Overview of selected completed prospective studies on PSMA-targeted radioligand therapy with [¹⁷⁷Lu]Lu-PSMA-617 in metastatic castration-resistant prostate cancer

Abstract

Background

Theranostics in nuclear oncology combines diagnostic and therapeutic procedures using radiotracers to target tumor cells. Prostate-specific membrane antigen (PSMA) is a key target in metastatic prostate cancer, and the radioligand [¹⁷⁷Lu]Lu-PSMA-617, which binds to PSMA, has shown promising results in treating metastatic castration-resistant prostate cancer (mCRPC), leading to its approval by the European Medicines Agency in 2022.

Method

In this narrative review, the current evidence of [¹⁷⁷Lu]Lu-PSMA-617 in mCRPC was discussed in the context of selected studies and the joint EANM/SNMMI guidelines for Lutetium-177-labeled PSMA-targeted radioligand therapy.

Results

The use of [¹⁷⁷Lu]Lu-PSMA-617 for post-chemotherapy mCRPC is supported by substantial evidence from the phase II TheraP and the phase III VISION trials, demonstrating its safety and efficacy. The theranostic approach identifies patients likely to benefit from [¹⁷⁷Lu]Lu-PSMA-617, which is effective only in tumors with sufficient PSMA expression, as detected by PSMA-ligand PET/CT, which is also used for response assessment.

Conclusion

The success of [¹⁷⁷Lu]Lu-PSMA-617 in post-chemotherapy mCRPC patients has led to further ongoing studies evaluating its use earlier in the treatment sequence, prior to chemotherapy. To ensure beneficial treatment outcome, adequate patient selection and evaluation of imaging-based response through PSMA-ligand PET/CT is necessary.

Key Points

• Indications for [¹⁷⁷Lu]Lu-PSMA-617 are based on the TheraP and VISION clinical trials.

• Adequate patient selection using PSMA-ligand PET/CT is essential for beneficial outcomes.

• Response evaluation is based on imaging, PSA levels, and the patient’s clinical condition.

Citation Format

• Karimzadeh A, Lehnert W, Koehler D et al. Overview of selected completed prospective studies on PSMA-targeted radioligand therapy with [¹⁷⁷Lu]Lu-PSMA-617 in metastatic castration-resistant prostate cancer. Rofo 2025; DOI 10.1055/a-2514-4523

Zusammenfassung

Hintergrund

Theranostik in der nuklearen Onkologie kombiniert diagnostische und therapeutische Verfahren unter Verwendung von Radiotracern, um Tumorzellen gezielt anzugreifen. Das prostata-spezifische Membranantigen (PSMA) ist eine wichtige Zielstruktur des metastasierten Prostatakrebs, und der Radioligand [¹⁷⁷Lu]Lu-PSMA-617, das an PSMA bindet, hat vielversprechende Ergebnisse bei der Behandlung von metastasiertem kastrationsresistentem Prostatakrebs (mCRPC) gezeigt, was zur Zulassung durch die Europäische Arzneimittel-Agentur im Jahr 2022 führte.

Methode

In diesem narrativen Review wurde die aktuelle Evidenz von [¹⁷⁷Lu]Lu-PSMA-617 bei mCRPC im Kontext ausgewählter Studien und der gemeinsamen EANM/SNMMI-Leitlinien zur Lutetium-177-markierten PSMA-gerichteten Radioligandentherapie diskutiert.

Ergebnisse

Die Anwendung von [¹⁷⁷Lu]Lu-PSMA-617 bei mCRPC nach Chemotherapie wird durch umfangreiche Evidenz aus der Phase-II-TheraP- und der Phase-III-VISION-Studie unterstützt, die seine Sicherheit und Wirksamkeit belegen konnten. Der theranostische Ansatz identifiziert Patienten, die wahrscheinlich von [¹⁷⁷Lu]Lu-PSMA-617 profitieren. Dieses ist nur bei Tumoren mit ausreichender PSMA-Expression wirksam, wie durch PSMA-Liganden PET/CT nachgewiesen wird, die auch für die Beurteilung des Ansprechens verwendet wird.

Schlussfolgerung

Der Erfolg von [¹⁷⁷Lu]Lu-PSMA-617 bei Patienten mit mCRPC nach Chemotherapie hat zu weiteren laufenden Studien geführt, die den Einsatz dieses Therapeutikums früher im Behandlungsverlauf, noch vor der Chemotherapie, evaluieren. Um einen Behandlungserfolg zu erreichen, sind eine adäquate Patientenauswahl und die Bewertung des bildgebungsbasierten Ansprechens durch PSMA-Liganden PET/CT erforderlich.

Kernaussagen

• Die Indikationen für [¹⁷⁷Lu]Lu-PSMA-617 basieren auf den klinischen Studien TheraP und VISION.

• Eine angemessene Patientenauswahl mittels PSMA-Liganden PET/CT ist entscheidend für vorteilhafte Behandlungsergebnisse.

• Die Bewertung des Ansprechens basiert auf Bildgebung, PSA-Werten und dem klinischen Patientenzustand.

Keywords

prostate-specific membrane antigen (PSMA) - radioligand therapy (RLT) - metastatic castration-resistant prostate cancer (mCRPC) - ¹⁷⁷Lu]Lu-PSMA-617

Publication History

Received: 14 June 2024

Accepted after revision: 04 January 2025

Article published online:
06 August 2025

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