Molekulare Testung des Prostatakarzinoms: wann, wie und mit welcher Konsequenz?

Zusammenfassung

Das metastasierte Prostatakarzinom ist eine heterogene Erkrankung. Bislang basiert die Behandlungsentscheidung meist auf der Tumorausdehnung und -symptomlast, Begleiterkrankungen und dem Patientenwunsch. Molekularpathologische Aspekte fließen nur selten ein.

Kostenrückgang und zunehmende Verbreitung des Next Generation Sequencing (NGS) haben zu einer Zunahme der molekularen Testung und einem besseren Verständnis der Bedeutung molekularer Alterationen für die Entstehung und Ausbreitung des Prostatakarzinoms geführt. Eine konsequentere Testung konstitutioneller Genveränderungen („Keimbahntestung“) deckt hereditäre Prädispositionen auf. Nach der Zulassung von Olaparib zur Therapie BRCA1/2 mutierter, kastrationsresistenter Prostatakarzinome befinden sich weitere zielgerichtete Therapieansätze in der Entwicklung.

In unserem Übersichtsartikel geben wir einen Überblick zur aktuellen molekularen Testung beim Prostatakarzinom und diskutieren mögliche Konsequenzen.

Abstract

Metastatic prostate cancer is a heterogeneous disease. To date, however, treatment decisions are often based on the extent and symptom burden of the tumour, concomitant diseases, and the patient’s wishes. Molecular pathology aspects are rarely taken into account.

Declining costs and the increasing use of next-generation sequencing (NGS) have led to an increase in molecular testing and a better understanding of the significance of molecular alterations for the development and spread of prostate cancer. More consistent germline testing reveals hereditary predispositions.

Following the approval of olaparib for the treatment of BRCA1/2 mutated, castration-resistant prostate cancer, further targeted therapeutic approaches are currently under development.

In our review article, we provide an overview of current molecular testing in prostate cancer and discuss possible consequences.

Fazit für die Praxis

• Das Prostatakarzinom ist eine heterogene Erkrankung.

• Eine Testung konstitutioneller Genalterationen (Keimbahntestung) soll allen Patienten angeboten werden, die die Kriterien der NCCN-Leitlinie erfüllen.

• Aktuell erfolgt die Behandlungsentscheidung in der metastasierten Situation häufig noch unabhängig von molekularen Markern.

• Aufgrund der schlechteren Prognose und dem geringeren Ansprechen der BRCA1/2+ Patienten auf Standardtherapien empfiehlt sich eine somatische Testung frühzeitig bei Progress unter dem ersten ARPI.

• Kombinationstherapien mit ARPI- und PARP-Inhibitoren können prinzipiell unabhängig vom HRR-Status eingesetzt werden, zeigen allerdings bei HRR+-Patienten, insbesondere BRCA1/2+-Patienten die höchste Effektivität.

• Genalterationen von TP53, PTEN, RB1 und FOXA1 gehen mit einem aggressiven Tumorverlauf und einem mutmaßlich schlechteren Ansprechen auf Standardtherapien einher.

• Eine umfassende molekularpathologische Analyse kann über die ZPM angeboten werden, wenn von einer baldigen Ausschöpfung der Standardtherapien auszugehen ist. Hier sollen potenziell targetierbare Läsionen identifiziert werden.

• Zielgerichtete Therapiestrategien für das Prostatakarzinom befinden sich in der klinischen Testung.

• Künftig dürften Therapieentscheidungen zunehmend auf dem individuellen molekularen Profil der Patienten beruhen.

Schlüsselwörter

Somatische Testung - Keimbahntestung - konstitutionelle Genveränderungen - zielgerichtete Therapie - PARP-Inhibitoren

Keywords

Somatic testing - germline testing - constitutional gene alterations - targeted therapy - PARP inhibitors

Publication History

Received: 05 February 2024

Accepted: 06 February 2024

Article published online:
27 March 2024

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