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68Ga-PSMA-11 PET has the potential to improve patient selection for extended pelvic lymph node dissection in intermediate to high-risk prostate cancer

  • Daniela A. Ferraro
  • Urs J. Muehlematter
  • Helena I. Garcia Schüler
  • Niels J. Rupp
  • Martin Huellner
  • Michael Messerli
  • Jan Hendrik Rüschoff
  • Edwin E. G. W. ter Voert
  • Thomas Hermanns
  • Irene A. BurgerEmail author
Original Article
Part of the following topical collections:
  1. Oncology – Genitourinary

Abstract

Introduction

Radical prostatectomy with extended pelvic lymph node dissection (ePLND) is a curative treatment option for patients with clinically significant localised prostate cancer. The decision to perform an ePLND can be challenging because the overall incidence of lymph node metastasis is relatively low and ePLND is not free of complications. Using current clinical nomograms to identify patients with nodal involvement, approximately 75–85% of ePLNDs performed are negative. The aim of this study was to assess the added value of 68Ga-PSMA-11 PET in predicting lymph node metastasis in men with intermediate- or high-risk prostate cancer.

Methods

68Ga-PSMA-11 PET scans of 60 patients undergoing radical prostatectomy with ePLND were reviewed for qualitative (visual) assessment of suspicious nodes and assessment of quantitative parameters of the primary tumour in the prostate (SUVmax, total activity (PSMAtotal) and PSMA positive volume (PSMAvol)). Ability of quantitative PET parameters to predict nodal metastasis was assessed with receiver operating characteristics (ROC) analysis. A multivariable logistic regression model combining PSA, Gleason score, visual nodal status on PET and primary tumour PSMAtotal was built. Net benefit at each risk threshold was compared with five nomograms: MSKCC nomogram, Yale formula, Roach formula, Winter nomogram and Partin tables (2016).

Results

Overall, pathology of ePLND specimens revealed 31 pelvic metastatic lymph nodes in 12 patients. 68Ga-PSMA-11 PET visual analysis correctly detected suspicious nodes in 7 patients, yielding a sensitivity of 58% and a specificity of 98%. The area under the ROC curve for primary tumour SUVmax was 0.70, for PSMAtotal 0.76 and for PSMAvol 0.75. The optimal cut-off for nodal involvement was PSMAtotal > 49.1. The PET model including PSA, Gleason score and quantitative PET parameters had a persistently higher net benefit compared with all clinical nomograms.

Conclusion

Our model combining PSA, Gleason score and visual lymph node analysis on 68Ga-PSMA-11 PET with PSMAtotal of the primary tumour showed a tendency to improve patient selection for ePLND over the currently used clinical nomograms. Although this result has to be validated, 68Ga-PSMA-11 PET showed the potential to reduce unnecessary surgical procedures in patients with intermediate- or high-risk prostate cancer.

Keywords

SUVmax PET quantification Lymph node metastases PET/MR PET/CT Staging Prediction model Nomogram Net benefit 

Abbreviations

RPE

Radical prostatectomy

ePLND

Extended pelvic lymph node dissection

RT

Radiotherapy

LNM

Lymph node metastasis

CT

Computed tomography

PET

Positron emission tomography

68Ga-PSMA-11 PET

Positron emission tomography with prostate-specific membrane antigen

68Ga-PSMA-11 PET/MRI

68Ga-PSMA-11 PET/magnetic resonance imaging

PSA

Prostate-specific antigen

GS

Gleason score

MSKCC

MSKCC nomogram

YF

Yale formula

RF

Roach formula

WN

Winter nomogram

PT (2016)

Partin tables

SD

Standard deviation

SUVmax

Standard uptake value

PSMAvol

PSMA positive volume

PSMAtotal

PSMA accumulation

ROC

Receiver operating characteristics

AUC

Area under the ROC curve

NB

Net benefit

EIP

Irradiation of the pelvic nodes

CI

95% Confidence interval

Notes

Acknowledgements

The authors acknowledge the technicians Marlena Hofbauer and Josephine Trinckauf and their team for the excellent work on high-quality PET images.

Authors’ contributions

DAF—data collection, data analysis and manuscript writing.

UJM—data analysis, statistics and manuscript writing.

HIGS and TH—patient selection, manuscript writing.

NJR, EEGWV, MM, JHR and MH—manuscript editing and revision.

IAB—study design and manuscript writing.

All authors reviewed and agreed to the manuscript content.

Funding information

The Department of Nuclear Medicine holds an institutional Research Contract with GE Healthcare. This study was financially supported by the Sick legat and the Iten-Kohaut foundation

Compliance with ethical standards

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.

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.

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. MH received an Investigator-Initiated Study grant from GE Healthcare. MM received speaker fees from GE Healthcare. Authors DAF, UJM, HIGS, NJR, JHR and EEGWV declare no conflict of interest.

Supplementary material

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ESM 1

(PNG 182 kb)

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High resolution image (TIFF 4069 kb)

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Copyright information

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

Authors and Affiliations

  • Daniela A. Ferraro
    • 1
  • Urs J. Muehlematter
    • 1
    • 2
  • Helena I. Garcia Schüler
    • 3
  • Niels J. Rupp
    • 4
  • Martin Huellner
    • 1
  • Michael Messerli
    • 1
  • Jan Hendrik Rüschoff
    • 4
  • Edwin E. G. W. ter Voert
    • 1
  • Thomas Hermanns
    • 5
  • Irene A. Burger
    • 1
    • 6
    Email author
  1. 1.Department of Nuclear MedicineUniversity Hospital Zurich, University of ZurichZürichSwitzerland
  2. 2.Institute of Diagnostic and Interventional RadiologyUniversity Hospital Zurich, University of ZurichZurichSwitzerland
  3. 3.Department of Radiation OncologyUniversity Hospital Zurich, University of ZurichZurichSwitzerland
  4. 4.Department of Pathology and Molecular PathologyUniversity Hospital Zurich, University of ZurichZurichSwitzerland
  5. 5.Department of UrologyUniversity Hospital Zurich, University of ZurichZurichSwitzerland
  6. 6.Department of Nuclear MedicineKantonsspital BadenBadenSwitzerland

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