177Lu-labeled prostate-specific membrane antigen radioligand therapy of metastatic castration-resistant prostate cancer: Safety and efficacy

Abstract

The objective of this study was to analyze the safety and efficacy of the 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-(N′N′-bis-[2-hydroxy-5-(carboxyethyl)benzyl]ethylenediamine-N′N′-diacetic acid) (68Ga-PSMA) PET/CT was used for patient selection and follow-up after PSMA RLT. Hematologic status, renal function, and serum prostate-specific antigen 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) compared with the levels in 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 for mild reversible xerostomia in 2 patients, no long-term side effects were observed. There was a small but statistically significant reduction in erythrocyte and leukocyte counts; only the reduction in erythrocyte counts decreased slightly below the reference range. No thrombocytopenia occurred. The severity of pain was significantly reduced in 2 of 6 patients (33.3%). A decrease in prostate-specific antigen levels was noted in 45 of 56 patients (80.4%). Of 25 patients monitored for at least 6 mo after 2 or more PSMA RLT cycles, a molecular response evaluation (68Ga-PSMA PET/CT) revealed partial remission in 14, stable disease in 2, and progressive disease in 9 patients. Contrast-enhanced CT revealed partial remission in 5, stable disease in 13, and progressive disease in 7 patients. The median progression-free survival was 13.7 mo, and the median overall survival was not reached during follow-up for 28 mo. 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 through application of the concept of theranostics.