Skip to main content
SpringerLink
Log in

Targeted Radionuclide Therapy and Immunotherapy of Metastatic Prostate Cancer

  • Chapter
  • First Online:
Nuclear Medicine and Immunology

  • 1274 Accesses

Abstract

Metastatic prostate cancer is not curable. There have been major strides in the treatment of patients with castration-resistant prostate cancer with many available therapeutic options which generally prolong the overall survival about an average of 4 months. The more recent advances are in immunotherapy and targeted radionuclide therapy, which are the focus of this chapter. We review the current evidence in these arenas and comment on future developments that are anticipated to transform the treatment landscape of patients with metastatic prostate cancer.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 159.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. National Cancer Institute Surveillance, Epidemiology, and End Results Program. https://seer.cancer.gov/statfacts/html/prost.html. Accessed 31 Dec 2019.

  2. Mohler JL, Antonarakis ES, Armstrong AJ, et al. NCCN clinical practice guidelines in oncology: prostate cancer, version 2.2019. J Natl Compr Cancer Netw. 2019;17:479–505.

    Article  CAS  Google Scholar 

  3. Iagaru AH, Mittra E, Colletti PM, Jadvar H. Bone-targeted imaging and radionuclide therapy in prostate cancer. J Nucl Med. 2016;57:19S–24S.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Parker C, Nilsson S, Heinrich D, et al. Alpha emitter radium-223 and survival in metastatic prostate cancer. N Engl J Med. 2013;369:213–23.

    Article  CAS  PubMed  Google Scholar 

  5. Dizdarevic S, Petersen PM, Essler M, et al. Interim analysis of the REASSURE (Radium-223 alpha emitter agent in non-intervention safety study in mCRPC popUlation for long-teRm Evaluation) study: patient characteristics and safety according to prior use of chemotherapy in routine clinical practice. Eur J Nucl Med Mol Imaging. 2019;46:1102–10.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Dizdarevic S, McCready R, Vinjamuri S. Radium-223 dichloride in prostate cancer: proof of principle for the use of targeted alpha treatment in clinical practice. Eur J Nucl Med Mol Imaging. 2020;47:192–217.

    Article  CAS  PubMed  Google Scholar 

  7. Etchebehere EC, Milton DR, Araujo JC, et al. Factors affecting 223Ra therapy: clinical experience after 532 cycles from a single institution. Eur J Nucl Med Mol Imaging. 2016;43:8–20.

    Article  CAS  PubMed  Google Scholar 

  8. Jadvar H, Quinn DI, Conti PS. One-year postapproval clinical experience with radium-223 dichloride in patients with metastatic castrate-resistant prostate cancer. Cancer Biother Radiopharm. 2015;30:195–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Castello A, Macapinlac H, Lopci E, Santos EB. Prostate-specific antigen flare induced by 223RaCl2 in patients with metastatic castration-resistant prostate cancer. Eur J Nucl Med Mol Imaging. 2018;45:2256–63.

    Article  CAS  PubMed  Google Scholar 

  10. Sartor O, Heinrich D, Mariados N, et al. Re-treatment with radium-223: first experience from an international, open-label, phase I/11 study in patients with castration-resistant prostate cancer and bone metastases. Ann Oncol. 2017;28:2464–71.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Morris MJ, Loriot Y, Sweeney CJ, et al. Radium-223 in combination with docetaxel in patients with castration-resistant prostate cancer and bone metastases: a phase 1 escalation/randomized phase 2a trial. Eur J Cancer. 2019;114:107–16. [Epub ahead of print].

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Jadvar H, Chen X, Cai W, Mahmood U. Radiotheranostics in cancer diagnosis and management. Radiology. 2018;286:388–400.

    Article  PubMed  Google Scholar 

  13. Bouchelouche K, Tagawa ST, Goldsmithe SJ, et al. PET/CT imaging and radioimmunotherapy of prostate cancer. Semin Nucl Med. 2011;41:29–44.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Osmany S, Zaheer S, Bartel T, et al. Gallium-68-labeled prostate-specific membrane antigen-11 PET/CT of prostate and nonprostate cancers. AJR Am J Roentgenol. 2019;213:286–99.

    Article  PubMed  PubMed Central  Google Scholar 

  15. Rahbar K, Afshar-Oromieh A, Jadvar H, Ahmadzadefar H. PSMA theranostics: current status and future directions. Mol Imaging. 2018;17 https://doi.org/10.1177/1536012118776068.

  16. Ahmadzadehfar H, Rahbar K, Kurpig S, 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 center study. EJNMMI Res. 2015;5(1):114.

    Article  PubMed  Google Scholar 

  17. Ahmadzadehfar H, Eppard E, Kurpig S, 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(11):12477–88.

    Article  PubMed  PubMed Central  Google Scholar 

  18. Ahmadzadehfar H, Wegen S, Yordanova A, et al. Overall survival and response pattern of castration-resistant metastatic prostate cancer to multiple cycles of radioligand therapy using [177Lu]Lu-PSMA-617. Eur J Nucl Med Mol Imaging. 2017;44(9):1448–54.

    Article  CAS  PubMed  Google Scholar 

  19. Rahbar K, Bogeman M, Yordanova A, 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(2):243–6.

    Article  CAS  PubMed  Google Scholar 

  20. Ahmadzadehfar H, Zimbelmann S, Yordanova A, et al. Radioligand therapy of metastatic prostate cancer using 177Lu-PSMA-617 after radiation exposure to 223Ra-dichloride. Oncotarget. 2017;8(33):55567–74.

    Article  PubMed  PubMed Central  Google Scholar 

  21. Rahbar K, Bode A, Weckesser M, 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(7):522–8.

    Article  PubMed  Google Scholar 

  22. Rahbar K, Schmidt M, Heinzel 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(9):1334–8.

    Article  CAS  PubMed  Google Scholar 

  23. Rahbar K, Ahmadzadehfar H, Kratochwil C, et al. German multicenter study investigating 177Lu-PSMA-617 radioligand therapy in advanced prostate cancer patients. J Nucl Med. 2017;58(1):85–90.

    Article  CAS  PubMed  Google Scholar 

  24. Rahbar K, Boegemann M, Yordanova A, et al. PSMA targeted radioligand therapy 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(1):12–9.

    Article  CAS  PubMed  Google Scholar 

  25. Kratochwil C, Giesel FL, Stefanova M, et al. PSMA-targeted radionuclide therapy of metastatic castration-resistant prostate cancer with 177Lu-labeled PSMA-617. J Nucl Med. 2016;57:1170–6.

    Article  CAS  PubMed  Google Scholar 

  26. Baum RP, Kulkarni HR, Schuchardt C, et al. 177Lu-labeled prostate-specific membrane antigen radioligand therapy of metastatic castration-resistant prostate cancer: safety and efficacy. J Nucl Med. 2015;7:1006–13.

    Google Scholar 

  27. Kulkarni HR, Singh A, Schuchardt C, et al. PSMA-based radioligand therapy for metastatic castration-resistant prostate cancer: the Bad Berka experience since 2013. J Nucl Med. 2016;57:97S–104S.

    Article  CAS  PubMed  Google Scholar 

  28. Yadav MP, Ballal S, Sahoo RK, et al. Radioligand therapy with 177Lu-PSMA for metastatic castration-resistant prostate cancer: a systematic review and meta-analysis. AJR Am J Roentgenol. 2019;213:275–85.

    Article  PubMed  Google Scholar 

  29. Kratochwil C, Fendler WP, Eiber M, et al. EANM procedure guidelines for radionuclide therapy with 177Lu-labelled PSMA-ligands (177Lu-PSMA-RLT). Eur J Nucl Med Mol Imaging. 2019;46:2536–44.

    Article  PubMed  Google Scholar 

  30. Rahbar K, Bodei L, Morris MJ. Is the vision of radioligand therapy for prostate cancer becoming a reality? An overview of the phase III VISION trial and its importance for the future of theranostics. J Nucl Med. 2019;60:1504–6.

    Article  CAS  PubMed  Google Scholar 

  31. Hofman MS, Violet J, Hicks RJ, et al. [177Lu]-PSMA-617 radioligand therapy in patients with metastatic castration-resistant prostate cancer (LuPSMA trial): a single-center, single-arm, phase 2 study. Lancet Oncol. 2018;19:825–33.

    Article  CAS  PubMed  Google Scholar 

  32. Emmett L, Crumbaker M, Ho B, et al. Results of a prospective phase 2 pilot trial of 177Lu-PSMA-617 therapy for metastatic castration-resistant prostate Cancer including imaging predictors of treatment response and patterns of progression. Clin Genitourin Cancer. 2019;17(1):15–22.

    Article  PubMed  Google Scholar 

  33. Violet J, Sandhu S, Iravani A, et al. Long-term follow-up and outcomes of re-treatment in an expanded 50 patient single-center phase II prospective trial of Lutetium-177 (177Lu) PSMA-617 theranostics in metastatic castrate-resistant prostate cancer. J Nucl Med. 2020;61:857–65. [Epub ahead of print].

    Article  PubMed  PubMed Central  Google Scholar 

  34. Kratochwil C, Bruchertseifer F, Giesel FL, et al. 225Ac-PSMA-617 for PSMA-targeted α-radiation therapy of metastatic castration resistant prostate cancer. J Nucl Med. 2016;57:1941–4.

    Article  CAS  PubMed  Google Scholar 

  35. Sathekge M, Knoesen O, Meckel M, et al. 213Bi-PSMA-617 targeted alpha-radionuclide therapy in metastatic castration-resistant prostate cancer. Eur J Nucl Med Mol Imaging. 2017;44:1099–100.

    Article  PubMed  PubMed Central  Google Scholar 

  36. Kratochwil C, Bruchertseifer F, Rathke H, et al. Targeted a-therapy of metastatic castration-resistant prostate cancer with 225Ac-PSMA-617: dosimetry estimates and empiric dose finding. J Nucl Med. 2017;58:1624–31.

    Article  CAS  PubMed  Google Scholar 

  37. Sathekge M, Bruchertseifer F, Voster M, et al. Predictive of overall survival and disease-free survival in metastatic castration-resistant prostate cancer patients receiving 225Ac-PSMA-617 radioligand therapy. J Nucl Med. 2020;61:62–9.

    Article  CAS  PubMed  Google Scholar 

  38. Sathekge M, Brucherseifer F, Knoesen O, et al. 225Ac-PSMA-617 in chemotherapy-naïve patients with advanced prostate cancer: a pilot study. Eur J Nucl Med Mol Imaging. 2019;46:129–38.

    Article  CAS  PubMed  Google Scholar 

  39. Ye Z, Qian Q, Jin H, Qian Q. Cancer vaccine: learning from immune checkpoint inhibitors. J Cancer. 2018;9:263–8.

    Article  PubMed  PubMed Central  Google Scholar 

  40. Thara E, Dorff TB, Averia-Suboc M, et al. Immune response to sipuleucel-T in prostate cancer. Cancers. 2012;4:420–41.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Singh H, Gulley JL. Immunotherapy and therapeutic vaccines in prostate cancer: an update on current strategies and clinical implications. Asian J Androl. 2014;16:364–71.

    Article  PubMed  PubMed Central  Google Scholar 

  42. Tse BW-C, Jovanovic L, Nelson CC, et al. From bench to bedside: immunotherapy for prostate cancer. Biomed Res Int. 2014;2014:981434.

    Article  PubMed  PubMed Central  Google Scholar 

  43. Kantoff PW, Higano CS, Shore ND, et al. Sipuleucel-T immunotherapy for castration-resistant prostate cancer. N Engl J Med. 2010;363:411–22.

    Article  CAS  PubMed  Google Scholar 

  44. Bilusic M, Madan RA, Gulley JL. Immunotherapy of prostate cancer: facts and hopes. Clin Cancer Res. 2017;23:6764–70.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Vitkin N, Nersessian S, Siemens DR, Koti M. The tumor immune contexture of prostate cancer. Front Immunol. 2019;10:603.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Modena A, Ciccarese C, Iacovelli R, et al. Immune checkpoint inhibitors and prostate cancer: a new frontier? Oncol Rev. 2016;10:2931.

    Google Scholar 

  47. Kittai A, Meshikhes M, Aragon-Ching JB. Ipilimumab: a potential immunologic agent in the treatment of metastatic castration-resistant prostate cancer. Cancer Biol Ther. 2014;15:1299–300.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Beer TM, Kwon ED, Drake CC, et al. Randomized double-blind phase III trial of ipilimumab versus placebo in asymptomatic or minimally symptomatic patients with metastatic chemotherapy-naïve castration-resistant prostate cancer. J Clin Oncol. 2017;35:40–7.

    Article  CAS  PubMed  Google Scholar 

  49. Kwon ED, Drake CG, Scher HI, et al. Ipilimumab versus placebo after radiotherapy in patients with metastatic castration-resistant prostate cancer that had progressed after docetaxel chemotherapy (CA184-043): a multicenter, randomized, double-blind, phase 3 trial. Lancet Oncol. 2014;15:700–12.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Hansen A, Massard C, Ott P. Pembrolizumab for patients with advanced prostate adenocarcinoma: preliminary results from KEYNOTE-028 study. Ann Oncol. 2016;27:725PD.

    Article  Google Scholar 

  51. Topalian SL, Hodi FS, Brahmer JR, et al. Safety, activity, and immune correlates of anti-PD-1 antibody in cancer. N Engl J Med. 2012;366:2443–54.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Karazi F, Madan RA, Owens H, et al. A phase II study of the anti-programmed death ligand-1 antibody durvalumab in combination with PARP inhibitor, olaparib, in metastatic castration-resistant prostate cancer (mCRPC). J Clin Oncol. 2017;35:abstr 162.

    Article  Google Scholar 

  53. Karzai F, VanderWeele D, Madan RA, et al. Activity of durvalumab plus olaparib in metastatic castration-resistant prostate cancer in men with and without DNA damage mutations. J Immunother Cancer. 2018;6:141.

    Article  PubMed  PubMed Central  Google Scholar 

  54. Malmas AS, Gameiro SR, Knudson KM, et al. Sublethal exposure to alpha radiation (223Ra dichloride) enhances various carcinoma’s sensitivity to lysis by antigen-specific cytotoxic T-lymphocytes through calreticulin-mediated immunogenic modulation. Oncotarget. 2016;7:86937–47.

    Article  Google Scholar 

  55. Schweizer MT, Drake CG. Immunotherapy for prostate cancer—recent developments and future challenges. Cancer Metastasis Rev. 2014;33:641–55.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Surdacki G, Szudy-Szczyrek A, Goracy A, et al. The role of immune checkpoint inhibitors in prostate cancer. Ann Agric Environ Med. 2019;26:120–4.

    Article  CAS  PubMed  Google Scholar 

  57. Madan RA, Gulley JL, Kantoff PW. Demystifying immunotherapy in prostate cancer: understanding current and future treatment strategies. Cancer J. 2013;19:50–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Schepisi G, Farolfi A, Conteduca V, et al. Immunotherapy for prostate cancer: where we are headed. Int J Mol Sci. 2017;18:2627.

    Article  PubMed Central  Google Scholar 

  59. Slovin SF. Emerging treatments in management of prostate cancer: biomarker validation and endpoints for immunotherapy clinical trial design. Immunotargets Ther. 2014;3:1–8.

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Division of Nuclear Medicine, Department of Radiology, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA

    Hossein Jadvar

Authors
  1. Hossein Jadvar
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Hossein Jadvar .

Editor information

Editors and Affiliations

  1. Department of Nuclear Medicine, Tehran University of Medical Sciences, Tehran, Iran

    Sara Harsini

  2. Department of Radiology, University of Pennsylvania, Philadelphia, PA, USA

    Abass Alavi

  3. Research Center for Immunodeficiencies, Tehran University of Medical Sciences, Tehran, Iran

    Nima Rezaei

Rights and permissions

Reprints and permissions

Copyright information

© 2022 Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Jadvar, H. (2022). Targeted Radionuclide Therapy and Immunotherapy of Metastatic Prostate Cancer. In: Harsini, S., Alavi, A., Rezaei, N. (eds) Nuclear Medicine and Immunology. Springer, Cham. https://doi.org/10.1007/978-3-030-81261-4_18

Download citation

  • DOI: https://doi.org/10.1007/978-3-030-81261-4_18

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-030-81260-7

  • Online ISBN: 978-3-030-81261-4

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation