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Diverse PSMA expression in primary prostate cancer: reason for negative [68Ga]Ga-PSMA PET/CT scans? Immunohistochemical validation in 40 surgical specimens

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European Journal of Nuclear Medicine and Molecular Imaging Aims and scope Submit manuscript

Abstract

Purpose

The purpose of this study was to immunohistochemically validate the primary tumor PSMA expression in prostate cancer (PCa) patients imaged with [68Ga]Ga-PSMA PET/CT prior to surgery, with special consideration of PET-negative cases.

Methods

The study included 40 men with newly diagnosed treatment-naïve PCa imaged with [68Ga]Ga-PSMA I&T PET/CT as part of the diagnostic work-up prior to radical prostatectomy. All primary tumors were routinely stained with H&E. In addition, immunohistochemical staining of PSMA was performed and the immunoreactive score (IRS) was computed as semiquantitative measure. Subsequently, imaging findings were correlated to histopathologic results.

Results

Eighty-three percent (33/40) of patients presented focal uptake of [68Ga]Ga-PSMA I&T in the primary tumor in at least one prostate lobe. Among PSMA-PET positive patients, one-third had lymph node metastases (LNM) detected by post-operative histopathology, while in PET negative patients, only 1 out of 7 presented with regional LN involvement; PSMA-avid distant lesions, predominantly in bones, were observed in 15% and 0% of patients, respectively.

The median IRS classification of PSMA expression in tumor tissue was 2 (range, 1–3) both in PSMA-PET positive and negative prostate lobes, with significantly different interquartile range: 2–3 vs. 2–2, respectively (p = 0.03). The median volume of PSMA-PET positive tumors was 5.4 mL (0.2–32.9) as compared to 1.6 mL (0.3–18.3) of PET-negative tumors (p < 0.001). There was a significant but weak correlation between SUVmax and percentage of PSMA-positive tumor cells (r = 0.46, p < 0.001). A total of 35/44 (~80%) lobes were positive in PSMA-PET imaging, when a cut-off percentage of PSMA-positive cells was ≥ 90%, while 19/36 (~53%) lobes with < 90% PSMA-positive cells were PSMA-PET negative.

Conclusion

Positive [68Ga]Ga-PSMA I&T PET/CT scan of primary tumor of PCa results from a combination of factors, such as homogeneity and intensity of PSMA expression, tumor volume and grade, with a cutoff value of ≥ 90% PSMA-positive cells strongly determining PET-positivity. Focal accumulation of [68Ga]Ga-PSMA in the primary tumor may correlate positively with aggressiveness of prostate cancer, harboring higher risk of regional LN involvement and distant metastatic spread.

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Data availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Author notes

    Authors and Affiliations

    1. Department of Nuclear Medicine, University Hospital Würzburg, Würzburg, Germany

      Wojciech Cytawa, Rudolf A. Werner, Simon Weber, Philipp Hartrampf & Andreas K. Buck

    2. Department of Nuclear Medicine, Medical University of Gdańsk, Smoluchowskiego Str. 17, 80-952, Gdańsk, Poland

      Wojciech Cytawa & Piotr Lass

    3. Institute of Pathology, Comprehensive Cancer Center Mainfranken (CCCMF), University of Würzburg, Würzburg, Germany

      Stefan Kircher & Andreas Rosenwald

    4. Department of Urology, University Hospital Würzburg, Würzburg, Germany

      Hubert Kübler & Anna Katharina Seitz

    5. Department of Radiology Informatics and Statistics, Medical University of Gdańsk, Gdańsk, Poland

      Tomasz Bandurski

    6. Department of Urology, Medical University of Gdansk, Gdańsk, Poland

      Wojciech Połom & Marcin Matuszewski

    7. Pharmaceutical Radiochemistry, Technische Universität München, Munich, Germany

      Hans-Jürgen Wester

    8. Nuclear Medicine, Medical Faculty, University of Augsburg, Augsburg, Germany

      Constantin Lapa

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    1. Wojciech Cytawa
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    Contributions

    Andreas K. Buck contributed to the study conception and design. Material preparation, data collection, and analysis were performed by Wojciech Cytawa, Stefan Kircher, Simon Weber, Philipp Hartrampf, Tomasz Bandurski, Constantin Lapa, and Anna Katharina Seitz. The first draft of the manuscript was written by Wojciech Cytawa. Writing — review and editing were performed by Wojciech Cytawa, Stefan Kircher, Constantin Lapa, Anna Katharina Seitz, and Andreas K. Buck. All authors read the manuscript, commented on it, and approved its final version.

    Corresponding author

    Correspondence to Wojciech Cytawa.

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    Ethics approval

    All procedures involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

    Consent to participate

    Informed consent was obtained from all individual participants included in the study.

    Conflict of interest

    Hans-Jürgen Wester is the founder and shareholder of Scintomics. All other authors have no relevant financial or non-financial interests to disclose.

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    This article is part of the Topical Collection on Oncology - Genitourinary

    Wojciech Cytawa and Stefan Kircher contributed equally to the manuscript. Anna Katharina Seitz and Andreas K. Buck shared the last authorship.

    Piotr Lass is deceased.

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    Cytawa, W., Kircher, S., Kübler, H. et al. Diverse PSMA expression in primary prostate cancer: reason for negative [68Ga]Ga-PSMA PET/CT scans? Immunohistochemical validation in 40 surgical specimens. Eur J Nucl Med Mol Imaging 49, 3938–3949 (2022). https://doi.org/10.1007/s00259-022-05831-8

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