Lutetium-177 PSMA Radioligand Therapy of Metastatic Castration-Resistant Prostate Cancer: Safety and Efficacy

Abstract

Aim: The objective of this study was to analyze the safety and efficacy of ¹⁷⁷Lu-labeled DOTAGA-based prostate specific membrane antigen (PSMA) ligand ¹⁷⁷Lu-DOTAGA-(I-y)fk(Sub-KuE) (¹⁷⁷Lu-PSMA) in patients with metastatic castration-resistant prostate cancer (mCRPC). Methods: Fifty-six mCRPC patients underwent PSMA radioligand therapy (RLT) with ¹⁷⁷Lu-PSMA. ⁶⁸Ga-PSMA-HBED-CC (⁶⁸Ga-PSMA) PET/CT was used for patient selection and follow-up after PSMA-RLT. Hematological status, renal function and serum prostate specific antigen (PSA) levels were documented before and after therapy. Dosimetry was performed in 30 patients. Results: ¹⁷⁷Lu-PSMA demonstrated high absorbed tumor doses (median, 3.3 mGy/MBq) as compared to normal organs. Parotid glands received higher doses (1.3 mGy/MBq) than kidneys (0.8 mGy/MBq). All patients tolerated the therapy without any acute adverse effects. Except mild reversible xerostomia in two patients, no long-term side effect was observed. There was a small, but statistically significant reduction in erythrocyte and leukocyte counts, of which only the erythrocytes decreased slightly below the normal range. No thrombocytopenia occurred. The severity of pain significantly reduced in 2/6 (33.33%) patients. Decrease in PSA was noted in 45/56 (80.3%) patients. In 25 patients, followed up at least 6 months after ≥2 PSMA-RLT cycles, molecular response evaluation (⁶⁸Ga-PSMA PET/CT) revealed partial remission (PR) in 14, stable disease (SD) in 2 and progressive disease (PD) in 9 patients. Contrast-enhanced CT exhibited PR in 5, SD in 13, and PD in 7 patients. The median progression-free survival was 13.7 months, and the median overall survival was not reached at follow-up of 28 months. Conclusion: PSMA-RLT with ¹⁷⁷Lu-PSMA is feasible, safe and effective in end-stage progressive mCRPC with appropriate selection and follow-up of patients by ⁶⁸Ga-PSMA PET/CT applying the concept of Theranostics.