Treatment outcome and identification of factors influencing overall survival after Lu-177-PSMA-617 radioligand therapy in metastatic prostate cancer

Abstract

Objective To examine the clinical benefit of Lu-177-PSMA-617 radioligand therapy for patients with metastatic castration-resistant prostate cancer (mCRPC).

Patients and Methods Between November 2014 and December 2018, a total of 56 consecutive patients (median age 69.5 years; range 55–84 years) with mCRPC were included in this retrospective analysis. Patients received between 1 and 4 therapy cycles with a mean activity of 6.8 GBq per cycle. Biochemical response was evaluated using Prostate Cancer Working Group Criteria 3 (PCWG 3). Survival was assessed using Kaplan-Meier estimates and Cox proportional hazards regression analysis. This retrospective study was approved by the local ethics committee.

Results A total of 139 treatment cycles with Lu-177-PSMA-617 were performed. A decline of 50% or more of prostate-specific antigen (PSA) level occurred in 54% and a PSA decline of any amount in 65% of patients. The estimated median overall survival (OS) was 16 months, in the chemotherapy subgroup 14 months. A longer OS was associated with a PSA-decline ≥50%, more than 2 cycles of therapy, cumulative activity >15 GBq and an initial alkaline phosphatase ≤ 220 [U/l]. These identified predictors remained significant on uni- and multivariate Cox regression analysis. Moreover, 40% of the patients who were non-responders after the first therapy cycle turned into responders after the second one.

Conclusion PSA-decline ≥50%, a cumulative activity >15 GBq and an initial alkaline phosphatase ≤ 220 [U/l] were identified as key predictors of prolonged OS in patients with mCRPC. In contrast rapid clinical deterioration mostly due to skeletal carcinomatosis resulted in early treatment failure.

Zusammenfassung

Ziel Es sollte der klinische Nutzen der Lu-177-PSMA-617-Radioligandentherapie bei Patienten mit metastasiertem kastrationsresistentem Prostatakrebs (mCRPC) untersucht werden.

Patienten und Methoden In diese retrospektive Analyse zwischen November 2014 und Dezember 2018 wurden insgesamt 56 konsekutive Patienten (medianes Alter 69,5 Jahre; Bereich 55–84 Jahre) mit mCRPC eingeschlossen. Die Patienten erhielten zwischen 1 und 4 Therapiezyklen mit einer mittleren Aktivität von 6,8 GBq pro Zyklus. Das biochemische Ansprechen wurde anhand der Kriterien der „Prostate Cancer Working Group“ (PCWG 3) bewertet. Das Überleben wurde mittels Kaplan-Meier-Schätzer und einer proportionalen Cox-Hazard-Regressionsanalyse bewertet. Diese retrospektive Studie wurde von der zuständigen Ethikkommission genehmigt.

Ergebnisse Insgesamt wurden 139 Behandlungszyklen mit Lu-177-PSMA-617 durchgeführt. Eine Abnahme des Prostata-spezifischen Antigens (PSA) um 50 % oder mehr trat bei 54 % und eine PSA-Abnahme in beliebiger Höhe bei 65 % der Patienten auf. Das geschätzte mediane Gesamtüberleben (OS) betrug 16 Monate, in der Chemotherapie-Untergruppe 14 Monate. Ein längeres OS war verbunden mit einem PSA-Abfall ≥50%, mehr als 2 Therapiezyklen, einer kumulativen Aktivität >15 GBq und einem initialen Wert für alkalischen Phosphatase ≤220 [U/l]. Diese identifizierten Prädiktoren blieben in der uni- und multivariaten Cox-Regressionsanalyse signifikant. Außerdem wurden 40 % der Patienten, die nach dem ersten Therapiezyklus nicht auf die Therapie ansprachen (Non-Responder), nach dem zweiten Zyklus zu Respondern.

Schlussfolgerung Ein PSA-Abfall von ≥50%, eine kumulative Aktivität von >15 GBq und ein initialer Wert für alkalische Phosphatase von ≤220 [U/l] wurden als Schlüsselprädiktoren für ein längeres OS bei Patienten mit mCRPC identifiziert. Im Gegensatz dazu führte eine rasche klinische Verschlechterung, meist aufgrund einer Skelettkarzinose, zu einem frühen Therapieversagen.

Schlüsselwörter

Prostatakarzinom - Lu-177-PSMA-617 - Radioligandentherapie

Keywords

prostate carcinoma - Lu-177-PSMA-617 - radioligand therapy

Publikationsverlauf

Eingereicht: 09. Juni 2021

Angenommen nach Revision: 14. Oktober 2021

Artikel online veröffentlicht:
16. Dezember 2021

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