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PSMA-RLT in Patients with Metastatic Hormone-Sensitive Prostate Cancer: A Retrospective Study

SIMPLE SUMMARY: Prostate-specific membrane antigen-direct radioligand therapy is a novel treatment for patients with castration-resistant prostate cancer. Yet, given the mode of action of PSMA-RLT, it is postulated that in early disease prostate cancer settings, e.g. hormone-sensitive, can also bene...

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Detalles Bibliográficos
Autores principales: Banda, Amina, Privé, Bastiaan M., Allach, Youssra, Uijen, Maike J. M., Peters, Steffie M. B., Loeff, Cato C., Gotthardt, Martin, Muselaers, Constantijn H. J., Witjes, J. Alfred, van Oort, Inge M., Sedelaar, J. P. Michiel, Westdorp, Harm, Mehra, Niven, Khreish, Fadi, Ezziddin, Samer, Sabet, Amir, Kreissl, Michael C., Winkens, Thomas, Seifert, Philipp, Janssen, Marcel J. R., van Gemert, Willemijn A. M., Nagarajah, James
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9818570/
https://www.ncbi.nlm.nih.gov/pubmed/36612293
http://dx.doi.org/10.3390/cancers15010297
Descripción
Sumario:SIMPLE SUMMARY: Prostate-specific membrane antigen-direct radioligand therapy is a novel treatment for patients with castration-resistant prostate cancer. Yet, given the mode of action of PSMA-RLT, it is postulated that in early disease prostate cancer settings, e.g. hormone-sensitive, can also benefit from this treatment. In this retrospective study, the safety and efficacy was investigated of two PSMA-RLT schemes: monotherapy with 177Lu-PSMA and 177Lu-PSMA in combination with 225Ac-PSMA in twenty patients with early stage metastatic prostate cancer. The treatment appeared safe with limited and mainly transient side effects, also on a longer term follow-up, with encouraging efficacy for twenty early-stage metastatic prostate cancer. ABSTRACT: Background: Prostate-specific membrane antigen (PSMA)-directed radioligand therapy (RLT) is a novel treatment for patients with castration-resistant prostate cancer (CRPC). Given the mode of action, patients in an earlier disease stage, such as hormone-sensitive prostate cancer (HSPC), are also likely to benefit from [(177)Lu]Lu-PSMA- ((177)Lu-PSMA) or [(225)Ac]Ac-PSMA-radioligand treatment ((225)Ac-PSMA). In this retrospective study, we analyzed the safety and efficacy of PSMA-RLT in early-stage and hormone-sensitive metastatic prostate cancer patients. Methods: A retrospective study was performed in patients who received (177)Lu-PSMA and/or (225)Ac-PSMA with early-stage metastatic prostate cancer. The primary outcome parameter evaluated in this study was the progression-free survival (PFS) after PSMA-RLT and toxicity according to the Common Terminology Criteria for Adverse Events. Secondary outcome parameters were prostate-specific antigen (PSA) response and the date of onset of CRPC state. Results: In total, 20 patients were included of which 18 patients received (177)Lu-PSMA radioligand and two patients received tandem treatment with both (177)Lu-PSMA and (225)Ac-PSMA radioligands. Patients received a median of 2 treatment cycles (range 1–6) and a median activity of 6.2 GBq (177)Lu-PSMA per cycle (interquartile range (IQR) 5.2–7.4 GBq). PSMA-RLT was overall well-tolerated. The most common grade 1–2 side effects were xerostomia (n = 6) and fatigue (n = 8), which were only temporarily reported. One patient that received (225)Ac-PSMA developed grade 3–4 bone marrow toxicity. The median PFS was 12 months (95% confidence interval (CI), 4.09–19.9 months). Seventeen (85%) patients had a ≥50% PSA response following PSMA-RLT. One patient developed CRPC 9 months following PSMA-RLT. Conclusions: In this small cohort study, PSMA-RLT appeared safe and showed encouraging efficacy for (metastasized) early-stage and hormone-sensitive prostate cancer patients. Prospective studies are awaited and should include long-term follow-up.