversial. It seems to produce a modest overall and cancer-specific increase in survival rate but is associated with increased adverse events and a reduced quality of life.

Schlüsselwörter

Prostatakarzinom - Hormontherapie - Kastration - maximale Androgenblockade - Flare - Phänomen

Key words

prostate cancer - hormone therapy - castration - maximal androgen blockade - flare phenomenon

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