What's behind 68Ga-PSMA-11 uptake in primary prostate cancer PET? Investigation of histopathological parameters and immunohistochemical PSMA expression patterns

Jan H Rüschoff; Daniela A Ferraro; Urs J Muehlematter; Riccardo Laudicella; Thomas Hermanns; Ann-Katrin Rodewald; Holger Moch; Daniel Eberli; Irene A Burger; Niels J Rupp

doi:10.1007/s00259-021-05501-1

What's behind ⁶⁸Ga-PSMA-11 uptake in primary prostate cancer PET? Investigation of histopathological parameters and immunohistochemical PSMA expression patterns

Eur J Nucl Med Mol Imaging. 2021 Nov;48(12):4042-4053. doi: 10.1007/s00259-021-05501-1. Epub 2021 Aug 13.

Authors

Jan H Rüschoff^#¹, Daniela A Ferraro^#^{2

3}, Urs J Muehlematter², Riccardo Laudicella^{2

4}, Thomas Hermanns⁵, Ann-Katrin Rodewald¹, Holger Moch¹, Daniel Eberli⁵, Irene A Burger^#^{2

6}, Niels J Rupp^#⁷

Affiliations

¹ Department of Pathology and Molecular Pathology, University Hospital Zurich, University of Zurich, Zurich, Switzerland.
² Department of Nuclear Medicine, University Hospital Zurich, University of Zurich, Zurich, Switzerland.
³ Department of Radiology and Oncology, Faculdade de Medicina FMUSP, Universidade de Sao Paulo, Sao Paulo, Brazil.
⁴ Department of Biomedical and Dental Sciences and Morpho-Functional Imaging, Nuclear Medicine Unit, University of Messina, Messina, Italy.
⁵ Department of Urology, University Hospital Zurich, University of Zurich, Zurich, Switzerland.
⁶ Department of Nuclear Medicine, Kantonsspital Baden, Baden, Switzerland.
⁷ Department of Pathology and Molecular Pathology, University Hospital Zurich, University of Zurich, Zurich, Switzerland. niels.rupp@usz.ch.

^# Contributed equally.

Abstract

Purpose: Prostate-specific membrane antigen (PSMA-) PET has become a promising tool in staging and restaging of prostate carcinoma (PCa). However, specific primary tumour features might impact accuracy of PSMA-PET for PCa detection. We investigated histopathological parameters and immunohistochemical PSMA expression patterns on radical prostatectomy (RPE) specimens and correlated them to the corresponding ⁶⁸Ga-PSMA-11-PET examinations.

Methods: RPE specimens of 62 patients with preoperative ⁶⁸Ga-PSMA-11-PET between 2016 and 2018 were analysed. WHO/ISUP grade groups, growth pattern (expansive vs. infiltrative), tumour area and diameter as well as immunohistochemical PSMA heterogeneity, intensity and negative tumour area (PSMA_%neg) were correlated with spatially corresponding SUV_max on ⁶⁸Ga-PSMA-11-PET in a multidisciplinary analysis.

Results: All tumours showed medium to strong membranous (2-3 +) and weak to strong cytoplasmic (1-3 +) PSMA expression. Heterogeneously expressed PSMA was found in 38 cases (61%). Twenty-five cases (40%) showed at least 5% and up to 80% PSMA_%neg. PSMA_%neg, infiltrative growth pattern, smaller tumour area and diameter and WHO/ISUP grade group 2 significantly correlated with lower SUV_max values. A ROC curve analysis revealed 20% PSMA_%neg as an optimal cutoff with the highest sensitivity and specificity (89% and 86%, AUC 0.923) for a negative PSMA-PET scan. A multiple logistic regression model revealed tumoural PSMA_%neg (p < 0.01, OR = 9.629) and growth pattern (p = 0.0497, OR = 306.537) as significant predictors for a negative PSMA-PET scan.

Conclusions: We describe PSMA_%neg, infiltrative growth pattern, smaller tumour size and WHO/ISUP grade group 2 as parameters associated with a lower ⁶⁸Ga-PSMA-11 uptake in prostate cancer. These findings can serve as fundament for future biopsy-based biomarker development to enable an individualized, tumour-adapted imaging approach.

Keywords: Glutamate carboxypeptidase II; Immunohistochemistry; Neoplasm staging; Positron emission tomography; Prostatic neoplasms.

MeSH terms

Edetic Acid
Gallium Isotopes
Gallium Radioisotopes
Humans
Male
Oligopeptides
Positron Emission Tomography Computed Tomography*
Prostatic Neoplasms* / diagnostic imaging

Substances

Gallium Isotopes
Gallium Radioisotopes
Oligopeptides
gallium 68 PSMA-11
Edetic Acid