Abstract
Background
Accurate staging is of major importance to determine the optimal treatment modality for patients with prostate cancer. Positron emission tomography (PET) with prostate-specific membrane antigen (PSMA) is a promising technique that outperformed conventional imaging in the detection of nodal and distant metastases in previous studies. However, it is still unclear whether the superior sensitivity and specificity also translate into improved patient management. The aim of this study was to assess the performance of 68Ga-PSMA-11 PET for staging of intermediate and high-risk prostate cancer and its potential impact on disease management.
Methods
In this retrospective analysis, 116 patients who underwent 68Ga-PSMA-11 PET/CT or MRI scans for staging of their intermediate or high-risk prostate cancer between April 2016 and May 2018 were included. The potential impact of 68Ga-PSMA-11 PET staging on patient management was assessed within a simulated multidisciplinary tumour board where hypothetical treatment decisions based on clinical information and conventional imaging alone was determined. This treatment decision was compared with the treatment recommendation based on clinical information and 68Ga-PSMA-11 PET imaging.
Results
The primary tumour was positive on 68Ga-PSMA-11 PET in 113 patients (97%). Nodal metastases were detected in 28 patients (24%) and bone metastases in 14 patients (12%). Compared with clinical staging and conventional imaging, 68Ga-PSMA-11 PET resulted in new information in 42 of 116 patients (36%). In 32 of 116 patients (27%), this information would most likely have changed the management into a different therapy modality (15 patients, 13%) or adjusted treatment details (e.g. modification of radiotherapy field or lymph node dissection template; 17 patients, 14%).
Conclusion
Information from 68Ga-PSMA-11 PET staging has the potential to change the management in more than a fourth of the patients who underwent PET staging for their intermediate to high-risk prostate cancer. Whether these more personalized 68Ga-PSMA-11 PET-based treatment decisions will improve patient outcome needs further investigation.
Similar content being viewed by others
Availability of data and material
Patient imaging was done in the scope of the routine clinical diagnostic studies, and the raw data are stored in the hospital archiving system at the Zurich University Hospital, Zurich, Switzerland.
References
Abdel-Rahman O. Assessment of the prognostic value of the 8th AJCC staging system for patients with clinically staged prostate cancer; a time to sub-classify stage IV? PLoS One. 2017;12:e0188450. https://doi.org/10.1371/journal.pone.0188450.
American Joint Committee on C, Amin MB. AJCC cancer staging manual. New York: Springer; 2017.
Mottet N, Bellmunt J, Bolla M, Briers E, Cumberbatch MG, De Santis M, et al. EAU-ESTRO-SIOG guidelines on prostate cancer. Part 1: screening, diagnosis, and local treatment with curative intent. Eur Urol. 2017;71:618–29. https://doi.org/10.1016/j.eururo.2016.08.003.
de Rooij M, Hamoen EH, Witjes JA, Barentsz JO, Rovers MM. Accuracy of magnetic resonance imaging for local staging of prostate cancer: a diagnostic meta-analysis. Eur Urol. 2016;70:233–45. https://doi.org/10.1016/j.eururo.2015.07.029.
Hovels AM, Heesakkers RA, Adang EM, Jager GJ, Strum S, Hoogeveen YL, et al. The diagnostic accuracy of CT and MRI in the staging of pelvic lymph nodes in patients with prostate cancer: a meta-analysis. Clin Radiol. 2008;63:387–95. https://doi.org/10.1016/j.crad.2007.05.022.
Briganti A, Abdollah F, Nini A, Suardi N, Gallina A, Capitanio U, et al. Performance characteristics of computed tomography in detecting lymph node metastases in contemporary patients with prostate cancer treated with extended pelvic lymph node dissection. Eur Urol. 2012;61:1132–8. https://doi.org/10.1016/j.eururo.2011.11.008.
Even-Sapir E, Metser U, Mishani E, Lievshitz G, Lerman H, Leibovitch I. The detection of bone metastases in patients with high-risk prostate cancer: 99mTc-MDP Planar bone scintigraphy, single- and multi-field-of-view SPECT, 18F-fluoride PET, and 18F-fluoride PET/CT. J Nucl Med. 2006;47:287–97.
Gabriele D, Collura D, Oderda M, Stura I, Fiorito C, Porpiglia F, et al. Is there still a role for computed tomography and bone scintigraphy in prostate cancer staging? An analysis from the EUREKA-1 database. World J Urol. 2016;34:517–23. https://doi.org/10.1007/s00345-015-1669-2.
Abuzallouf S, Dayes I, Lukka H. Baseline staging of newly diagnosed prostate cancer: a summary of the literature. J Urol. 2004;171:2122–7.
Evangelista L, Cimitan M, Zattoni F, Guttilla A, Zattoni F, Saladini G. Comparison between conventional imaging (abdominal-pelvic computed tomography and bone scan) and [(18)F]choline positron emission tomography/computed tomography imaging for the initial staging of patients with intermediate- to high-risk prostate cancer: a retrospective analysis. Scand J Urol. 2015;49:345–53. https://doi.org/10.3109/21681805.2015.1005665.
von Eyben FE, Kairemo K. Meta-analysis of (11)C-choline and (18)F-choline PET/CT for management of patients with prostate cancer. Nucl Med Commun. 2014;35:221–30. https://doi.org/10.1097/MNM.0000000000000040.
Van den Bergh L, Lerut E, Haustermans K, Deroose CM, Oyen R, Isebaert S, et al. Final analysis of a prospective trial on functional imaging for nodal staging in patients with prostate cancer at high risk for lymph node involvement. Urol Oncol. 2015;33:109 e23–31. https://doi.org/10.1016/j.urolonc.2014.11.008.
Morigi JJ, Stricker PD, van Leeuwen PJ, Tang R, Ho B, Nguyen Q, et al. Prospective comparison of 18F-fluoromethylcholine versus 68Ga-PSMA PET/CT in prostate cancer patients who have rising PSA after curative treatment and are being considered for targeted therapy. J Nucl Med. 2015;56:1185–90. https://doi.org/10.2967/jnumed.115.160382.
Evangelista L, Briganti A, Fanti S, Joniau S, Reske S, Schiavina R, et al. New clinical indications for (18)F/(11)C-choline, new tracers for positron emission tomography and a promising hybrid device for prostate cancer staging: a systematic review of the literature. Eur Urol. 2016;70:161–75. https://doi.org/10.1016/j.eururo.2016.01.029.
Schwenck J, Rempp H, Reischl G, Kruck S, Stenzl A, Nikolaou K, et al. Comparison of (68)Ga-labelled PSMA-11 and (11)C-choline in the detection of prostate cancer metastases by PET/CT. Eur J Nucl Med Mol Imaging. 2017;44:92–101. https://doi.org/10.1007/s00259-016-3490-6.
Perera M, Papa N, Christidis D, Wetherell D, Hofman MS, Murphy DG, et al. Sensitivity, specificity, and predictors of positive (68)Ga-prostate-specific membrane antigen positron emission tomography in advanced prostate cancer: a systematic review and meta-analysis. Eur Urol. 2016;70:926–37. https://doi.org/10.1016/j.eururo.2016.06.021.
Park SY, Zacharias C, Harrison C, Fan RE, Kunder C, Hatami N, et al. Gallium 68 PSMA-11 PET/MR imaging in patients with intermediate- or high-risk prostate cancer. Radiology. 2018;172232. https://doi.org/10.1148/radiol.2018172232.
Eiber M, Weirich G, Holzapfel K, Souvatzoglou M, Haller B, Rauscher I, et al. Simultaneous (68)Ga-PSMA HBED-CC PET/MRI improves the localization of primary prostate cancer. Eur Urol. 2016;70:829–36. https://doi.org/10.1016/j.eururo.2015.12.053.
Afshar-Oromieh A, Holland-Letz T, Giesel FL, Kratochwil C, Mier W, Haufe S, et al. Diagnostic performance of (68)Ga-PSMA-11 (HBED-CC) PET/CT in patients with recurrent prostate cancer: evaluation in 1007 patients. Eur J Nucl Med Mol Imaging. 2017;44:1258–68. https://doi.org/10.1007/s00259-017-3711-7.
Afshar-Oromieh A, Zechmann CM, Malcher A, Eder M, Eisenhut M, Linhart HG, et al. Comparison of PET imaging with a Ga-68-labelled PSMA ligand and F-18-choline-based PET/CT for the diagnosis of recurrent prostate cancer. Eur J Nucl Med Mol I. 2014;41:11–20. https://doi.org/10.1007/s00259-013-2525-5.
Pyka T, Okamoto S, Dahlbender M, Tauber R, Retz M, Heck M, et al. Comparison of bone scintigraphy and (68)Ga-PSMA PET for skeletal staging in prostate cancer. Eur J Nucl Med Mol Imaging. 2016;43:2114–21. https://doi.org/10.1007/s00259-016-3435-0.
Maurer T, Gschwend JE, Rauscher I, Souvatzoglou M, Haller B, Weirich G, et al. Diagnostic efficacy of (68)gallium-PSMA positron emission tomography compared to conventional imaging for lymph node staging of 130 consecutive patients with intermediate to high risk prostate cancer. J Urol. 2016;195:1436–43. https://doi.org/10.1016/j.juro.2015.12.025.
Obek C, Doganca T, Demirci E, Ocak M, Kural AR, Yildirim A, et al. The accuracy of (68)Ga-PSMA PET/CT in primary lymph node staging in high-risk prostate cancer. Eur J Nucl Med Mol Imaging. 2017;44:1806–12. https://doi.org/10.1007/s00259-017-3752-y.
Giesel FL, Fiedler H, Stefanova M, Sterzing F, Rius M, Kopka K, et al. PSMA PET/CT with Glu-urea-Lys-(Ahx)-[(6)(8)Ga(HBED-CC)] versus 3D CT volumetric lymph node assessment in recurrent prostate cancer. Eur J Nucl Med Mol Imaging. 2015;42:1794–800. https://doi.org/10.1007/s00259-015-3106-6.
Berger I, Annabattula C, Lewis J, Shetty DV, Kam J, Maclean F, et al. (68)Ga-PSMA PET/CT vs. mpMRI for locoregional prostate cancer staging: correlation with final histopathology. Prostate Cancer Prostatic Dis. 2018;21:204–11. https://doi.org/10.1038/s41391-018-0048-7.
Roach PJ, Francis R, Emmett L, Hsiao E, Kneebone A, Hruby G, et al. The impact of (68)Ga-PSMA PET/CT on management intent in prostate cancer: results of an Australian prospective multicenter study. J Nucl Med. 2018;59:82–8. https://doi.org/10.2967/jnumed.117.197160.
Hruby G, Eade T, Emmett L, Ho B, Hsiao E, Schembri G, et al. (68) Ga-PSMA-PET/CT staging prior to definitive radiation treatment for prostate cancer. Asia Pac J Clin Oncol. 2018. https://doi.org/10.1111/ajco.12872.
Sterzing F, Kratochwil C, Fiedler H, Katayama S, Habl G, Kopka K, et al. (68)Ga-PSMA-11 PET/CT: a new technique with high potential for the radiotherapeutic management of prostate cancer patients. Eur J Nucl Med Mol Imaging. 2016;43:34–41. https://doi.org/10.1007/s00259-015-3188-1.
Koerber SA, Will L, Kratochwil C, Haefner MF, Rathke H, Kremer C, et al. (68)Ga-PSMA-11 PET/CT in primary and recurrent prostate carcinoma: implications for radiotherapeutic management in 121 patients. J Nucl Med. 2018. https://doi.org/10.2967/jnumed.118.211086.
Eissa A, El Sherbiny A, Coelho RF, Rassweiler J, Davis JW, Porpiglia F, et al. The role of 68Ga-PSMA PET/CT scan in biochemical recurrence after primary treatment for prostate cancer: a systematic review of literature. Minerva Urol Nefrol. 2018. https://doi.org/10.23736/S0393-2249.18.03081-3.
Mena E, Lindenberg ML, Shih JH, Adler S, Harmon S, Bergvall E, et al. Clinical impact of PSMA-based (18)F-DCFBC PET/CT imaging in patients with biochemically recurrent prostate cancer after primary local therapy. Eur J Nucl Med Mol Imaging. 2018;45:4–11. https://doi.org/10.1007/s00259-017-3818-x.
Han S, Woo S, Kim YJ, Suh CH. Impact of (68)Ga-PSMA PET on the management of patients with prostate cancer: a systematic review and meta-analysis. Eur Urol. 2018. https://doi.org/10.1016/j.eururo.2018.03.030.
Calais J, Fendler WP, Eiber M, Gartmann J, Chu FI, Nickols NG, et al. Impact of (68)Ga-PSMA-11 PET/CT on the management of prostate cancer patients with biochemical recurrence. J Nucl Med. 2018;59:434–41. https://doi.org/10.2967/jnumed.117.202945.
Muller J, Ferraro DA, Muehlematter UJ, Garcia Schuler HI, Kedzia S, Eberli D, et al. Clinical impact of (68)Ga-PSMA-11 PET on patient management and outcome, including all patients referred for an increase in PSA level during the first year after its clinical introduction. Eur J Nucl Med Mol Imaging. 2018. https://doi.org/10.1007/s00259-018-4203-0.
European Association of Urology. Oncology guidelines: prostate cancer. 2018.
Grubmuller B, Baltzer P, Hartenbach S, D'Andrea D, Helbich TH, Haug AR, et al. PSMA ligand PET/MRI for primary prostate cancer: staging performance and clinical impact. Clin Cancer Res. 2018;24:6300–7. https://doi.org/10.1158/1078-0432.CCR-18-0768.
D'Amico AV, Whittington R, Malkowicz SB, Schultz D, Blank K, Broderick GA, et al. Biochemical outcome after radical prostatectomy, external beam radiation therapy, or interstitial radiation therapy for clinically localized prostate cancer. JAMA. 1998;280:969–74.
Cornford P, Bellmunt J, Bolla M, Briers E, De Santis M, Gross T, et al. EAU-ESTRO-SIOG guidelines on prostate cancer. Part II: treatment of relapsing, metastatic, and castration-resistant prostate cancer. Eur Urol. 2017;71:630–42. https://doi.org/10.1016/j.eururo.2016.08.002.
Kranzbuhler B, Nagel H, Becker AS, Muller J, Huellner M, Stolzmann P, et al. Clinical performance of (68)Ga-PSMA-11 PET/MRI for the detection of recurrent prostate cancer following radical prostatectomy. Eur J Nucl Med Mol Imaging. 2018;45:20–30. https://doi.org/10.1007/s00259-017-3850-x.
Hofman MS, Hicks RJ, Maurer T, Eiber M. Prostate-specific membrane antigen PET: clinical utility in prostate cancer, normal patterns, pearls, and pitfalls. Radiographics. 2018;38:200–17. https://doi.org/10.1148/rg.2018170108.
Fendler WP, Calais J, Allen-Auerbach M, Bluemel C, Eberhardt N, Emmett L, et al. (68)Ga-PSMA-11 PET/CT interobserver agreement for prostate cancer assessments: an international multicenter prospective study. J Nucl Med. 2017;58:1617–23. https://doi.org/10.2967/jnumed.117.190827.
Calais J, Kishan AU, Cao M, Fendler WP, Eiber M, Herrmann K, et al. Potential impact of (68)Ga-PSMA-11 PET/CT on prostate cancer definitive radiation therapy planning. J Nucl Med. 2018. https://doi.org/10.2967/jnumed.118.209387.
Uprimny C, Kroiss AS, Decristoforo C, Fritz J, von Guggenberg E, Kendler D, et al. (68)Ga-PSMA-11 PET/CT in primary staging of prostate cancer: PSA and Gleason score predict the intensity of tracer accumulation in the primary tumour. Eur J Nucl Med Mol Imaging. 2017;44:941–9. https://doi.org/10.1007/s00259-017-3631-6.
Budaus L, Leyh-Bannurah SR, Salomon G, Michl U, Heinzer H, Huland H, et al. Initial experience of (68)Ga-PSMA PET/CT imaging in high-risk prostate cancer patients prior to radical prostatectomy. Eur Urol. 2016;69:393–6. https://doi.org/10.1016/j.eururo.2015.06.010.
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.
Mannweiler S, Amersdorfer P, Trajanoski S, Terrett JA, King D, Mehes G. Heterogeneity of prostate-specific membrane antigen (PSMA) expression in prostate carcinoma with distant metastasis. Pathol Oncol Res. 2009;15:167–72. https://doi.org/10.1007/s12253-008-9104-2.
Wright GL Jr, Haley C, Beckett ML, Schellhammer PF. Expression of prostate-specific membrane antigen in normal, benign, and malignant prostate tissues. Urol Oncol. 1995;1:18–28.
Hupe MC, Philippi C, Roth D, Kumpers C, Ribbat-Idel J, Becker F, et al. Expression of prostate-specific membrane antigen (PSMA) on biopsies is an independent risk stratifier of prostate cancer patients at time of initial diagnosis. Front Oncol. 2018;8:623. https://doi.org/10.3389/fonc.2018.00623.
Giesel FL, Hadaschik B, Cardinale J, Radtke J, Vinsensia M, Lehnert W, et al. F-18 labelled PSMA-1007: biodistribution, radiation dosimetry and histopathological validation of tumor lesions in prostate cancer patients. Eur J Nucl Med Mol Imaging. 2017;44:678–88. https://doi.org/10.1007/s00259-016-3573-4.
Giesel FL, Will L, Lawal I, Lengana T, Kratochwil C, Vorster M, et al. Intraindividual comparison of (18)F-PSMA-1007 and (18)F-DCFPyL PET/CT in the prospective evaluation of patients with newly diagnosed prostate carcinoma: a pilot study. J Nucl Med. 2018;59:1076–80. https://doi.org/10.2967/jnumed.117.204669.
Briganti A, Passoni N, Ferrari M, Capitanio U, Suardi N, Gallina A, et al. When to perform bone scan in patients with newly diagnosed prostate cancer: external validation of the currently available guidelines and proposal of a novel risk stratification tool. Eur Urol. 2010;57:551–8. https://doi.org/10.1016/j.eururo.2009.12.023.
Vargas HA, Schor-Bardach R, Long N, Kirzner AN, Cunningham JD, Goldman DA, et al. Prostate cancer bone metastases on staging prostate MRI: prevalence and clinical features associated with their diagnosis. Abdom Radiol (NY). 2017;42:271–7. https://doi.org/10.1007/s00261-016-0851-3.
Norgaard M, Jensen AO, Jacobsen JB, Cetin K, Fryzek JP, Sorensen HT. Skeletal related events, bone metastasis and survival of prostate cancer: a population based cohort study in Denmark (1999 to 2007). J Urol. 2010;184:162–7. https://doi.org/10.1016/j.juro.2010.03.034.
Dyrberg E, Hendel HW, Huynh THV, Klausen TW, Logager VB, Madsen C, et al. (68)Ga-PSMA-PET/CT in comparison with (18)F-fluoride-PET/CT and whole-body MRI for the detection of bone metastases in patients with prostate cancer: a prospective diagnostic accuracy study. Eur Radiol. 2019;29:1221–30. https://doi.org/10.1007/s00330-018-5682-x.
Zacho HD, Nielsen JB, Afshar-Oromieh A, Haberkorn U, de Souza N, De Paepe K, et al. Prospective comparison of (68)Ga-PSMA PET/CT, (18)F-sodium fluoride PET/CT and diffusion weighted-MRI at for the detection of bone metastases in biochemically recurrent prostate cancer. Eur J Nucl Med Mol Imaging. 2018;45:1884–97. https://doi.org/10.1007/s00259-018-4058-4.
Lengana T, Lawal IO, Boshomane TG, Popoola GO, Mokoala KMG, Moshokoa E, et al. (68)Ga-PSMA PET/CT replacing bone scan in the initial staging of skeletal metastasis in prostate cancer: a fait accompli? Clin Genitourin Cancer. 2018;16:392–401. https://doi.org/10.1016/j.clgc.2018.07.009.
Yaxley JW, Raveenthiran S, Nouhaud FX, Samaratunga H, Yaxley WJ, Coughlin G, et al. Risk of metastatic disease on (68) Ga-PSMA PET/CT scan for primary staging of 1253 men at the diagnosis of prostate cancer. BJU Int. 2019. https://doi.org/10.1111/bju.14828.
Wong HS, Leung J, Bartholomeusz D, Sutherland P, Le H, Nottage M, et al. Comparative study between (68) Ga-prostate-specific membrane antigen positron emission tomography and conventional imaging in the initial staging of prostate cancer. J Med Imaging Radiat Oncol. 2018;62:816–22. https://doi.org/10.1111/1754-9485.12791.
Skove SL, Howard LE, Aronson WJ, Terris MK, Kane CJ, Amling CL, et al. Timing of prostate-specific antigen nadir after radical prostatectomy and risk of biochemical recurrence. Urology. 2017;108:129–34. https://doi.org/10.1016/j.urology.2017.07.009.
Acknowledgements
The authors acknowledge the technicians Marlena Hofbauer and Josephine Trinckauf and their team for the excellent work on high-quality PET images.
Funding
The Department of Nuclear Medicine holds an institutional Research Contract with GE Healthcare. The authors thank the Sick legat and the Iten-Kohaut foundation for their financial support.
Author information
Authors and Affiliations
Contributions
DAF and HIGS—data collection, analysis, and manuscript writing
UJM and JM—data collection
DE, PAK—manuscript revision
AM, RG, HK, AO—patient selection and manuscript revision
TH, IAB—study design, manuscript writing
All authors reviewed and agreed to the manuscript content.
Corresponding author
Ethics declarations
Ethics approval and consent to participate
The local ethics committee approved the study protocol and all patients gave a general written informed consent for retrospective use of their data (BASEC Nr. 2018-01284).
Consent for publication
Not applicable.
Competing interests
IAB has received research grants and speaker honorarium from GE Healthcare, research grants from Swiss Life and speaker honorarium from Bayer Health Care and Astellas Pharma AG. TH holds an advisory function for MSD and Bayer. AO declares an advisory role (compensated, institutional) for Astra Zeneca, Astellas, Bayer, Janssen, Molecular Partners, MSD, Pfizer, Roche, Sanofi Aventis; research support (institutional) from TEVA, Janssen; travel support from Astellas, Bayer, Janssen, Sanofi Aventis and speakers bureau (compensated, institutional) from Bayer, Astellas. Authors DAF, HIGS, UJM, DE, JM, AM, RG, HK, and PAK declare no conflict of interest.
Additional information
Publisher’s note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
This article is part of the Topical Collection on Oncology – Genitourinary
Electronic supplementary material
ESM 1
(DOCX 41 kb)
Rights and permissions
About this article
Cite this article
Ferraro, D.A., Garcia Schüler, H.I., Muehlematter, U.J. et al. Impact of 68Ga-PSMA-11 PET staging on clinical decision-making in patients with intermediate or high-risk prostate cancer. Eur J Nucl Med Mol Imaging 47, 652–664 (2020). https://doi.org/10.1007/s00259-019-04568-1
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00259-019-04568-1