Ziel: 20 statt 50! Aktuelle Daten zum Zielwert der Testosteronsenkung und die Forschung hierüber seit erster „LH-RH“ (GnRH)-Analoga-Gabe an Patienten vor 40 Jahren

Zusammenfassung

Beim ersten Einsatz eines LH-RH (heute: GnRH)-Analogon zur Therapie des Prostatakarzinoms war das Kastrationsniveau von unter 50 ng/dl willkürlich festgelegt. Seither zeigen zahlreiche Untersuchungen, dass mit einer dauerhaften Senkung des Testosteronspiegels, wie z. B. durch Buserelin, auf Werte von unter 20 ng/dl eine deutliche Verbesserung des Outcome einhergeht. Dies wird in aktuellen Studien belegt, sodass der Kastrationsspiegel mit Werten von unter 20 ng/dl zu fordern ist. Darüber hinaus stellt der Hormonentzug mit GnRH-Analoga weiterhin die Basistherapie für neue Therapieoptionen wie z. B. mit Abirateron, Enzalutamid bzw. Apalutamid dar.

Abstract

When LH-RH (now: GNRH) analogues were first used for the treatment of prostate cancer, the castration level was arbitrarily defined as a testosterone level of less than 50 ng/dl. Since then, numerous studies have shown that a permanent lowering of the testosterone level, e. g. by buserelin, to values lower than 20 ng/dl is associated with a significant improvement in outcomes. This has been proven in recent studies. Therefore, a castration level with testosterone values of less than 20 ng/dl is required. In addition, hormone withdrawal with GNRH analogues continues to provide the basic therapy for new treatment options, e. g. with abiraterone, enzalutamide or apalutamide.

Schlüsselwörter

Kastrationsniveau - Testosteronsenkung - Buserelin - LHRH - ADT

Keywords

testosterone reduction - buserelin - LHRH - ADT - castration level

Publication History

Article published online:
18 March 2020

• Literatur

• 1 Pettersson B, Varenhorst E, Petas A. et al. Duration of Testosterone Suppression after a 9. 45 mg Implant of the GnRH-Analogue Buserelin in Patients with Localised Carcinoma of the Prostate. A 12-Month Follow-up Study. European Urology 2006; 50: 483-489
• 2 Morote J, Planas J, Salvador C. et al. Individual variations of serum testosterone in patients with prostate cancer receiving androgen deprivation therapy. BJUI 2008; 50: 332-335
• 3 Klotz L, OʼCallaghan C, Ding K. et al. Nadir Testosterone Within First Year of Androgen - Deprivation Therapy (ADT) Predicts for Time to Castration-Resistant Progression: A Secondary Analysis of the PR-7 Trial of Intermittent Versus Continuous ADT. Journal of Clinical Oncology 2015; 33: 1151-1156
• 4 Ding M, Lee T, Di Lena R. et al. Investigating the Impact of a Lower Testosterone Threshold on Castration-Resistant Progression in Patients on Continuous Androgen Deprivation Therapy. AUA, Chicago (MP22-04). 2019
• 5 Hupe MC, Hammerer P, Ketz M. et al. Retrospective Analysis of Patients With Prostate Cancer Initiating GnRH Agonists/Antagonists Therapy Using a German Claims Database: Epidemiological and Patient Outcomes. Front Oncol 2018; 8: 543
• 6 Merseburger AS, Hammerer P, Rozet F. et al. Androgen deprivation therapy in castrate-resistant prostate cancer: how important is GnRH agonist backbone therapy?. World J Urol 2015; 33: 1079-1085
• 7 Merseburger AS, Alcaraz A, von Klot CA. Androgen deprivation therapy as backbone therapy in the management of prostate cancer. Onco Targets Ther 2016; 9: 7263-7274
• 8 Gleave M. Management of metastatic castration-sensitive/naive prostate cancer. Basel APCCC. 2019
• 9 European Medicines Agency. Review of handling errors with depot formulations of leuprorelin medicines started. EMA/316598/2019.
• 10 Breul J, Lundström E, Purcea D. et al. Efficacy of Testosterone Suppression with Sustained-Release Triptorelin in Advanced Prostate Cancer. Adv Ther 2017; 34: 513-523
• 11 Solarić M, Bjartell A, Thyroff-Friesinger U. et al. Testosterone suppression with a unique form of leuprorelin acetate as a solid biodegradable implant in patients with advanced prostate cancer: results from four trials and comparison with the traditional leuprorelin acetate microspheres formulation. Ther Adv Urol 2017; 9: 127-136
• 12 Shore ND, Chu F, Moul J. et al. Polymer-delivered subcutaneous leuprolide acetate formulations achieve and maintain castrate concentrations of testosterone in four open-label studies in patients with advanced prostate cancer. BJU Int 2017; 119: 239-244
• 13 Meani D, Solarić M, Visapää H. et al. Practical differences between luteinizing hormone-releasing hormone agonists in prostate cancer: perspectives across the spectrum of care. Ther Adv Urol 2017; 10: 51-63
• 14 Bolton EM, Lynch T. Are all gonadotrophin-releasing hormone agonists equivalent for the treatment of prostate cancer? A systematic review. BJU Int 2018; 122: 371-383
• 15 Hussain M, Fizazi K, Saad F. et al. Enzalutamide in Men with Nonmetastatic, Castration-Resistant Prostate Cancer. N Engl J Med 2018; 378: 2465-2474
• 16 Smith MR, Saad F, Chowdhury S. et al. Apalutamide Treatment and Metastasis-free Survival in Prostate Cancer. N Engl J Med 2018; 378: 1408-1418
• 17 Chi KN, Agarwal N, Bjartell A. et al. Apalutamide for Metastatic, Castration-Sensitive Prostate Cancer. N Engl J Med 2019; 381: 13-24
• 18 von Klot CA, Kuczyk MA, Boeker A. et al. Role of free testosterone levels in patients with metastatic castration-resistant prostate cancer receiving second-line therapy. Oncol Lett 2017; 13: 22-28