Nuclear Medicine and Molecular Imaging

, Volume 53, Issue 6, pp 423–431 | Cite as

Safety Profile and Therapeutic Efficacy of One Cycle of Lu177-PSMA in End-Stage Metastatic Castration-Resistant Prostate Cancer Patients with Low Performance Status

  • Manoj GuptaEmail author
  • Partha Sarathi Choudhury
  • Sudhir Rawal
  • G. Karthikeyan
  • Vineet Talwar
  • Kumar Deep Dutta
  • Amitabh Singh
Original Article



The aim of this study was to evaluate safety and therapeutic efficacy of lutetium 177 prostate-specific membrane antigen (Lu-177-PSMA) in metastatic castration-resistant prostate cancer (mCRPC) patients with low performance status.


Twenty-two patients already treated with anti-androgens and docetaxel were enrolled for one cycle of Lu-177-PSMA therapy. Haemoglobin, total leukocyte counts, platelets and serum creatinine for toxicity profile while prostate specific antigen (PSA), Eastern Cooperative Oncology Group (ECOG) performance status, visual analogue scale (VAS) and analgesic quantification scale (AQS) for therapeutic efficacy were recorded pre and 8 weeks post therapy. Wilcoxon signed-rank and ANOVA tests were used for statistical analysis.


Partial response (PR), stable disease (SD) and progressive disease (PD) for PSA were seen in 5 (22.7%), 13 (59.1%) and 4 (18.2%) patients respectively treated with mean 6.88 GBq dose of Lu-177-PSMA. 8/22 (36.4%) patients showed ≥ 30% drop in PSA. Grade 3 haemoglobin toxicity was seen in 5/22 (22.7%) patients. No patient developed grade 4 haemoglobin toxicity. No patients had grade 3 or 4 leukocytopenia or thrombocytopenia. Wilcoxon signed-rank test showed statistical significant (P < 0.05) difference in pre and post treatment ECOG, VAS, and AQS scores. The ANOVA test showed statistically significant difference in mean doses of Lu-177-PSMA used in three PSA response groups while difference was non-significant for other variables.


We concluded that Lu-177-PSMA therapy has adequate pain palliation in end-stage mCRPC patients with low performance status and it has a potential to become effective therapeutic option in properly selected patients.


Lu-177-PSMA Safety and efficacy Metastatic castration resistant prostate cancer Low performance status 


Compliance with Ethical Standards

Conflict of Interest

Manoj Gupta, Partha Sarathi Choudhury, Sudhir Rawal, G. Karthikeyan, Vineet Talwar, Kumar Deep Dutta and Amitabh Singh declare that they have no conflict of interest.

Ethical Statement

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed Consent

The institutional review board waived the need to obtain informed consent for this retrospective study.

Supplementary material

13139_2019_624_MOESM1_ESM.docx (14 kb)
Supplementary Table 1 (DOCX 13 kb)


  1. 1.
    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.CrossRefGoogle Scholar
  2. 2.
    Jain S, Saxena S, Kumar A. Epidemiology of prostate cancer in India. Meta Gene. 2014;2:596–605.CrossRefGoogle Scholar
  3. 3.
    Jemal A, Siegel R, Xu J, Ward E. Cancer statistics, 2010. CA Cancer J Clin. 2010;60:277–300.CrossRefGoogle Scholar
  4. 4.
    Ryan CJ, Smith MR, Fizazi K, Saad F, Mulders PF, Sternberg CN, et al. Abiraterone acetate plus prednisone versus placebo plus prednisone in chemotherapy-naive men with metastatic castration-resistant prostate cancer (COU-AA-302): final overall survival analysis of a randomised, double-blind, placebo-controlled phase 3 study. Lancet Oncol. 2015;16:152–60.CrossRefGoogle Scholar
  5. 5.
    Scher HI, Fizazi K, Saad F, Taplin ME, Sternberg CN, Miller K, et al. Increased survival with enzalutamide in prostate cancer after chemotherapy. N Engl J Med. 2012;367:1187–97.CrossRefGoogle Scholar
  6. 6.
    de Bono JS, Oudard S, Ozguroglu M, Hansen S, Machiels JP, Kocak I, et al. Prednisone plus cabazitaxel or mitoxantrone for metastatic castration-resistant prostate cancer progressing after docetaxel treatment: a randomised open-label trial. Lancet. 2010;376:1147–54.CrossRefGoogle Scholar
  7. 7.
    Parker C, Nilsson S, Heinrich D, Helle SI, O'Sullivan JM, Fosså SD, et al. Alpha emitter radium-223 and survival in metastatic prostate cancer. N Engl J Med. 2013;369:213–23.CrossRefGoogle Scholar
  8. 8.
    Benešová M, Schäfer M, Bauder-Wüst U, Afshar-Oromieh A, Kratochwil C, Mier W, et al. Preclinical evaluation of a tailor-made DOTA-conjugated PSMA inhibitor with optimized linker moiety for imaging and endoradiotherapy of prostate cancer. J Nucl Med. 2015;56:914–20.CrossRefGoogle Scholar
  9. 9.
    Kratochwil C, Giesel FL, Stefanova M, Benešová 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;57:1170–6.CrossRefGoogle Scholar
  10. 10.
    Silver DA, Pellicer I, Fair WR, Heston WD, Cordon-Cardo C. Prostate-specific membrane antigen expression in normal and malignant human tissues. Clin Cancer Res. 1997;3:81–5.PubMedGoogle Scholar
  11. 11.
    Sweat SD, Pacelli A, Murphy GP, Bostwick DG. Prostate-specific membrane antigen expression is greatest in prostate adenocarcinoma and lymph node metastases. Urology. 1998;52:637–40.CrossRefGoogle Scholar
  12. 12.
    Green S, Weiss GR. Southwest Oncology Group standard response criteria, endpoint definitions and toxicity criteria. Investig New Drugs. 1992;10:239–53.CrossRefGoogle Scholar
  13. 13.
    Scher HI, Morris MJ, Stadler WM, et al. Trial design and objectives for castration-resistant prostate cancer: updated recommendations from the prostate cancer clinical trials working group 3. J Clin Oncol. 2016;34:1402–18.CrossRefGoogle Scholar
  14. 14.
    Oken MM, Creech RH, Tormey DC, Horton J, Davis TE, McFadden ET, et al. Toxicity and response criteria of the Eastern Cooperative Oncology Group. Am J Clin Oncol. 1982;5:649–55.CrossRefGoogle Scholar
  15. 15.
    Basch E, Trentacosti AM, Burke LB, Kwitkowski V, Kane RC, Autio KA, et al. Pain palliation measurement in cancer clinical trials: the US Food and Drug Administration perspective. Cancer. 2014;120:761–7.CrossRefGoogle Scholar
  16. 16.
    Jadvar H. Molecular imaging of prostate cancer: PET radiotracers. AJR Am J Roentgenol. 2012;199:278–91.CrossRefGoogle Scholar
  17. 17.
    Virgolini I, Decristoforo C, Haug A, Fanti S, Uprimny C. Current status of theranostics in prostate cancer. Eur J Nucl Med Mol Imaging. 2018;45:471–95.CrossRefGoogle Scholar
  18. 18.
    Mease RC, Foss CA, Pomper MG. PET imaging in prostate cancer: focus on prostate specific membrane antigen. Curr Top Med Chem. 2013;13:951–62.CrossRefGoogle Scholar
  19. 19.
    Barinka C, Rojas C, Slusher B, Pomper M. Glutamate carboxypeptidase II in diagnosis and treatment of neurologic disorders and prostate cancer. Curr Med Chem. 2012;19:856–70.CrossRefGoogle Scholar
  20. 20.
    Yao V, Parwani A, Maier C, Heston WD, Bacich DJ. Moderate expression of prostate-specific membrane antigen, a tissue differentiation antigen and folate hydrolase, facilitates prostate carcinogenesis. Cancer Res. 2008;68:9070–7.CrossRefGoogle Scholar
  21. 21.
    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;19:5182–91.CrossRefGoogle Scholar
  22. 22.
    Afshar-Oromieh A, Malcher A, Eder M, Eisenhut M, Linhart HG, Hadaschik BA, et al. PET imaging with a [68Ga]gallium-labelled PSMA ligand for the diagnosis of prostate cancer: biodistribution in humans and first evaluation of tumour lesions. Eur J Nucl Med Mol Imaging. 2013;40:486–95.CrossRefGoogle Scholar
  23. 23.
    Han S, Woo S, Kim YJ, Suh CH. Impact of 68Ga-PSMA PET on the management of patients with prostate cancer: a systematic review and meta-analysis. Eur Urol. 2018;74:179–90.CrossRefGoogle Scholar
  24. 24.
    Kabasakal L, AbuQbeitah M, Aygün A, Yeyin N, Ocak M, Demirci E, et al. Pre-therapeutic dosimetry of normal organs and tissues of (177)Lu-PSMA-617 prostate-specific membrane antigen (PSMA) inhibitor in patients with castration-resistant prostate cancer. Eur J Nucl Med Mol Imaging. 2015;42:1976–83.CrossRefGoogle Scholar
  25. 25.
    Delker A, Fendler WP, Kratochwil C, Brunegraf A, Gosewisch A, Gildehaus FJ, et al. Dosimetry for 177Lu-DKFZ-PSMA-617: a new radiopharmaceutical for the treatment of metastatic prostate cancer. Eur J Nucl Med Mol Imaging. 2016;43:42–51.CrossRefGoogle Scholar
  26. 26.
    Ahmadzadehfar H, Rahbar K, Kürpig S, Bögemann 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.PubMedGoogle Scholar
  27. 27.
    Rahbar K, Schmidt M, Heinzel A, Eppard E, Bode A, Yordanova A, et al. Response and tolerability of a single dose of 177Lu-PSMA-617 in patients with metastatic castration-resistant prostate cancer: a multicenter retrospective analysis. J Nucl Med. 2016;57:1334–8.CrossRefGoogle Scholar
  28. 28.
    Rahbar K, Ahmadzadehfar H, Kratochwil C, Haberkorn U, Schafers M, Essler M, et al. German multicenter study investigating 177Lu-PSMA-617 radioligand therapy in advanced prostate cancer patients. J Nucl Med. 2017;58:85–90.CrossRefGoogle Scholar
  29. 29.
    Calopedos RJS, Chalasani V, Asher R, Emmett L, Woo HH. Lutetium-177-labelled anti-prostate-specific membrane antigen antibody and ligands for the treatment of metastatic castrate-resistant prostate cancer: a systematic review and meta-analysis. Prostate Cancer Prostatic Dis. 2017;20:352–60.CrossRefGoogle Scholar
  30. 30.
    Hofman MS, Violet J, Hicks RJ, Ferdinandus J, Thang SP, Akhurst T, et al. [177Lu]-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;19:825–33.CrossRefGoogle Scholar
  31. 31.
    Meller B, Bremmer F, Sahlmann C, Hijazi S, Bouter C, Trojan L, et al. Alterations in androgen deprivation enhanced prostate-specific membrane antigen (PSMA) expression in prostate cancer cells as a target for diagnostics and therapy. EJNMMI Res. 2015;5:66.CrossRefGoogle Scholar
  32. 32.
    Murga JD, Moorji SM, Han AQ, Magargal WW, DiPippo VA, Olson WC. Synergistic co-targeting of prostate-specific membrane antigen and androgen receptor in prostate cancer. Prostate. 2015;75:242–54.CrossRefGoogle Scholar
  33. 33.
    Vallabhajosula S, Jhanwar Y, Tagawa S, Epstein J, Babich J, Youn T, et al. 99mTc-MIP-1404 Planar and SPECT scan: Imaging biomarker of androgen receptor (AR) signaling and prostate specific membrane antigen (PSMA) expression. J Nucl Med. 2016;57(supplement 2):1541.Google Scholar

Copyright information

© Korean Society of Nuclear Medicine 2019

Authors and Affiliations

  1. 1.Department of Nuclear MedicineRajiv Gandhi Cancer Institute and Research CentreDelhiIndia
  2. 2.Department of Uro - Gynae Surgical OncologyRajiv Gandhi Cancer Institute and Research CentreDelhiIndia
  3. 3.Amity Institute of Virology and ImmunologyAmity UniversityNoidaIndia
  4. 4.Department of Medical OncologyRajiv Gandhi Cancer Institute and Research CentreDelhiIndia

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