LHRH-Analoga zur Androgendeprivation beim Prostatakarzinom. Eine Evidenzlevelanalyse

Zusammenfassung

In diesem Übersichtsartikel sollen die Indikationen und der Einsatz der LHRH-Analoga in der heutigen Zeit dargestellt und erläutert werden. Hierzu erfolgte eine Literatursuche in Pubmed und der Cochrane-Datenbank. Ebenso wurden Leitlinien der EAU wie auch der AUA, sowie aktuelle Kongressbeiträge bis 2008 berücksichtigt. Seit 1991 erstmals in einer prospektiven Studie die Äquieffektivität der LHRH-Analogatherapie gegenüber der Orchiektomie beim metastasierten Prostatakarzinom bewiesen werden konnte, wurde der Einsatz der LHRH-Analoga zunehmend ausgebaut. Unter dieser Therapie erscheint eine Kontrolle der Testosteronspiegel nur sinnvoll, falls unter der LHRH-Analogatherapie ein PSA-Anstieg zu verzeichnen ist. Nach Absetzen der LHRH-Analogatherapie dauert es umso länger bis sich die Testosteronwerte erholen, je länger mit LHRH-Analoga therapiert worden ist. Hierbei ist zu beachten, das nach einer Therapiezeit von über 3 Jahren auf die mögliche Entwicklung einer Osteoporose oder eines Diabetes hingewiesen werden muss. Bei der neoadjuvanten und adjuvanten Androgendeprivation zeigt sich folgendes: vor einer radikalen Prostatektomie senkt eine Hormontherapie die Rate positiver Schnittränder und Lymphknotenmetastasen, aber eben nicht das tumorfreie Überleben. Vor einer Radiotherapie hingegen verbessert eine maximale Androgenblockade das PSA-freie Überleben. Die adjuvante Hormontherapie nach radikaler Prostatektomie verlängert das krankheitsfreie Überleben. Die ­adjuvante Hormontherapie nach Radiatio ver­längert das krankheitsfreie Überleben ebenso. Eine erhöhte kardiovaskuläre Toxizität wurde nicht bestätigt. Eine intermittierende Androgendeprivation erscheint genauso wirksam wie eine kontinuierliche Behandlung unter Reduktion der Nebenwirkungen. Eine Salvage-Hormontherapie ist bei einer kurzen PSA-Verdopplungszeit oder PSA-Anstiegsgeschwindigkeit von > 2 ng / ml / Jahr indiziert. Der Wert eines frühen Beginns (PSA ≤ 10 ng / ml, PSA Verdopplungszeit ≤ 12 Monate) kann das metastasenfreie Überleben hierbei verlängern.

Abstract

In this review the current indications and the options for LHRH analogues are elucidated. For this purpose, a literature search in PubMed and the Cochrane-Database was performed. In addition, the EAU and AUA guidelines as well as actual meeting abstracts up to 2008 were taken into account. Since the first prospective study in 1991 showed the same effectivity for LHRH analogues and orchiectomy in metastasised prostate cancer patients, the use of LHRH analogues increased thereafter. Testosterone levels do not need to be checked regularly, but rather only when PSA rises again under treatment. After cessation of LHRH analogue treatment the time to testosterone level recovery is longer when the treatment time was longer. One must especially recognise the risks of diabetes and osteoporosis after more than 3 years of LHRH analogue treatment. In the case of neoadjuvant and adjuvant LHRH analogue treatment, several points have to be taken into consideration: LHRH analogues before radical prostatectomy lead to a lower positive margin rate and lower rate of lymph node metastasis, but tumour-specific survival is not improved. In contrast, neoadjuvant LHRH analogue treatment before radiation therapy leads to better tumour-specific and overall survival. An increased cardiovascular toxicity was not observed. Intermittent androgen ablation has been proved to be equivalent with a reduction of side effects. Hormonal salvage therapy should be initiated when the PSA doubling time is short or the PSA velocitiy is > 2 ng / mL / year. The benefit of early initiation (PSA < 10 ng / mL, PSA doubling time < 12 months) is that it can prolong the metastasis-free survival time.

Schlüsselwörter

Prostatakarzinom - LHRH-Analoga - PSA - Hormontherapie - Metastasen

Key words

prostate cancer - LHRH analogues - PSA - hormonal therapy - metastasis

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