Abstract
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Introduction: 223Radium-dichloride (223Ra) is routinely used in bone metastatic castration-resistant prostate cancer. Radioligand therapy with 177lutetium-PSMA-617 (177Lu-PSMA-RLT) has proved an effective and well tolerated option for patients failing standard therapies including 223Ra. However, the feasibility of immediate onset of 177Lu-PSMA-RLT after 223Ra has not been investigated yet. We retrospectively assessed the safety and outcome of 177Lu-PSMA-RLT starting within 3 months after 223Ra.
Methods: 30 patients with progressive disease who started 177Lu-PSMA-RLT within 5 ± 3 weeks after the last 223Ra administration were analyzed. Patients received a median of 4 (range 3-6) 223Ra injections followed by 4 ± 3 cycles of 6.3 ± 2.1 GBq 177Lu-PSMA. The mean cumulative activity of 177Lu-PSMA was 30.7 ± 21.6 GBq. 18F-NaF-PET/CT, bone scan and 68Ga-PSMA PET/CT were used for response and tumor burden assessment based on PROMISE miTNM classification1. Hematological parameters were measured at baseline, prior to and 2 to 4 weeks after each administration, and throughout follow-up. Toxicity was classified using Common Terminology Criteria for Adverse Events v5.0. Correlations of skeletal tumor burden (disseminiated/diffuse vs. oligometastatic) and cumulated activity with the treatment induced hematotoxicity were examined with Spearman's rank correlation coefficient. Kaplan-Meier curve method was used for survival analysis. Results: 25 patients had mild (grade 1) and 3 patients moderate (grade 2) bone marrow impairment at baseline. 177Lu-PSMA-RLT induced significant hematotoxicity (grade 3-4) necessitating blood transfusion in 4 patients (13.3 %) and led to treatment discontinuation in 2 patients. Moderate renal function loss of grade 2 was seen in 7 patients but no significant nephrotoxicity occurred. Response to 177Lu-PSMA-RLT consisted of partial response in 14 patients (46.7 %), stable disease in 1 patient (3.3 %), and progressive disease in 15 patients (50.0 %). Median progression free survival (PFS) was 10 months (95 % CI 6-14) and median overall survival was 20 months (95 % CI 13-27). Disease control resulted in significantly prolonged overall survival (37 vs. 16 months, p<0.001) whereas disseminated/diffuse bone involvement (n=12) at baseline was associated with a significantly shorter overall survival (36 vs. 14 months, p<0.002). Conclusion: Radioligand therapy with 177Lu-PSMA can be initiated as early as 12 weeks after treatment with 223Ra with an acceptable risk profile and may prolong survival especially in patients with oligometastatic bone involvement. 1. Eiber M, Herrmann K, Calais J, et al. Prostate Cancer Molecular Imaging Standardized Evaluation (PROMISE): Proposed miTNM Classification for the Interpretation of PSMA-Ligand PET/CT. Journal of nuclear medicine : official publication, Society of Nuclear Medicine. 2018;59(3):469-478.