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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

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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.

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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

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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. This study was financially supported by the Sick legat and the Iten-Kohaut foundation

Author information

Authors and Affiliations

  1. Department of Nuclear Medicine, University Hospital Zurich, University of Zurich, Rämistrasse 100, 8091, Zürich, Switzerland

    Daniela A. Ferraro, Urs J. Muehlematter, Martin Huellner, Michael Messerli, Edwin E. G. W. ter Voert & Irene A. Burger

  2. Institute of Diagnostic and Interventional Radiology, University Hospital Zurich, University of Zurich, Zurich, Switzerland

    Urs J. Muehlematter

  3. Department of Radiation Oncology, University Hospital Zurich, University of Zurich, Zurich, Switzerland

    Helena I. Garcia Schüler

  4. Department of Pathology and Molecular Pathology, University Hospital Zurich, University of Zurich, Zurich, Switzerland

    Niels J. Rupp & Jan Hendrik Rüschoff

  5. Department of Urology, University Hospital Zurich, University of Zurich, Zurich, Switzerland

    Thomas Hermanns

  6. Department of Nuclear Medicine, Kantonsspital Baden, Baden, Switzerland

    Irene A. Burger

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  1. Daniela A. Ferraro
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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.

Corresponding author

Correspondence to Irene A. Burger.

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.

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.

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Daniela A Ferraro and Urs J. Muehlematter shared first authorship

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Ferraro, D.A., Muehlematter, U.J., Garcia Schüler, H.I. et al. 68Ga-PSMA-11 PET has the potential to improve patient selection for extended pelvic lymph node dissection in intermediate to high-risk prostate cancer. Eur J Nucl Med Mol Imaging 47, 147–159 (2020). https://doi.org/10.1007/s00259-019-04511-4

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