68Ga-PSMA PET/CT compared with MRI/CT and diffusion-weighted MRI for primary lymph node staging prior to definitive radiotherapy in prostate cancer: a prospective diagnostic test accuracy study

  • Lars J. PetersenEmail author
  • Julie B. Nielsen
  • Niels C. Langkilde
  • Astrid Petersen
  • Ali Afshar-Oromieh
  • Nandita M. De Souza
  • Katja De Paepe
  • Rune V. Fisker
  • Dennis T. Arp
  • Jesper Carl
  • Uwe Haberkorn
  • Helle D. Zacho
Original Article



The aim was to compare the diagnostic accuracy of 68Ga-PSMA PET/CT with conventional cross-sectional imaging and diffusion-weighted MRI (DW-MRI) for detecting lymph node metastasis (LNM) to stage prostate cancer patients. Twenty consecutive, newly- diagnosed prostate cancer patients were prospectively enrolled and underwent 68Ga-PSMA-11 PET/CT, anatomical MRI or contrast-enhanced CT, and DW-MRI prior to laparoscopic, template-based, extended lymph node dissection. Histopathological findings served as the reference test.


Histopathology showed LNM in 13 of 20 patients (19 high-risk, 1 intermediate risk). Five patients had metastasis-suspected lymph nodes on 68Ga-PSMA PET/CT. Patient-based analysis showed that the sensitivity and specificity for detecting LNM were 39% and 100% with 68Ga-PSMA PET/CT, 8% and 100% with MRI/CT, and 36% and 83% with DW-MRI, respectively. The positive and negative predictive values were 100% and 49% with 68Ga-PSMA PET/C, 100% and 37% with MRI/CT, and 80% and 42% with DW-MRI. Of 573 dissected lymph nodes, 33 were LNM from 26 regions. True-positive LNM on 68Ga-PSMA PET/CT was 9–11 mm in diameter, whereas false-negative LNM had a median diameter of 4 mm, with only 3 of 30 lymph nodes being larger than 10 mm. LNM were positive for PSMA by immunostaining.


The sensitivity of 68Ga-PSMA PET/CT was notably better than that of MRI/CT and comparable to that of DW-MRI. Some false positive findings with DW-MRI reduced its specificity and positive predictive value compared with those of 68Ga-PSMA PET/CT and MRI/CT.


Anatomical cross-sectional imaging Diagnostic accuracy Prostatic neoplasm PSMA PET/CT Staging 


Author contributions

LJP, HDZ, NCL, UH, and JBNP contributed to the conception and design of the study; JBN, NCL, AP, DTA, and JC contributed to the acquisition of data; HDZ, AAO, RVF, NMDS, and KDP evaluated the imaging data; LJP, JBN, and HDZ performed the analysis/interpretation of data; LJP, JBN, and HDZ drafted the manuscript. All authors critically revised the manuscript and approved the final version of the manuscript.


The study was supported by an unrestricted Grant from the Obel Family Foundation (Grant no. 26063).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no competing interests.

Ethical approval

This clinical study was approved by the Danish Health and Medicine Authority, the Danish Data Protection Agency, and the Northern Denmark Region Committee in Health Research Ethics (N-20140079). The protocol was registered in the EudraCT database (#2014-004210-28).

Consent to participate

All patients received written and oral information and provided written informed consent.


  1. 1.
    Mottet N, Bellmunt J, Bolla M, Briers E, Cumberbatch MG, De Santis M, Fossati N, Gross T, Henry AM, Joniau S, Lam TB, Mason MD, Matveev VB, Moldovan PC, van den Bergh RC, Van den Broeck T, van der Poel HG, van der Kwast TH, Rouviere O, Schoots IG, Wiegel T, Cornford P (2017) EAU-ESTRO-SIOG guidelines on prostate cancer. Part 1: screening, diagnosis, and local treatment with curative intent. Eur Urol 71(4):618–629. Google Scholar
  2. 2.
    Carroll PH, Mohler JL (2018) NCCN guidelines updates: prostate cancer and prostate cancer early detection. J Natl Compr Cancer Netw 16(5s):620–623. Google Scholar
  3. 3.
    Sanda MG, Cadeddu JA, Kirkby E, Chen RC, Crispino T, Fontanarosa J, Freedland SJ, Greene K, Klotz LH, Makarov DV, Nelson JB, Rodrigues G, Sandler HM, Taplin ME, Treadwell JR (2018) Clinically localized prostate cancer: AUA/ASTRO/SUO guideline. Part II: recommended approaches and details of specific care options. J Urol 199(4):990–997. Google Scholar
  4. 4.
    Hovels AM, Heesakkers RA, Adang EM, Jager GJ, Strum S, Hoogeveen YL, Severens JL, Barentsz JO (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(4):387–395. Google Scholar
  5. 5.
    Eiber M, Maurer T, Souvatzoglou M, Beer AJ, Ruffani A, Haller B, Graner FP, Kubler H, Haberhorn U, Eisenhut M, Wester HJ, Gschwend JE, Schwaiger M (2015) Evaluation of hybrid 68Ga-PSMA ligand PET/CT in 248 patients with biochemical recurrence after radical prostatectomy. J Nucl Med 56(5):668–674. Google Scholar
  6. 6.
    Afshar-Oromieh A, Holland-Letz T, Giesel FL, Kratochwil C, Mier W, Haufe S, Debus N, Eder M, Eisenhut M, Schafer M, Neels O, Hohenfellner M, Kopka K, Kauczor HU, Debus J, Haberkorn U (2017) Diagnostic performance of 68Ga-PSMA-11 (HBED-CC) PET/CT in patients with recurrent prostate cancer: evaluation in 1007 patients. Eur J Nucl Med Mol Imaging 44(8):1258–1268. Google Scholar
  7. 7.
    Fendler WP, Calais J, Eiber M, Flavell RR, Mishoe A, Feng FY, Nguyen HG, Reiter RE, Rettig MB, Okamoto S, Emmett L, Zacho HD, Ilhan H, Wetter A, Rischpler C, Schoder H, Burger IA, Gartmann J, Smith R, Small EJ, Slavik R, Carroll PR, Herrmann K, Czernin J, Hope TA (2019) Assessment of 68Ga-PSMA-11 PET accuracy in localizing recurrent prostate cancer: a prospective single-arm clinical trial. JAMA Oncol. Google Scholar
  8. 8.
    Hope TA, Goodman JZ, Allen IE, Calais J, Fendler WP, Carroll PR (2018) Meta-analysis of 68Ga-PSMA-11 PET accuracy for the detection of prostate cancer validated by histopathology. J Nucl Med. Google Scholar
  9. 9.
    Perera M, Papa N, Roberts M, Williams M, Udovicich C, Vela I, Christidis D, Bolton D, Hofman MS, Lawrentschuk N, Murphy DG (2019) Gallium-68 prostate-specific membrane antigen positron emission tomography in advanced prostate cancer-updated diagnostic utility, sensitivity, specificity, and distribution of prostate-specific membrane antigen-avid lesions: a systematic review and meta-analysis. Eur Urol. Google Scholar
  10. 10.
    Petersen LJ, Zacho HD (2017) Gallium-68 prostate-specific membrane antigen positron emission tomography/computed tomography for staging of high-risk prostate cancer. Scand J Urol 51(6):498–501. Google Scholar
  11. 11.
    Bossuyt PM, Reitsma JB, Bruns DE, Gatsonis CA, Glasziou PP, Irwig LM, Lijmer JG, Moher D, Rennie D, de Vet HC, Standards for Reporting of Diagnostic A (2003) Towards complete and accurate reporting of studies of diagnostic accuracy: the STARD initiative. BMJ 326(7379):41–44Google Scholar
  12. 12.
    Zacho HD, Nielsen JB, Afshar-Oromieh A, Haberkorn U, deSouza N, De Paepe K, Dettmann K, Langkilde NC, Haarmark C, Fisker RV, Arp DT, Carl J, Jensen JB, Petersen LJ (2018) Prospective comparison of 68Ga-PSMA PET/CT, 18F-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 45(11):1884–1897. Google Scholar
  13. 13.
    Barentsz JO, Richenberg J, Clements R, Choyke P, Verma S, Villeirs G, Rouviere O, Logager V, Fütterer JJ (2012) ESUR prostate MR guidelines 2012. Eur Radiol 22(4):746–757. Google Scholar
  14. 14.
    Fendler WP, Calais J, Allen-Auerbach M, Bluemel C, Eberhardt N, Emmett L, Gupta P, Hartenbach M, Hope TA, Okamoto S, Pfob CH, Poppel TD, Rischpler C, Schwarzenbock S, Stebner V, Unterrainer M, Zacho HD, Maurer T, Gratzke C, Crispin A, Czernin J, Herrmann K, Eiber M (2017) 68Ga-PSMA-11 PET/CT interobserver agreement for prostate cancer assessments: an international multicenter prospective study. J Nucl Med 58(10):1617–1623. Google Scholar
  15. 15.
    Lecouvet FE, Oprea-Lager DE, Liu Y, Ost P, Bidaut L, Collette L, Deroose CM, Goffin K, Herrmann K, Hoekstra OS, Kramer G, Lievens Y, Lopci E, Pasquier D, Petersen LJ, Talbot JN, Zacho H, Tombal B, deSouza NM (2018) Use of modern imaging methods to facilitate trials of metastasis-directed therapy for oligometastatic disease in prostate cancer: a consensus recommendation from the EORTC Imaging Group. Lancet Oncol 19(10):e534–e545. Google Scholar
  16. 16.
    Rauscher I, Maurer T, Fendler WP, Sommer WH, Schwaiger M, Eiber M (2016) 68Ga-PSMA ligand PET/CT in patients with prostate cancer: how we review and report. Cancer Imaging 16(1):14. Google Scholar
  17. 17.
    Padhani AR, Lecouvet FE, Tunariu N, Koh DM, De Keyzer F, Collins DJ, Sala E, Schlemmer HP, Petralia G, Vargas HA, Fanti S, Tombal HB, de Bono J (2017) METastasis reporting and data system for prostate cancer: practical guidelines for acquisition, interpretation, and reporting of whole-body magnetic resonance imaging-based evaluations of multiorgan involvement in advanced prostate cancer. Eur Urol 71(1):81–92. Google Scholar
  18. 18.
    Nielsen JB, Zacho HD, Haberkorn U, Nielsen KM, Dettmann K, Langkilde NC, Petersen LJ (2017) A comprehensive safety evaluation of 68 Ga-labeled ligand prostate-specific membrane antigen 11 PET/CT in prostate cancer: the results of 2 prospective, multicenter trials. Clin Nucl Med 42(7):520–524. Google Scholar
  19. 19.
    Borley N, Fabrin K, Sriprasad S, Mondaini N, Thompson P, Muir G, Poulsen J (2003) Laparoscopic pelvic lymph node dissection allows significantly more accurate staging in “high-risk” prostate cancer compared to MRI or CT. Scand J Urol Nephrol 37(5):382–386. Google Scholar
  20. 20.
    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. Google Scholar
  21. 21.
    Budaus L, Leyh-Bannurah SR, Salomon G, Michl U, Heinzer H, Huland H, Graefen M, Steuber T, Rosenbaum C (2016) Initial experience of 68Ga-PSMA PET/CT imaging in high-risk prostate cancer patients prior to radical prostatectomy. Eur Urol 69(3):393–396. Google Scholar
  22. 22.
    Gupta M, Choudhury PS, Hazarika D, Rawal S (2017) A comparative study of 68Gallium-prostate specific membrane antigen positron emission tomography–computed tomography and magnetic resonance imaging for lymph node staging in high risk prostate cancer patients: an initial experience. World J Nucl Med 16(3):186–191. Google Scholar
  23. 23.
    Zhang Q, Zang S, Zhang C, Fu Y, Lv X, Zhang Q, Deng Y, Zhang C, Luo R, Zhao X, Wang W, Wang F, Guo H (2017) Comparison of 68Ga-PSMA-11 PET-CT with mpMRI for preoperative lymph node staging in patients with intermediate to high-risk prostate cancer. J Transl Med 15(1):230. Google Scholar
  24. 24.
    Yaxley JW, Raveenthiran S, Nouhaud FX, Samartunga H, Yaxley AJ, Coughlin G, Delahunt B, Egevad L, McEwan L, Wong D (2019) Outcomes of primary lymph node staging of intermediate and high risk prostate cancer with 68Ga-PSMA positron emission tomography/computerized tomography compared to histological correlation of pelvic lymph node pathology. J Urol 201(4):815–820. Google Scholar
  25. 25.
    Maurer T, Gschwend JE, Rauscher I, Souvatzoglou M, Haller B, Weirich G, Wester HJ, Heck M, Kubler H, Beer AJ, Schwaiger M, Eiber M (2016) Diagnostic efficacy of 68Gallium-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 195(5):1436–1443. Google Scholar
  26. 26.
    Obek C, Doganca T, Demirci E, Ocak M, Kural AR, Yildirim A, Yucetas U, Demirdag C, Erdogan SM, Kabasakal L, Members of Urooncology Association T (2017) The accuracy of 68Ga-PSMA PET/CT in primary lymph node staging in high-risk prostate cancer. Eur J Nucl Med Mol Imaging 44(11):1806–1812. Google Scholar
  27. 27.
    Van den Bergh L, Lerut E, Haustermans K, Deroose CM, Oyen R, Isebaert S, Budiharto T, Ameye F, Mottaghy FM, Bogaerts K, Van Poppel H, Joniau S (2015) 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 33(3):109. Google Scholar
  28. 28.
    Park SY, Zacharias C, Harrison C, Fan RE, Kunder C, Hatami N, Giesel F, Ghanouni P, Daniel B, Loening AM, Sonn GA, Iagaru A (2018) Gallium 68 PSMA-11 PET/MR imaging in patients with intermediate- or high-risk prostate cancer. Radiology 288(2):495–505. Google Scholar
  29. 29.
    Thoeny HC, Froehlich JM, Triantafyllou M, Huesler J, Bains LJ, Vermathen P, Fleischmann A, Studer UE (2014) Metastases in normal-sized pelvic lymph nodes: detection with diffusion-weighted MR imaging. Radiology 273(1):125–135. Google Scholar
  30. 30.
    van Leeuwen PJ, Emmett L, Ho B, Delprado W, Ting F, Nguyen Q, Stricker PD (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(2):209–215. Google Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Lars J. Petersen
    • 1
    • 2
    Email author
  • Julie B. Nielsen
    • 1
    • 2
  • Niels C. Langkilde
    • 2
    • 3
  • Astrid Petersen
    • 4
  • Ali Afshar-Oromieh
    • 5
  • Nandita M. De Souza
    • 6
  • Katja De Paepe
    • 6
  • Rune V. Fisker
    • 1
    • 7
  • Dennis T. Arp
    • 8
  • Jesper Carl
    • 8
    • 9
  • Uwe Haberkorn
    • 10
    • 11
  • Helle D. Zacho
    • 1
    • 2
  1. 1.Department of Nuclear MedicineAalborg University HospitalAalborgDenmark
  2. 2.Department of Clinical MedicineAalborg UniversityAalborgDenmark
  3. 3.Department of UrologyAalborg University HospitalAalborgDenmark
  4. 4.Department of PathologyAalborg University HospitalAalborgDenmark
  5. 5.Department of Nuclear MedicineBern University HospitalBernSwitzerland
  6. 6.The Institute of Cancer Research and Royal Marsden NHS Foundation TrustLondonUK
  7. 7.Department of RadiologyAalborg University HospitalAalborgDenmark
  8. 8.Department of Medical PhysicsAalborg University HospitalAalborgDenmark
  9. 9.Department of OncologyNaestved Sygehus, Zealand University HospitalNaestvedDenmark
  10. 10.Department of Nuclear MedicineUniversity Hospital HeidelbergHeidelbergGermany
  11. 11.Clinical Cooperation Unit Nuclear MedicineDKFZHeidelbergGermany

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