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

Amina Banda; Bastiaan M Privé; Youssra Allach; Maike J M Uijen; Steffie M B Peters; Cato C Loeff; Martin Gotthardt; Constantijn H J Muselaers; J Alfred Witjes; Inge M van Oort; J P Michiel Sedelaar; Harm Westdorp; Niven Mehra; Fadi Khreish; Samer Ezziddin; Amir Sabet; Michael C Kreissl; Thomas Winkens; Philipp Seifert; Marcel J R Janssen; Willemijn A M van Gemert; James Nagarajah

doi:10.3390/cancers15010297

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

Cancers (Basel). 2022 Dec 31;15(1):297. doi: 10.3390/cancers15010297.

Authors

Amina Banda¹, Bastiaan M Privé¹, Youssra Allach¹, Maike J M Uijen¹, Steffie M B Peters¹, Cato C Loeff¹, Martin Gotthardt¹, Constantijn H J Muselaers¹, J Alfred Witjes², Inge M van Oort², J P Michiel Sedelaar², Harm Westdorp³, Niven Mehra³, Fadi Khreish⁴, Samer Ezziddin⁴, Amir Sabet⁵, Michael C Kreissl⁶, Thomas Winkens⁷, Philipp Seifert⁷, Marcel J R Janssen¹, Willemijn A M van Gemert¹, James Nagarajah¹

Affiliations

¹ Department of Radiology and Nuclear Medicine, Radboud University Medical Center, P.O. Box 9101, 6525 GA Nijmegen, The Netherlands.
² Department of Medical Oncology, Radboud University Medical Center, 6500 HB Nijmegen, The Netherlands.
³ Department of Urology and Oncology, Radboud Universiteit Medical Center, 6525 GA Nijmegen, The Netherlands.
⁴ Department of Nuclear Medicine, University of Saarland, D-66421 Homburg, Germany.
⁵ University Hospital, Department of Nuclear Medicine, Goethe University Frankfurt, 60590 Frankfurt am Main, Germany.
⁶ Division of Nuclear Medicine, Department of Radiology and Nuclear Medicine, Magdeburg University Hospital, 39120 Magdeburg, Germany.
⁷ Clinic for Nuclear Medicine, University Hospital of Jena, 07743 Jena, Germany.

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 [¹⁷⁷Lu]Lu-PSMA- (¹⁷⁷Lu-PSMA) or [²²⁵Ac]Ac-PSMA-radioligand treatment (²²⁵Ac-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 ¹⁷⁷Lu-PSMA and/or ²²⁵Ac-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 ¹⁷⁷Lu-PSMA radioligand and two patients received tandem treatment with both ¹⁷⁷Lu-PSMA and ²²⁵Ac-PSMA radioligands. Patients received a median of 2 treatment cycles (range 1-6) and a median activity of 6.2 GBq ¹⁷⁷Lu-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 ²²⁵Ac-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.

Keywords: Actinium-225; Lutetium-177; PSMA radioligand therapy; early stage; prostate cancer.

Grants and funding

This research received no external funding.