PURPOSE: [177Lu]Lu-PSMA-617 radio-ligand therapy (PSMA-RLT) is emerging in patients with an advanced metastatic castration-resistant prostate cancer (mCRPC). Here, we aimed to estimate the results of PSMA-RLT in terms of response, progression-free survival (PFS), and overall survival (OS) in patients receiving a highly standardized treatment regimen due to mCRPC. The toxicity of PSMA-RLT has also been evaluated. PATIENTS AND METHODS: Fifty-four patients (mean age 72 ± 7 years, median PSA at time of initial therapy 66 [range 1.0-4890 μg/L]), receiving three PSMA-RLT cycles (mean 7315 ± 573 MBq) at four weekly intervals, were included in this retrospective analysis. Hematological and biochemical parameters were regularly determined in every patient. Kaplan-Meier estimates were used to assess PFS and OS and a Cox proportional hazard model was used to analyze significant associations. Treatment response was based on PSA measurements 4 weeks after the 3rd treatment. RESULTS: The majority of patients were previously treated with abiraterone/enzalutamide (69%) and docetaxel/cabazitaxel (67%). In total, 79% of the patients showed a decrease in PSA (median PSA decrease from 66 to 19.8, range 0.7-4563 μg/L, P < 0.001) 1 month after the 3rd therapy cycle. Among them, 58% and 35% demonstrated a PSA-decline of > 50% and > 80%, respectively. Median OS was 119 weeks; median PFS was 25 weeks. Patients presenting with a PSA decline had significantly longer PFS (27 vs. 15 weeks, P < 0.0001) and OS (median survival not reached vs. 52 weeks, P < 0.001) than patients with no PSA reduction. Moreover, patients with reduction in PSA levels ≥ 50% (median survival not reached vs. 52 weeks, P < 0.0001) and ≥ 80% (median survival not reached vs. 87 weeks, P = 0.008) lived significantly longer. While hemoglobin did not change during treatment, levels of platelets (236 ± 71 g/L vs. 193 ± 67 g/L) and leucocytes (6.5, range 2.9-13.7 g/L vs. 4.8, range 1.5-12.3 g/L) decreased significantly, both P < 0.001. Two grade 3 leukocytopenia and one grade 3 anemia were observed. CONCLUSION: Intense PSMA-RLT regime with four weekly intervals between the cycles is well-tolerated and offers favorable response rates, PFS, and survival rates for patients with mCRPC.

CBmed GmbH Center for Biomarker Research in Medicine Graz Austria

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

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

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

Department of Urology Comprehensive Cancer Center Vienna General Hospital Medical University of Vienna Vienna Austria

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

Department of Urology Weill Cornell Medical College New York NY USA

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

Ludwig Boltzmann Institute Applied Diagnostics Vienna Austria

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Torre LA, Siegel RL, Ward EM, Jemal A. Global cancer incidence and mortality rates and trends--an update. Cancer Epidemiol Biomark Prev. 2016;25:16–27. doi: 10.1158/1055-9965.EPI-15-0578. PubMed DOI

Jemal A, Siegel R, Xu J, Ward E. Cancer statistics, 2010. CA Cancer J Clin. 2010;60:277–300. doi: 10.3322/caac.20073. PubMed DOI

Wang X, Yin L, Rao P, Stein R, Harsch KM, Lee Z, et al. Targeted treatment of prostate cancer. J Cell Biochem. 2007;102:571–579. doi: 10.1002/jcb.21491. PubMed DOI

Ahmadzadehfar H, Rahbar K, Kurpig S, Bogemann M, Claesener M, Eppard E, et al. Early side effects and first results of radioligand therapy with (177)Lu-DKFZ-617 PSMA of castrate-resistant metastatic prostate cancer: a two-centre study. EJNMMI Res. 2015;5:114. PubMed PMC

Tagawa ST, Milowsky MI, Morris M, Vallabhajosula S, Christos P, Akhtar NH, et al. Phase II study of Lutetium-177-labeled anti-prostate-specific membrane antigen monoclonal antibody J591 for metastatic castration-resistant prostate cancer. Clin Cancer Res. 2013;19:5182–5191. doi: 10.1158/1078-0432.CCR-13-0231. PubMed DOI PMC

McBean R, O'Kane B, Parsons R, Wong D. Lu177-PSMA therapy for men with advanced prostate cancer: Initial 18 months experience at a single Australian tertiary institution. J Med Imaging Radiat Oncol. 2019. PubMed

Rahbar K, Bode A, Weckesser M, Avramovic N, Claesener M, Stegger L, et al. Radioligand Therapy With 177Lu-PSMA-617 as A Novel Therapeutic option in patients with metastatic castration resistant prostate cancer. Clin Nucl Med. 2016;41:522–528. doi: 10.1097/RLU.0000000000001240. PubMed DOI

Kratochwil C, Giesel FL, Stefanova M, Benesova M, Bronzel M, Afshar-Oromieh A, et al. PSMA-targeted radionuclide therapy of metastatic castration-resistant prostate cancer with 177Lu-Labeled PSMA-617. J Nucl Med. 2016;57:1170–1176. doi: 10.2967/jnumed.115.171397. PubMed DOI

Yadav MP, Ballal S, Sahoo RK, Dwivedi SN, Bal C. Radioligand therapy with (177)Lu-PSMA for metastatic castration-resistant prostate cancer: a systematic review and meta-analysis. AJR Am J Roentgenol. 2019:1–11. PubMed

Hofman MS, Violet J, Hicks RJ, Ferdinandus J, Thang SP, Akhurst T, et al. [(177)Lu]-PSMA-617 radionuclide treatment in patients with metastatic castration-resistant prostate cancer (LuPSMA trial): a single-centre, single-arm, phase 2 study. Lancet Oncol. 2018;19:825–833. doi: 10.1016/S1470-2045(18)30198-0. PubMed DOI

Grubmuller B, Senn D, Kramer G, Baltzer P, D'Andrea D, Grubmuller KH, et al. Response assessment using (68)Ga-PSMA ligand PET in patients undergoing (177)Lu-PSMA radioligand therapy for metastatic castration-resistant prostate cancer. Eur J Nucl Med Mol Imaging. 2019;46:1063–1072. doi: 10.1007/s00259-018-4236-4. PubMed DOI PMC

Rahbar Kambiz, Afshar-Oromieh Ali, Jadvar Hossein, Ahmadzadehfar Hojjat. PSMA Theranostics: Current Status and Future Directions. Molecular Imaging. 2018;17:153601211877606. doi: 10.1177/1536012118776068. PubMed DOI PMC

Fendler WP, Reinhardt S, Ilhan H, Delker A, Boning G, Gildehaus FJ, et al. Preliminary experience with dosimetry, response and patient reported outcome after 177Lu-PSMA-617 therapy for metastatic castration-resistant prostate cancer. Oncotarget. 2017;8:3581–3590. doi: 10.18632/oncotarget.12240. PubMed DOI PMC

Ahmadzadehfar H, Eppard E, Kurpig S, Fimmers R, Yordanova A, Schlenkhoff CD, et al. Therapeutic response and side effects of repeated radioligand therapy with 177Lu-PSMA-DKFZ-617 of castrate-resistant metastatic prostate cancer. Oncotarget. 2016;7:12477–12488. doi: 10.18632/oncotarget.7245. PubMed DOI PMC

Ferdinandus J, Eppard E, Gaertner FC, Kurpig S, Fimmers R, Yordanova A, et al. Predictors of response to radioligand therapy of metastatic castrate-resistant prostate cancer with 177Lu-PSMA-617. J Nucl Med. 2017;58:312–319. doi: 10.2967/jnumed.116.178228. PubMed DOI

Rahbar K, Boegemann M, Yordanova A, Eveslage M, Schafers M, Essler M, et al. PSMA targeted radioligandtherapy in metastatic castration resistant prostate cancer after chemotherapy, abiraterone and/or enzalutamide. A retrospective analysis of overall survival. Eur J Nucl Med Mol Imaging. 2018;45:12–19. doi: 10.1007/s00259-017-3848-4. PubMed DOI

Emmett L, Crumbaker M, Ho B, Willowson K, Eu P, Ratnayake L, et al. Results of a Prospective Phase 2 Pilot Trial of (177)Lu-PSMA-617 Therapy for metastatic castration-resistant prostate cancer including imaging predictors of treatment response and patterns of progression. Clin Genitourin Cancer. 2019;17:15–22. doi: 10.1016/j.clgc.2018.09.014. PubMed DOI

Baum RP, Kulkarni HR, Schuchardt C, Singh A, Wirtz M, Wiessalla S, et al. 177Lu-labeled prostate-specific membrane antigen radioligand therapy of metastatic castration-resistant prostate cancer: safety and efficacy. J Nucl Med. 2016;57:1006–1013. doi: 10.2967/jnumed.115.168443. PubMed DOI

Zechmann CM, Afshar-Oromieh A, Armor T, Stubbs JB, Mier W, Hadaschik B, et al. Radiation dosimetry and first therapy results with a (124)I/ (131)I-labeled small molecule (MIP-1095) targeting PSMA for prostate cancer therapy. Eur J Nucl Med Mol Imaging. 2014;41:1280–1292. doi: 10.1007/s00259-014-2713-y. PubMed DOI PMC

Rahbar K, Bogeman M, Yordanova A, Eveslage M, Schafers M, Essler M, et al. Delayed response after repeated (177)Lu-PSMA-617 radioligand therapy in patients with metastatic castration resistant prostate cancer. Eur J Nucl Med Mol Imaging. 2018;45:243–246. doi: 10.1007/s00259-017-3877-z. PubMed DOI

Yadav MP, Ballal S, Tripathi M, Damle NA, Sahoo RK, Seth A, et al. (177)Lu-DKFZ-PSMA-617 therapy in metastatic castration resistant prostate cancer: safety, efficacy, and quality of life assessment. Eur J Nucl Med Mol Imaging. 2017;44:81–91. doi: 10.1007/s00259-016-3481-7. PubMed DOI

Brauer A, Grubert LS, Roll W, Schrader AJ, Schafers M, Bogemann M, et al. (177)Lu-PSMA-617 radioligand therapy and outcome in patients with metastasized castration-resistant prostate cancer. Eur J Nucl Med Mol Imaging. 2017;44:1663–1670. doi: 10.1007/s00259-017-3751-z. PubMed DOI

Rathke H, Giesel FL, Flechsig P, Kopka K, Mier W, Hohenfellner M, et al. Repeated (177)Lu-labeled PSMA-617 radioligand therapy using treatment activities of up to 9.3 GBq. J Nucl Med. 2018;59:459–465. doi: 10.2967/jnumed.117.194209. PubMed DOI

Assessment of PSMA Expression of Healthy Organs in Different Stages of Prostate Cancer Using [68Ga]Ga-PSMA-11-PET Examinations

Response to [ 177 Lu]Lu-PSMA radioligand therapy in metastatic castration-resistant prostate cancer patients presenting with only lymph node metastases

Renal and Salivary Gland Functions after Three Cycles of PSMA-617 Therapy Every Four Weeks in Patients with Metastatic Castration-Resistant Prostate Cancer

Response and Toxicity to the Second Course of 3 Cycles of 177Lu-PSMA Therapy Every 4 Weeks in Patients with Metastatic Castration-Resistant Prostate Cancer

Prediction of response and survival after standardized treatment with 7400 MBq 177Lu-PSMA-617 every 4 weeks in patients with metastatic castration-resistant prostate cancer