Management des metastasierten hormonsensitiven Prostatakarzinoms

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

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