Evaluating the response and side effects of [177Lu]Lu-PSMA therapy in mCRPC patients: A single-center experience from Iran

Document Type : Original Article

Authors

1 Kidney Transplantation research center, Mashhad University of Medical Sciences, Mashhad, Iran

2 Department of Nuclear Medicine, School of Medicine, Iran University of Medical Sciences, Tehran, Iran

3 Nuclear Medicine Research Center, Mashhad University of Medical Sciences, Mashhad, Iran

4 Department of Nuclear Medicine, Rasoul Akram Hospital, Iran University of Medical Sciences, Tehran, Iran

5 Nanotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran

10.22034/irjnm.2025.130185.1700

Abstract

Introduction: To evaluate clinical and laboratory findings in patients undergoing [177Lu]Lu-PSMA treatment for metastatic castration-resistant prostate cancer (mCRPC).
Methods: This cross-sectional study included mCRPC patients treated with [177Lu]Lu-PSMA. Patients underwent regular evaluations by a nuclear medicine specialist, with laboratory tests (CBC, serum PSA, creatinine, and liver functions) conducted before each treatment cycle and at 1-, 4-, and 8-weeks post-treatment. Treatment cycles were repeated every 8-10 weeks to assess response and side effects. Patients received [177Lu]Lu-PSMA intravenously, followed by a 6-hour monitoring period. A pre-designed checklist was used to collect demographic data, clinical manifestations (pain assessment via VAS), treatment complications, and laboratory parameters. The relationships among PSA level changes, age, and radiopharmaceutical dosage were analyzed, along with side effects related to blood cell counts and serum creatinine levels.
Results: This study evaluated the efficacy and safety of [177Lu]Lu-PSMA treatment in 133 metastatic castration-resistant prostate cancer (mCRPC) patients. PSA level decreases in 122 patients (92%), with 39 (29%) achieving a ≥50% reduction. Disease stabilization occurred in 79 patients (59%), while 34 patients (26%) experienced disease progression. Bone pain relief in 41% of 72 patients complaining of baseline pain. Hematological toxicity was observed mostly as grade 1 (67%) and as grade 2 (34%) of the patients. No renal or hepatic complications were observed.
Conclusion: The results suggest that [177Lu]Lu-PSMA treatment is effective in managing metastatic castration-resistant prostate cancer, with a favorable therapeutic response and limited side effects.

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  1. Ferlay J, Colombet M, Soerjomataram I, Parkin DM, Piñeros M, Znaor A, Bray F. Cancer statistics for the year 2020: An overview. Int J Cancer. 2021 Apr 5.
  2. Culp MB, Soerjomataram I, Efstathiou JA, Bray F, Jemal A. Recent global patterns in prostate cancer incidence and mortality rates. Eur Urol. 2020 Jan;77(1):38-52.
  3. Nindra U, Lin P, Becker T, Roberts TL, Chua W. Current state of theranostics in metastatic castrate-resistant prostate cancer. J Med Imaging Radiat Oncol. 2024 Jun;68(4):412-20.
  4. El Fakiri M, Geis NM, Ayada N, Eder M, Eder AC. PSMA-targeting radiopharmaceuticals for prostate cancer therapy: recent developments and future perspectives. Cancers (Basel). 2021 Aug 5;13(16):3967.
  5. Zhang H, Koumna S, Pouliot F, Beauregard JM, Kolinsky M. PSMA theranostics: current landscape and future outlook. Cancers (Basel). 2021 Aug 10;13(16):4023.
  6. Kaittanis C, Andreou C, Hieronymus H, Mao N, Foss CA, Eiber M, Weirich G, Panchal P, Gopalan A, Zurita J, Achilefu S, Chiosis G, Ponomarev V, Schwaiger M, Carver BS, Pomper MG, Grimm J. Prostate-specific membrane antigen cleavage of vitamin B9 stimulates oncogenic signaling through metabotropic glutamate receptors. J Exp Med. 2018 Jan 2;215(1):159-75.
  7. Sokoloff RL, Norton KC, Gasior CL, Marker KM, Grauer LS. A dual-monoclonal sandwich assay for prostate-specific membrane antigen: levels in tissues, seminal fluid and urine. Prostate. 2000 May 1;43(2):150-7.
  8. Emmett L, Willowson K, Violet J, Shin J, Blanksby A, Lee J. Lutetium 177 PSMA radionuclide therapy for men with prostate cancer: a review of the current literature and discussion of practical aspects of therapy. J Med Radiat Sci. 2017 Mar;64(1):52-60.
  9. Dai YH, Chen PH, Lee DJ, Andrade G, Vallis KA. A Meta-Analysis and meta-regression of the efficacy, toxicity, and quality of life outcomes following prostate-specific membrane antigen radioligand therapy utilising lutetium-177 and actinium-225 in metastatic prostate cancer. Eur Urol. 2025 Apr;87(4):398-408.
  10. Groener D, Nguyen CT, Baumgarten J, Bockisch B, Davis K, Happel C, Mader N, Nguyen Ngoc C, Wichert J, Banek S, Mandel P, Chun FKH, Tselis N, Grünwald F, Sabet A. Hematologic safety of 177Lu-PSMA-617 radioligand therapy in patients with metastatic castration-resistant prostate cancer. EJNMMI Res. 2021 Jul 3;11(1):61.
  11. Sartor O, de Bono J, Chi KN, Fizazi K, Herrmann K, Rahbar K, Tagawa ST, Nordquist LT, Vaishampayan N, El-Haddad G, Park CH, Beer TM, Armour A, Pérez-Contreras WJ, DeSilvio M, Kpamegan E, Gericke G, Messmann RA, Morris MJ, Krause BJ; VISION Investigators. Lutetium-177-PSMA-617 for metastatic castration-resistant prostate cancer. N Engl J Med. 2021 Sep 16;385(12):1091-103.
  12. Seifert KE, Seifert R, Kessel K, Roll W, Schlack K, Boegemann M, Rahbar K. Lutetium-177 labelled PSMA targeted therapy in advanced prostate cancer: current status and future perspectives. Cancers (Basel). 2021 Jul 23;13(15):3715.
  13. Vogelzang NJ, Coleman RE, Michalski JM, Nilsson S, O'Sullivan JM, Parker C, Widmark A, Thuresson M, Xu L, Germino J, Sartor O. Hematologic safety of radium-223 dichloride: baseline prognostic factors associated with myelosuppression in the ALSYMPCA trial. Clin Genitourin Cancer. 2017 Feb;15(1):42-52.e8.
  14. Gupta M, Choudhury PS, Rawal S, Karthikeyan G, Talwar V, Dutta KD, Singh A. Safety profile and therapeutic efficacy of one cycle of Lu177-PSMA in end-stage metastatic castration-resistant prostate cancer patients with low performance status. Nucl Med Mol Imaging. 2019 Dec;53(6):423-31.
  15. Ferdinandus J, Eppard E, Gaertner FC, Kürpig S, Fimmers R, Yordanova A, Hauser S, Feldmann G, Essler M, Ahmadzadehfar H. Predictors of response to radioligand therapy of metastatic castrate-resistant prostate cancer with 177Lu-PSMA-617. J Nucl Med. February 2017, 58 (2) 312-319.
  16. Ahmadzadehfar H, Rahbar K, Kürpig S, Bögemann M, Claesener M, Eppard E, Gärtner F, Rogenhofer S, Schäfers M, Essler M. 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 Dec;5(1):114.
  17. Yadav MP, Ballal S, Sahoo RK, Tripathi M, Damle NA, Shamim SA, Kumar R, Seth A, Bal C. Long-term outcome of 177Lu-PSMA-617 radioligand therapy in heavily pre-treated metastatic castration-resistant prostate cancer patients. PLoS One. 2021 May 10;16(5):e0251375.
  18. Patell K, Kurian M, Garcia JA, Mendiratta P, Barata PC, Jia AY, Spratt DE, Brown JR. Lutetium-177 PSMA for the treatment of metastatic castrate resistant prostate cancer: a systematic review. Expert Rev Anticancer Ther. 2023 Jul;23(7):731-44.
  19. von Eyben FE, Bauman G, von Eyben R, Rahbar K, Soydal C, Haug AR, Virgolini I, Kulkarni H, Baum R, Paganelli G. Optimizing PSMA radioligand therapy for patients with metastatic castration-resistant prostate cancer. a systematic review and meta-analysis. Int J Mol Sci. 2020 Nov 28;21(23):9054.
  20. Hofman MS, Emmett L, Sandhu S, Iravani A, Buteau JP, Joshua AM, Goh JC, Pattison DA, Tan TH, Kirkwood ID, Ng S, Francis RJ, Gedye C, Rutherford NK, Weickhardt A, Scott AM, Lee ST, Kwan EM, Azad AA, Ramdave S, Redfern AD, Macdonald W, Guminski A, Hsiao E, Chua W, Lin P, Zhang AY, Stockler MR, Williams SG, Martin AJ, Davis ID; TheraP Trial Investigators and the Australian and New Zealand Urogenital and Prostate Cancer Trials Group. Overall survival with [177Lu]Lu-PSMA-617 versus cabazitaxel in metastatic castration-resistant prostate cancer (TheraP): secondary outcomes of a randomised, open-label, phase 2 trial. Lancet Oncol. 2024 Jan;25(1):99-107.