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Aktuelle Urol
DOI: 10.1055/a-2055-0869
Übersicht

Management des metastasierten hormonsensitiven Prostatakarzinoms

Aktuelle Therapieoptionen, Kriterien für Progression und TherapiewechselManagement of metastatic hormone-sensitive prostate cancerCurrent treatment options, criteria for progression and switch of therapy
Kurt Miller
1   Urologie, Charité – Universitätsmedizin Berlin, Berlin, Deutschland
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Erratum: Management des metastasierten hormonsensitiven ProstatakarzinomsAktuelle Urol eFirst
DOI: 10.1055/a-2110-9321

Zusammenfassung

Aufgrund der überzeugenden Datenlage mit einer Steigerung des Gesamtüberlebens (OS) wird in den aktuellen nationalen und internationalen europäischen Leitlinien (S3, ESMO, EAU) eine Kombinationstherapie aus ADT und Docetaxel oder den neuen Hormonsubstanzen Abirateron (plus Prednison/Prednisolon), Apalutamid oder Enzalutamid als Standard für mHSPC-Patienten in gutem Allgemeinzustand (ECOG 0–1) empfohlen. Gemäß Zulassung kann Abirateron/P nur beim neu diagnostizierten (de novo) high-risk mHSPC zum Einsatz kommen. Für Docetaxel besteht beim mHSPC kein einschränkender Zulassungsstatus, jedoch wird in der aktuellen S3-Leitlinie im Empfehlungsgrad hinsichtlich Tumorlast differenziert: Während bei Patienten mit hoher Tumorlast (high-volume mHSPC) eine Soll-Empfehlung besteht, wird bei niedriger Tumorlast (low-volume mHSPC) aufgrund der uneinheitlichen Daten nur eine abgeschwächte Kann-Empfehlung gegeben. Apalutamid und Enzalutamid stellen für ein breites Spektrum von mHSPC-Patienten eine Option dar.

In der klinischen Praxis kann es schwierig sein, einen Progress unter einer laufenden Therapie zu erfassen. In der Regel kommt es zuerst zum PSA-Progress und schließlich auch zum radiologischen und klinischen Progress. Als Grundlage für einen Therapiewechsel in der hormonsensitiven Situation gilt das Auftreten der nach der EAU-Leitlinie definierten Kastrationsresistenz. In der kastrationsresistenten Situation sollte eine Progression gemäß PCWG3-Kriterien der Prostate Cancer Clinical Trials Working Group vorliegen, sodass grundsätzlich zumindest 2 der 3 Kriterien (PSA-Progress, radiologischer Progress, klinische Verschlechterung) gegeben sind, um von einem klinisch relevanten Progress auszugehen und die Therapie zu wechseln. Da es sich beim fortgeschrittenen Prostatakarzinom jedoch um eine sehr heterogene Erkrankung handelt, muss die Entscheidung zum Therapiewechsel in der klinischen Praxis letztendlich individuell getroffen werden.

Abstract

Based on convincing data with an increase in overall survival (OS), the current national and international European Guidelines (S3, ESMO, EAU) recommend a combination therapy with ADT plus Docetaxel or plus the next-generation antiandrogens abiraterone (plus prednisone/prednisolone), apalutamide or enzalutamide as standard treatment for mHSPC patients with a good performance status (ECOG 0–1). Abiraterone received approval only for use in patients with newly diagnosed (de novo) high-risk mHSPC. There is no restrictive approval status for docetaxel in mHSPC. However, the current S3 guideline differentiates in the level of recommendation with regard to tumour volume: a “strong” recommendation is given in high-volume mHSPC, while only a “may” recommendation is given for low-volume mHSPC due to inconsistent data. Apalutamide and enzalutamide are treatment options in a broad range of mHSPC patients.

It can be difficult in clinical practice to determine disease progression under ongoing treatment. Generally, a rising PSA level is the first sign of progression, followed by radiographic and clinical progress. In the hormone-sensitive situation, the decision of when to change treatment can be based on the progression to castration-resistant prostate cancer as defined by the EAU guidelines; in the castration-resistant situation, it can be based on progression as per PCWG3 criteria of the Prostate Cancer Clinical Trials Working Group. At least two of the three criteria (PSA progression, radiographic progression, and clinical deterioration) should be met to determine progression and to change treatment. However, since advanced prostate cancer is a very heterogeneous disease, the decision to change treatment in clinical practice must ultimately be made on a case-by-case basis.

Schlüsselwörter

Prostatakarzinom - Metastasen - Hormontherapie

Keywords

prostate cancer - metastasis - hormonal therapy


Publication History

Received: 21 September 2022

Accepted after revision: 07 March 2023

Article published online:
26 May 2023

© 2023. Thieme. All rights reserved.

Georg Thieme Verlag KG
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  • Literatur

  • 1 S3-Leitlinie zur Früherkennung, Diagnose und Therapie der verschiedenen Stadien des Prostatakarzinoms. Version 6.2 – Oktober 2021 AWMF – Registernummer: 043/022OL. Accessed January 18, 2022 at: https://www.leitlinienprogramm-onkologie.de/leitlinien/prostatakarzinom
    PubMed
  • 2 Mottet M. et al. EAU-Guidelines Prostate Cancer 2021. Accessed January 18, 2022 at: https://uroweb.org/guideline/prostate-cancer/
    PubMed
  • 3 Parker C. et al. Prostate cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 2020; 31: 1119-1134
    CrossrefPubMedSearch in Google Scholar
  • 4 Kyriakopoulos CE. et al. Chemohormonal Therapy in Metastatic Hormone-Sensitive Prostate Cancer: Long-Term Survival Analysis of the Randomized Phase III E3805 CHAARTED Trial. J Clin Oncol 2018; 36: 1080-1087
    CrossrefPubMedSearch in Google Scholar
  • 5 Fizazi M. et al. Abiraterone acetate plus prednisone in patients with newly diagnosed high-risk metastatic castration-sensitive prostate cancer (LATITUDE): final overall survival analysis of a randomised, double-blind, phase 3 trial. Lancet Oncol 2019; 20: 686-700
    CrossrefPubMedSearch in Google Scholar
  • 6 Chi KN. et al. Apalutamide for Metastatic, Castration-Sensitive Prostate Cancer. N Engl J Med 2019; 381: 13-24
    CrossrefPubMedSearch in Google Scholar
  • 7 Chi KN. et al. Apalutamide in Patients With Metastatic Castration-Sensitive Prostate Cancer: Final Survival Analysis of the Randomized, Double-Blind, Phase III TITAN Study. J Clin Oncol 2021; 39: 2294-2303
    CrossrefPubMedSearch in Google Scholar
  • 8 Armstrong AJ. et al. ARCHES: A Randomized, Phase III Study of Androgen Deprivation Therapy With Enzalutamide or Placebo in Men With Metastatic Hormone-Sensitive Prostate Cancer. J Clin Oncol 2019; 37: 2974-2986
    CrossrefPubMedSearch in Google Scholar
  • 9 Davies ID. et al. Enzalutamide with Standard First-Line Therapy in Metastatic Prostate Cancer. N Engl J Med 2019; 381: 121-131
    CrossrefPubMedSearch in Google Scholar
  • 10 Aktuelle Fachinformation Zytiga®.
    PubMed
  • 11 Aktuelle Fachinformation Taxotere®.
    PubMed
  • 12 Schweizer MT. et al. Docetaxel-related toxicity in metastatic hormone-sensitive and metastatic castration-resistant prostate cancer. Med Oncol 2016; 33: 77
    CrossrefPubMedSearch in Google Scholar
  • 13 Khalaf DJ. et al. Optimal sequencing of enzalutamide and abiraterone acetate plus prednisone in metastatic castration-resistant prostate cancer: a multicentre, randomised, open-label, phase 2, crossover trial. Lancet Oncol 2019; 20: 1730-1739
    CrossrefPubMedSearch in Google Scholar
  • 14 Mori K. et al. Sequential therapy of abiraterone and enzalutamide in castration-resistant prostate cancer: a systematic review and meta-analysis. Prostate Cancer Prostatic Dis 2020; 23: 539-548
    CrossrefPubMedSearch in Google Scholar
  • 15 Aktuelle Fachinformation Erleada®.
    PubMed
  • 16 Aktuelle Fachinformation Xtandi.
    PubMed
  • 17 Argawal N. et al. Time to second progression (PFS2) in patients (pts) from TITAN with metastatic castration-sensitive prostate cancer (mCSPC) by first subsequent therapy (hormonal vs. taxane). J Clin Oncol 2020; 38 (Suppl. 6): abstr 82 & oral presentation. GU ASCO. 2020
    PubMedSearch in Google Scholar
  • 18 Chi KN. et al. Androgen receptor (AR) aberrations in patients (Pts) with metastatic castration-sensitive prostate cancer (mCSPC) treated with apalutamide (APA) plus androgen deprivation therapy (ADT) in TITAN. ESMO 2019, Abstract 883P & poster presentation.
    PubMed
  • 19 Thelen P. et al. Mechanisms of Resistance in Antihormone Therapies of Advaced Prostate Cancer. Aktuelle Urol 2016; 47: 79-85
    PubMedSearch in Google Scholar
  • 20 Scher HI. et al. Trial Design and Objectives for Castration-Resistant Prostate Cancer: Updated Recommendations from the Prostate Cancer Clinical Trials Working Group 3. J Clin Oncol 2016; 34: 1402-1418
    Search in Google Scholar
  • 21 Smith MR. et al. Apalutamide Treatment and Metastasis-free Survival in Prostate Cancer. N Engl J Med 2018; 378: 1408-1418
    Search in Google Scholar
  • 22 Hussain M. et al. Enzalutamide in Men with Nonmetastatic, Castration-Resistant Prostate Cancer. N Engl J Med 2018; 378: 2465-2474
    CrossrefPubMedSearch in Google Scholar
  • 23 Fizazi K. et al. Darolutamide in Nonmetastatic, Castration-Resistant Prostate Cancer. N Engl J Med 2019; 380: 1235-1246
    Search in Google Scholar
  • 24 Fizazi M. et al. Abiraterone plus Prednisone in Metastatic, Castration-Sensitive Prostate Cancer. N Engl J Med 2017; 377: 352-360
    CrossrefPubMedSearch in Google Scholar
  • 25 Sweeney CJ. et al. Chemohormonal therapy in metastatic hormone-sensitive prostate cancer. N Engl J Med 2015; 373: 737-746
    Search in Google Scholar
  • 26 Fendler WP. et al. PSMA-PET Results in a Nonmetastatic Castration-Resistant Prostate Cancer SPARTAN-Like Population That Is Negative by Conventional Imaging. 19th Annual Meeting of the Society of Urologic Oncology 2018, Poster 202.
    PubMed
  • 27 Bryce AH. et al. Radiographic progression with non-rising PSA in metastatic castration-resistant prostate cancer: Post-hoc analysis of PREVAIL. Prostate Cancer Prostatic Dis 2017; 20: 221-227
    CrossrefPubMedSearch in Google Scholar
  • 28 Ryan C. et al. Abiraterone acetate plus prednisone versus placebo plus prednisone in chemotherapy-naive men with metastatic castration-resistant prostate cancer (COU-AA-302): final overall survival of a randomised, double-blind, placebo-controlled phase 3 study. Supplementary Appendix, Table 1. Lancet Oncol 2015; 16: 152-160
    CrossrefPubMedSearch in Google Scholar