Skip to main content
SpringerLink
Log in

PSMA PET applications in the prostate cancer journey: from diagnosis to theranostics

  • Topic Paper
  • Published:
World Journal of Urology Aims and scope Submit manuscript

Abstract

The heterogeneity of prostate cancer has made imaging modalities of crucial importance in this disease. Accurate diagnosis and staging of the volume and extent of disease, especially in advanced and metastatic prostate cancer, can help to tailor the timing and modalities of treatment. While MRI has been effective in the detection of significant prostate cancer, its use in the identification and quantification of extraprostatic disease is limited. This gap is now being filled by PSMA PET. PSMA PET scans have now been shown to have a role in all stages in the prostate cancer journey. Emerging evidence has shown its promise in primary staging, restaging and theranostics. In this paper, we review the evidence for the use of PSMA PET in the various stages of prostate cancer, from initial diagnosis to advanced metastatic disease where other systemic treatments have failed.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig 1
Fig 2

Similar content being viewed by others

References

  1. Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J, Jemal A (2015) Global cancer statistics, 2012. CA Cancer J Clin 65:87–108

    Article  PubMed  Google Scholar 

  2. Bartsch G, Horninger W, Klocker H, Reissigl A, Oberaigner W, Schonitzer D et al (2001) Prostate cancer mortality after introduction of prostate-specific antigen mass screening in the Federal State of Tyrol Austria. Urology 58:417–424

    Article  CAS  PubMed  Google Scholar 

  3. Tosoian JJ, Gorin MA, Ross AE, Pienta KJ, Tran PT, Schaeffer EM (2017) Oligometastatic prostate cancer: definitions, clinical outcomes, and treatment considerations. Nat Rev Urol 14:15–25

    Article  CAS  PubMed  Google Scholar 

  4. Toner L, Papa N, Perera M, Katelaris N, Weerakoon M, Chin K et al (2017) Multiparametric magnetic resonance imaging for prostate cancer—a comparative study including radical prostatectomy specimens. World J Urol 35:935–941

    Article  CAS  PubMed  Google Scholar 

  5. Calopedos RJS, Chalasani V, Asher R, Emmett L, Woo HH (2017) 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 20:352–360

    Article  CAS  PubMed  Google Scholar 

  6. Hofman MS, Violet J, Hicks RJ, Ferdinandus J, Thang SP, Akhurst T et al (2018) [(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 19:825–833

    Article  CAS  PubMed  Google Scholar 

  7. Silver DA, Pellicer I, Fair WR, Heston WDW, CordonCardo C (1997) Prostate-specific membrane antigen expression in normal and malignant human tissues. Clin Cancer Res 3:81–85

    CAS  PubMed  Google Scholar 

  8. DeMarzo AM, Nelson WG, Isaacs WB, Epstein JI (2003) Pathological and molecular aspects of prostate cancer. Lancet 361:955–964

    Article  CAS  PubMed  Google Scholar 

  9. Sweat SD, Pacelli A, Murphy GP, Bostwick DG (1998) Prostate-specific membrane antigen expression is greatest in prostate adenocarcinoma and lymph node metastases. Urology 52:637–640

    Article  CAS  PubMed  Google Scholar 

  10. Bostwick DG, Pacelli A, Blute M, Roche P, Murphy GP (1998) Prostate specific membrane antigen expression in prostatic intraepithelial neoplasia and adenocarcinoma: a study of 184 cases. Cancer 82:2256–2261

    Article  CAS  PubMed  Google Scholar 

  11. Evans MJ, Smith-Jones PM, Wongvipat J, Navarro V, Kim S, Bander NH et al (2011) Noninvasive measurement of androgen receptor signaling with a positron-emitting radiopharmaceutical that targets prostate-specific membrane antigen. Proc Natl Acad Sci USA 108:9578–9582

    Article  PubMed  PubMed Central  Google Scholar 

  12. Afshar-Oromieh A, Zechmann CM, Malcher A, Eder M, Eisenhut M, Linhart HG et al (2014) Comparison of PET imaging with a (68)Ga-labelled PSMA ligand and (18)F-choline-based PET/CT for the diagnosis of recurrent prostate cancer. Eur J Nucl Med Mol Imaging 41:11–20

    Article  CAS  PubMed  Google Scholar 

  13. Fenton JJ, Weyrich MS, Durbin S, Liu Y, Bang H, Melnikow J (2018) Prostate-specific antigen-based screening for prostate cancer: evidence report and systematic review for the us preventive services task force. JAMA 319:1914–1931

    Article  PubMed  Google Scholar 

  14. Ahmed HU, El-Shater Bosaily A, Brown LC, Gabe R, Kaplan R, Parmar MK et al (2017) Diagnostic accuracy of multi-parametric MRI and TRUS biopsy in prostate cancer (PROMIS): a paired validating confirmatory study. Lancet 389:815–822

    Article  PubMed  Google Scholar 

  15. Kasivisvanathan V, Rannikko AS, Borghi M, Panebianco V, Mynderse LA, Vaarala MH et al (2018) MRI-targeted or standard biopsy for prostate-cancer diagnosis. New Engl J Med 378:1767–1777

    Article  PubMed  Google Scholar 

  16. Eiber M, Weirich G, Holzapfel K, Souvatzoglou M, Haller B, Rauscher I et al (2016) Simultaneous (68)Ga-PSMA HBED-CC PET/MRI improves the localization of primary prostate cancer. Eur Urol 70:829–836

    Article  CAS  PubMed  Google Scholar 

  17. Lopci E, Saita A, Lazzeri M, Lughezzani G, Colombo P, Buffi NM et al (2018) (68)Ga-PSMA positron emission tomography/computerized tomography for primary diagnosis of prostate cancer in men with contraindications to or negative multiparametric magnetic resonance imaging: a prospective observational study. J Urol 200:95–103

    Article  PubMed  Google Scholar 

  18. Hovels AM, Heesakkers RA, Adang EM, Jager GJ, Strum S, Hoogeveen YL et al (2008) The diagnostic accuracy of CT and MRI in the staging of pelvic lymph nodes in patients with prostate cancer: a meta-analysis. Clin Radiol 63:387–395

    Article  CAS  PubMed  Google Scholar 

  19. Corfield J, Perera M, Bolton D, Lawrentschuk N (2018) (68)Ga-prostate specific membrane antigen (PSMA) positron emission tomography (PET) for primary staging of high-risk prostate cancer: a systematic review. World J Urol 36:519–527

    Article  PubMed  Google Scholar 

  20. Hofman MS, Hicks RJ, Maurer T, Eiber M (2018) Prostate-specific membrane antigen PET: clinical utility in prostate cancer, normal patterns, pearls, and pitfalls. Radiographics 38:200–217

    Article  PubMed  Google Scholar 

  21. van Leeuwen PJ, Emmett L, Ho B, Delprado W, Ting F, Nguyen Q et al (2017) Prospective evaluation of 68Gallium-prostate-specific membrane antigen positron emission tomography/computed tomography for preoperative lymph node staging in prostate cancer. BJU Int 119:209–215

    Article  CAS  PubMed  Google Scholar 

  22. Isabel R, Charlotte D, Martina W, Margret S, Hans-Jürgen W, Kristina S et al (2017) Value of 111In-prostate-specific membrane antigen (PSMA)-radioguided surgery for salvage lymphadenectomy in recurrent prostate cancer: correlation with histopathology and clinical follow-up. BJU Int 120:40–47

    Article  CAS  Google Scholar 

  23. Geurts N, Lamb AD, Lawrentschuk N, Murphy DG (2017) Prostate-specific membrane antigen radioguided surgery: a promising utility. BJU Int 120:5–6

    Article  PubMed  Google Scholar 

  24. Murphy DG, Hofman M, Lawrentschuk N, Maurer T (2017) Bringing clarity or confusion? The role of prostate-specific membrane antigen positron-emission/computed tomography for primary staging in prostate cancer. BJU Int 119:194–195

    Article  PubMed  Google Scholar 

  25. Hofman, Murphy DG, Williams SG, Nzenza T, Herschtal A, Lourenco RA et al (2018) A prospective randomized multicentre study of the impact of gallium-68 prostate-specific membrane antigen (PSMA) PET/CT imaging for staging high-risk prostate cancer prior to curative-intent surgery or radiotherapy (proPSMA study): clinical trial protocol. BJU Int. https://doi.org/10.1111/bju.14374 [Epub ahead of print]

    Article  PubMed  Google Scholar 

  26. Bluemel C, Linke F, Herrmann K, Simunovic I, Eiber M, Kestler C et al (2016) Impact of (68)Ga-PSMA PET/CT on salvage radiotherapy planning in patients with prostate cancer and persisting PSA values or biochemical relapse after prostatectomy. EJNMMI Res 6:78

    Article  PubMed  PubMed Central  Google Scholar 

  27. Perera M, Papa N, Christidis D, Wetherell D, Hofman MS, Murphy DG et al (2016) Sensitivity, specificity, and predictors of positive 68Ga-prostate-specific membrane antigen positron emission tomography in advanced prostate cancer: a systematic review and meta-analysis. Eur Urol 70:926–937

    Article  PubMed  Google Scholar 

  28. von Eyben FE, Picchio M, von Eyben R, Rhee H, Bauman G (2016) (68)Ga-Labeled Prostate-specific membrane antigen ligand positron emission tomography/computed tomography for prostate cancer: a systematic review and meta-analysis. Eur Urol Focus. https://doi.org/10.1016/j.euf.2016.11.002

    Article  Google Scholar 

  29. Han S, Woo S, Kim YJ, Suh CH (2018) Impact of 68Ga-PSMA PET on the management of patients with prostate cancer: a systematic review and meta-analysis. Eur Urol 74:179–190

    Article  CAS  PubMed  Google Scholar 

  30. van Leeuwen PJ, Stricker P, Hruby G, Kneebone A, Ting F, Thompson B et al (2016) (68) Ga-PSMA has a high detection rate of prostate cancer recurrence outside the prostatic fossa in patients being considered for salvage radiation treatment. BJU Int 117:732–739

    Article  CAS  PubMed  Google Scholar 

  31. Hicks RJ, Murphy DG, Williams SG (2017) Seduction by sensitivity: reality, illusion, or delusion? The challenge of assessing outcomes after PSMA imaging selection of patients for treatment. J Nucl Med 58:1969–1971

    Article  CAS  PubMed  Google Scholar 

  32. EAU (2018) EAU guidelines 2018 edition. Prostate cancer. EAU, Arnhem, p 2018

    Google Scholar 

  33. Clarebrough E, Duncan C, Christidis D, Lavoipierre A, Lawrentschuk N (2018) PSMA-PET guided hook-wire localization of nodal metastases in prostate cancer: a targeted approach. World J Urol. https://doi.org/10.1007/s00345-018-2282-y

    Article  PubMed  Google Scholar 

  34. Murphy DG, Sweeney CJ, Tombal B (2017) “Gotta catch ‘em all”, or do we? Pokemet approach to metastatic prostate cancer. Eur Urol 72:1–3

    Article  PubMed  Google Scholar 

  35. Nair R, Lamb BW, Geurts N, Alghazo O, Lam W, Lawrentschuk N et al (2017) The role of local therapy for oligometastatic prostate cancer: should we expect a cure? Urol Clin N Am 44:623–633

    Article  Google Scholar 

  36. Hertz BE, Schuller KE (2010) Saul Hertz, MD (1905–1950): a pioneer in the use of radioactive iodine. Endocr Pract 16:713–715

    Article  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  38. Yadav MP, Ballal S, Tripathi M, Damle NA, Sahoo RK, Seth A et al (2017) (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 44:81–91

    Article  CAS  PubMed  Google Scholar 

  39. Ahmadzadehfar H, Rahbar K, Kurpig S, Bogemann M, Claesener M, Eppard E et al (2015) 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 5:114

    PubMed  Google Scholar 

  40. Fendler WP, Reinhardt S, Ilhan H, Delker A, Boning G, Gildehaus FJ et al (2017) Preliminary experience with dosimetry, response and patient reported outcome after 177Lu-PSMA-617 therapy for metastatic castration-resistant prostate cancer. Oncotarget 8:3581–3590

    Article  PubMed  Google Scholar 

  41. Kratochwil C, Giesel FL, Stefanova M, Benesova M, Bronzel M, Afshar-Oromieh A et al (2016) PSMA-targeted radionuclide therapy of metastatic castration-resistant prostate cancer with 177Lu-labeled PSMA-617. J Nucl Med 57:1170–1176

    Article  CAS  PubMed  Google Scholar 

  42. Heck MM, Retz M, D’Alessandria C, Rauscher I, Scheidhauer K, Maurer T et al (2016) Systemic radioligand therapy with (177)Lu labeled prostate specific membrane antigen ligand for imaging and therapy in patients with metastatic castration resistant prostate cancer. J Urol 196:382–391

    Article  CAS  PubMed  Google Scholar 

  43. Baum RP, Kulkarni HR, Schuchardt C, Singh A, Wirtz M, Wiessalla S et al (2016) 177Lu-labeled prostate-specific membrane antigen radioligand therapy of metastatic castration-resistant prostate cancer: safety and efficacy. J Nucl Med 57:1006–1013

    Article  CAS  PubMed  Google Scholar 

  44. Kulkarni HR, Singh A, Schuchardt C, Niepsch K, Sayeg M, Leshch Y et al (2016) PSMA-based radioligand therapy for metastatic castration-resistant prostate cancer: the Bad Berka experience since 2013. J Nucl Med 57:97s–104s

    Article  CAS  PubMed  Google Scholar 

  45. de Bono JS, Oudard S, Ozguroglu M, Hansen S, Machiels JP, Kocak I et al (2010) Prednisone plus cabazitaxel or mitoxantrone for metastatic castration-resistant prostate cancer progressing after docetaxel treatment: a randomised open-label trial. Lancet 376:1147–1154

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Division of Cancer Surgery, Peter MacCallum Cancer Centre, Melbourne, Australia

    R. S. Eapen, T. C. Nzenza, D. G. Murphy & N. Lawrentschuk

  2. Department of Surgery, University of Melbourne, Austin Hospital, Melbourne, Australia

    R. S. Eapen, T. C. Nzenza & N. Lawrentschuk

  3. Olivia Newton-John Cancer Research Institute, Austin Hospital, Melbourne, Australia

    R. S. Eapen, T. C. Nzenza & N. Lawrentschuk

  4. Young Urology Researchers Organisation (YURO), Melbourne, Australia

    T. C. Nzenza

  5. Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, Australia

    D. G. Murphy & M. S. Hofman

  6. Department of Molecular Imaging, Peter MacCallum Cancer Centre, Melbourne, Australia

    M. S. Hofman

  7. Department of Urology, Helen Diller Comprehensive Cancer Centre, University of California, San Francisco, USA

    M. Cooperberg

  8. Department of Urology, Austin Hospital, Melbourne, Australia

    R. S. Eapen

Authors
  1. R. S. Eapen
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. T. C. Nzenza
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. D. G. Murphy
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. M. S. Hofman
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. M. Cooperberg
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. N. Lawrentschuk
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

RSE Joint 1st author. Project development, evidence analysis, manuscript writing; TCN Joint 1st author. Project development, evidence analysis, manuscript writing; DGM Evidence analysis, manuscript editing, figures; MSH Evidence analysis, manuscript editing; MC manuscript editing and approval; NL manuscript editing and approval

Corresponding author

Correspondence to R. S. Eapen.

Ethics declarations

Conflict of interest

The authors declare that there are no conflicts of interest regarding the publication of this paper. As this is a review of the current literature, there were no human participants or animals involved.

Additional information

RS Eapen and TC Nzenza are joint first authors.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Eapen, R.S., Nzenza, T.C., Murphy, D.G. et al. PSMA PET applications in the prostate cancer journey: from diagnosis to theranostics. World J Urol 37, 1255–1261 (2019). https://doi.org/10.1007/s00345-018-2524-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00345-018-2524-z

Keywords

Search

Navigation