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.
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.
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.
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.
Cancers. 2022 Dec 31*** epublish ***
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
Department of Radiology and Nuclear Medicine, Radboud University Medical Center, P.O. Box 9101, 6525 GA Nijmegen, The Netherlands., Department of Medical Oncology, Radboud University Medical Center, 6500 HB Nijmegen, The Netherlands., Department of Urology and Oncology, Radboud Universiteit Medical Center, 6525 GA Nijmegen, The Netherlands., Department of Nuclear Medicine, University of Saarland, D-66421 Homburg, Germany., University Hospital, Department of Nuclear Medicine, Goethe University Frankfurt, 60590 Frankfurt am Main, Germany., Division of Nuclear Medicine, Department of Radiology and Nuclear Medicine, Magdeburg University Hospital, 39120 Magdeburg, Germany., Clinic for Nuclear Medicine, University Hospital of Jena, 07743 Jena, Germany.