BACKGROUND: We investigated the response rate and degree of toxicity of a second course of three cycles of [177Lu]Lu-PSMA radioligand therapy (PSMA-RLT) every 4 weeks in mCRPC patients. METHODS: Forty-three men (71.5 ± 6.6 years, median PSA 40.8 (0.87-1358 µg/L)) were studied. The response was based on the PSA level 4 weeks after the third cycle. The laboratory parameters before and one month after the last cycle were compared. Kaplan-Meier methods were used to estimate the progression-free survival (PFS) and overall survival (OS), and the Cox regression model was performed to find predictors of survival. RESULTS: Twenty-six patients (60.5%) exhibited a PSA reduction (median PSA declined from 40.8 to 20.2, range 0.6-1926 µg/L, p = 0.002); 18 (42%) and 8 (19%) patients showed a PSA decline of ≥50% and ≥80%, respectively. The median OS and PFS were 136 and 31 weeks, respectively. The patients with only lymph node metastases survived longer (p = 0.02), whereas the patients with bone metastases had a shorter survival (p = 0.03). In the multivariate analysis, only the levels of PSA prior to the therapy remained significant for OS (p < 0.05, hazard ratio 2.43, 95% CI 1.01-5.87). The levels of hemoglobin (11.5 ± 1.7 g/dL vs. 11 ± 1.6 g/dL, p = 0.006) and platelets (208 ± 63 g/L vs. 185 ± 63 g/L, p = 0.002) significantly decreased one month after cycle three, though only two grade 3 anemia and one grade 3 thrombocytopenia were recorded. CONCLUSION: A further intensive PSMA-RLT course is well tolerated in mCRPC patients and associated with promising response rates and OS.

Christian Doppler Laboratory for Applied Metabolomics Medical University of Vienna 1090 Vienna Austria

Department of Urology 2nd Faculty of Medicine Charles University 15006 Prague Czech Republic

Department of Urology Medical University of Vienna 1090 Vienna Austria

Department of Urology University of Texas Southwestern Medical Center Dallas TX 75390 USA

Department of Urology Weill Cornell Medical College New York NY 10065 USA

Division of Nuclear Medicine Department of Biomedical Imaging and Image guided Therapy Medical University of Vienna 1090 Vienna Austria

Institute for Urology and Reproductive Health 1 M Sechenov 1st Moscow State Medical University 119991 Moscow Russia

Ludwig Boltzmann Institute Applied Diagnostics 1090 Vienna Austria

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