Wojciech Cytawa1,2, Stefan Kircher3, Hubert Kübler4, Rudolf A Werner5, Simon Weber5, Philipp Hartrampf5, Tomasz Bandurski6, Piotr Lass7, Wojciech Połom8, Marcin Matuszewski8, Hans-Jürgen Wester9, Constantin Lapa10, Andreas Rosenwald3, Anna Katharina Seitz4, Andreas K Buck5. 1. Department of Nuclear Medicine, University Hospital Würzburg, Würzburg, Germany. wcytawa@gumed.edu.pl. 2. Department of Nuclear Medicine, Medical University of Gdańsk, Smoluchowskiego Str. 17, 80-952, Gdańsk, Poland. wcytawa@gumed.edu.pl. 3. Institute of Pathology, Comprehensive Cancer Center Mainfranken (CCCMF), University of Würzburg, Würzburg, Germany. 4. Department of Urology, University Hospital Würzburg, Würzburg, Germany. 5. Department of Nuclear Medicine, University Hospital Würzburg, Würzburg, Germany. 6. Department of Radiology Informatics and Statistics, Medical University of Gdańsk, Gdańsk, Poland. 7. Department of Nuclear Medicine, Medical University of Gdańsk, Smoluchowskiego Str. 17, 80-952, Gdańsk, Poland. 8. Department of Urology, Medical University of Gdansk, Gdańsk, Poland. 9. Pharmaceutical Radiochemistry, Technische Universität München, Munich, Germany. 10. Nuclear Medicine, Medical Faculty, University of Augsburg, Augsburg, Germany.
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.
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.
Authors: Ali Afshar-Oromieh; John W Babich; Clemens Kratochwil; Frederik L Giesel; Michael Eisenhut; Klaus Kopka; Uwe Haberkorn Journal: J Nucl Med Date: 2016-10 Impact factor: 10.057
Authors: A V D'Amico; R Whittington; S B Malkowicz; D Schultz; K Blank; G A Broderick; J E Tomaszewski; A A Renshaw; I Kaplan; C J Beard; A Wein Journal: JAMA Date: 1998-09-16 Impact factor: 56.272
Authors: A Afshar-Oromieh; A Malcher; M Eder; M Eisenhut; H G Linhart; B A Hadaschik; T Holland-Letz; F L Giesel; C Kratochwil; S Haufe; U Haberkorn; C M Zechmann Journal: Eur J Nucl Med Mol Imaging Date: 2012-11-24 Impact factor: 9.236
Authors: Sara Sheikhbahaei; Ali Afshar-Oromieh; Matthias Eiber; Lilja B Solnes; Mehrbod S Javadi; Ashley E Ross; Kenneth J Pienta; Mohamad E Allaf; Uwe Haberkorn; Martin G Pomper; Michael A Gorin; Steven P Rowe Journal: Eur J Nucl Med Mol Imaging Date: 2017-08-01 Impact factor: 9.236
Authors: Wojciech Cytawa; Anna Katharina Seitz; Stefan Kircher; Kazuhito Fukushima; Johannes Tran-Gia; Andreas Schirbel; Tomasz Bandurski; Piotr Lass; Markus Krebs; Wojciech Połom; Marcin Matuszewski; Hans-Jürgen Wester; Andreas K Buck; Hubert Kübler; Constantin Lapa Journal: Eur J Nucl Med Mol Imaging Date: 2019-09-16 Impact factor: 9.236