Therapeutic Outcomes of 177Lu-PSMA Targeted Therapy in Patients with Metastatic Castration-Resistant Prostate Cancer: A Single-Center Study

Document Type : Original Article

Authors

1 Research Center for Nuclear Medicine, Dr. Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran

2 Valiasr Hospital, Tehran University of Medical Sciences

3 Department of Nuclear Medicine, Vali-Asr Hospital Tehran University of Medical Sciences, Tehran 1419731351, Iran

Abstract

Objective(s): This study aimed to evaluate the therapeutic outcomes of 177Lutetium (177Lu)-PSMA-617 in metastatic castrate-resistant prostate cancer (mCRPC) patients, based on post-treatment imaging findings.
Methods: All post-therapeutic scans were collected retrospectively from patients treated with 100-200 mCi 177Lu-PSMA-617 from March 2018 to December 2020 for mCRPC. Two independent readers interpreted the scans and visually categorized them into three strata: responsive, stable, and progressive. The responses were defined based on changes in the number of detected lesions, as well as the intensity of the hottest lesion. Data were registered, and the trend of changes was descriptively discussed.
Results: Out of 36 patients (aged 67±8.8 years), 23 underwent at least two treatment cycles. Nineteen patients (82.6%) had bone metastases, 12 (52.2%) had nodal metastases, 5 (21.7%) had liver metastases, and 3 (13.0%) had lung metastases. Eleven patients (47.8%) were considered responsive in the post-therapeutic scans, two of which experienced complete eradication of the metastatic sites.  Three patients (13%) were categorized as progressive, and 9 (39.1%) patients remained stable. Regarding mortality, nine patients died during the late follow-up (median of 24 months). In the surviving population, 65% reported no or mild pain in the final follow-up, based on a 5-point scale pain assessment.
Conclusion: The treatment of mCRPC patients with 177Lu-PSMA-617 may limit their disease progression and preserve their physical performance, which are important factors in their survival and quality of life.

Keywords

Main Subjects


  1. Torre LA, Siegel RL, Ward EM, Jemal A. Global Cancer Incidence and Mortality Rates and Trends- an UpdateGlobal Cancer Rates and Trends- an Update. Cancer epidemiology, biomarkers & prevention. 2016; 25(1):16-27.
  1. Goldsmith SJ. Targeted radionuclide therapy: a historical and personal review. In Seminars in Nuclear Medicine. 2020; 50(1); 87-97.
  2. 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. Nuclear medicine and molecular imaging. 2019; 53(6):423-31.
  3. 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. Journal of medical radiation sciences. 2017; 64(1):52-60.
  4. Mayor N, Sathianathen NJ, Buteau J, Koschel S, Antón Juanilla M, Kapoor J, Azad A, Hofman MS, Murphy DG. Prostate‐specific membrane antigen theranostics in advanced prostate cancer: an evolving BJU international. 2020; 126(5): 525-35.
  5. Hofman MS, Violet J, Hicks RJ, Ferdinandus J, Thang SP, Akhurst T, Iravani A, Kong G, Kumar AR, Murphy DG, Eu P. [177Lu]-PSMA-617 radionuclide treatment in patients with metastatic castration-resistant prostate cancer (LuPSMA trial): a single-centre, single-arm, phase 2 study. The Lancet Oncology. 2018; 19(6):825-33.
  6. Keam SJ. Lutetium Lu 177 Vipivotide Tetraxetan: First Approval. Molecular diagnosis & therapy. 2022; 13:1-9.
  7. Assadi M, Rezaei S, Jafari E, Rekabpour SJ, Ravanbod M, Zohrabi F, Amini A, Keshmiri S, Dadgar H, Ahmadzadehfar H. Potential application of lutetium-177-labeled prostate-specific membrane antigen-617 radioligand therapy for metastatic castration-resistant prostate cancer in a limited resource environment: Initial clinical experience after 2 years. World Journal of Nuclear Medicine. 2020; 19(01): 15-20.
  8. Aghdam RA, Amoui M, Ghodsirad M, Khoshbakht S, Mofid B, Kaghazchi F, Tavakoli M, Pirayesh E, Ahmadzadehfar H. Efficacy and safety of 177Lutetium-prostate-specific membrane antigen therapy in metastatic castration-resistant prostate cancer patients: First experience in West Asia–A prospective study. World journal of nuclear medicine. 2019; 18(03): 258-65.
  9. Moghadam SZ, Askari E, Divband G, Shakeri S, Aryana K. Efficacy, safety and prognostic factors affecting overall survival among metastatic prostate cancer patients undergoing treatment with 177Lu-PSMA-617: a single center study. Revista Española de Medicina Nuclear e Imagen Molecular (English Edition). 2021 Sep 12.
  10. Kratochwil C, Fendler WP, Eiber M, Baum R, Bozkurt MF, Czernin J, Delgado Bolton RC, Ezziddin S, Forrer F, Hicks RJ, Hope TA. EANM procedure guidelines for radionuclide therapy with 177Lu-labelled PSMA-ligands (177Lu-PSMA-RLT). European journal of nuclear medicine and molecular imaging. 2019; 46(12):2536-44.
  11. Sathekge M, Bruchertseifer F, Knoesen O, Reyneke F, Lawal I, Lengana T, Davis C, Mahapane J, Corbett C, Vorster M, Morgenstern A. 225Ac-PSMA-617 in chemo-therapy-naive patients with advanced prostate cancer: a pilot study. European journal of nuclear medicine and molecular imaging. 2019; 46(1):129-38.
  12. Lenzo NP, Meyrick D, Turner JH. Review of gallium-68 PSMA PET/CT imaging in the management of prostate cancer. Diagnostics. 2018; 8(1):16.
  13. Fendler WP, Rahbar K, Herrmann K, Kratochwil C, Eiber M. 177Lu-PSMA radioligand therapy for prostate cancer. Journal of Nuclear Medicine. 2017; 58(8): 1196-200.
  14. Banerjee S, Pillai MR, Knapp FF. Lutetium-177 therapeutic radiopharmaceuticals: linking chemistry, radiochemistry, and practical applications. Chemical reviews. 2015 Apr 22; 115(8):2934-74.
  15. Mahmoudi E, Pirayesh E, Deevband MR, Amoui M, Rad MG, Rad MG, Ghorbani M. Radiation Dose to Medical Staff in 177Lu-PSMA-DKFZ-617 therapy And Estimation of Annual Dose. Journal of Nuclear Medicine Technology. 2022;50(3):269-273
  16. Heck MM, Tauber R, Schwaiger S, Retz M, D’Alessandria C, Maurer T, Gafita A, Wester HJ, Gschwend JE, Weber WA, Schwaiger M. Treatment outcome, toxicity, and predictive factors for radioligand therapy with 177Lu-PSMA-I&T in metastatic castration-resistant prostate cancer. European urology. 2019; 75(6):920-6.
  17. Rahbar K, Ahmadzadehfar H, Kratochwil C, Haberkorn U, Schäfers M, Essler M, Baum RP, Kulkarni HR, Schmidt M, Drzezga A, Bartenstein P. German multicenter study investigating 177Lu-PSMA-617 radioligand therapy in advanced prostate cancer patients. Journal of Nuclear Medicine. 2017; 58(1):85-90.
  18. Yadav MP, Ballal S, Bal C, Sahoo RK, Damle NA, Tripathi M, Seth A. Efficacy and safety of 177Lu-PSMA-617 radioligand therapy in metastatic castration-resistant prostate cancer patients. Clinical nuclear medicine. 2020 Jan 1; 45(1):19-31.
  19. Kim YJ, Kim YI. Therapeutic responses and survival effects of 177Lu-PSMA-617 radioligand therapy in metastatic castrate-resistant prostate cancer: a meta-analysis. Clinical nuclear medicine. 2018; 43(10): 728-34.
  20. Morris MJ, De Bono JS, Chi KN, Fizazi K, Herrmann K, Rahbar K, Tagawa ST, Nordquist LT, Vaishampayan N, El-Haddad G, Park CH. Phase III study of lutetium-177-PSMA-617 in patients with metastatic castration-resistant prostate cancer (VISION). Journal of Clinical Oncology. 2021; 39(18) sup l.
  21. Fanti S, Goffin K, Hadaschik BA, Herrmann K, Maurer T, MacLennan S, Oprea-Lager DE, Oyen WJ, Rouvière O, Mottet N, Bjartell A. Consensus statements on PSMA PET/CT response assessment criteria in prostate cancer. European Journal of Nuclear Medicine and Molecular Imaging. 2021; 48(2):469-76.
  22. Fanti S, Hadaschik B, Herrmann K. Proposal for systemic-therapy response-assessment criteria at the time of PSMA PET/CT imaging: the PSMA PET progression criteria. Journal of Nuclear Medicine. 2020; 61(5):678-82.
  23. Gafita A, Rauscher I, Weber M, Hadaschik B, Wang H, Armstrong WR, Tauber R, Grogan TR, Czernin J, Rettig MB, Herrmann K. Novel framework for treatment response evaluation using PSMA-PET/CT in patients with metastatic castration-resistant prostate cancer (RECIP 1.0): an inter-national multicenter study. Journal of Nuclear Medicine. 2022; 63(11):1651-1658.
  24. Hussain M, Goldman B, Tangen C, Higano CS, Petrylak DP, Wilding G, Akdas AM, Small EJ, Donnelly BJ, Sundram SK, Burch PA. Prostate-specific antigen progression predicts overall survival in patients with metastatic prostate cancer: data from Southwest Oncology Group Trials 9346 (Intergroup Study 0162) and 9916. Journal of clinical oncology. 2009; 27(15):2450.