title: Comparison of68Ga-HBED-CC PSMA-PET/CT and multiparametric MRI for gross tumour volume detection in patients with primary prostate cancer based on slice by slice comparison with histopathology.
abstract: The exact detection and delineation of the intraprostatic tumour burden is crucial for treatment planning in primary prostate cancer (PCa). We compared68Ga-HBED-CC-PSMA PET/CT with multiparametric MRI (mpMRI) for diagnosis and tumour delineation in patients with primary PCa based on slice by slice correlation with histopathological reference material.
  
  
  
  Seven patients with histopathologically proven primary PCa underwent68Ga-HBED-CC-PSMA PET/CT and MRI followed by radical prostatectomy. Resected prostates were scanned by ex-vivo CT in a special localizer and prepared for histopathology. Invasive PCa was delineated on a HE stained histologic tissue slide and matched to ex-vivo CT to obtain gross tumor volume (GTV-)histo. Ex-vivo CT including GTV-histo and MRI data were matched to in-vivo CT(PET). Consensus contours based on MRI (GTV-MRI), PSMA PET (GTV-PET) or the combination of both (GTV-union/-intersection) were created. In each in-vivo CT slice the prostate was separated into 4 equal segments and sensitivity and specificity for PSMA PET and mpMRI were assessed by comparison with histological reference material. Furthermore, the spatial overlap between GTV-histo and GTV-PET/-MRI and the Sørensen-Dice coefficient (DSC) were calculated. In the case of multifocal PCa (4/7 patients), SUV values (PSMA PET) and ADC-values (diffusion weighted MRI) were obtained for each lesion.
  
  
  
  PSMA PET and mpMRI detected PCa in all patients. GTV-histo was detected in 225 of 340 segments (66.2%). Sensitivity and specificity for GTV-PET, GTV-MRI, GTV-union and GTV-intersection were 75% and 87%, 70% and 82%, 82% and 67%, 55% and 99%, respectively. GTV-histo had on average the highest overlap with GTV-union (57±22%), which was significantly higher than overlap with GTV-MRI (p=0.016) and GTV-PET (p=0.016), respectively. The mean DSC for GTV-union, GTV-PET and GTV-MRI was 0.51 (±0.18), 0.45 (±0.17) and 0.48 (±0.19), respectively. In every patient with multifocal PCa there was one lesion which had both the highest SUV and the lowest ADC-value (mean and max).
  
  
  
  In a slice by slice analysis with histopathology,68Ga-HBED-CC-PSMA PET/CT and mpMRI showed high sensitivity and specificity in detection of primary PCa. A combination of both methods performed even better in terms of sensitivity (GTV-union) and specificity (GTV-intersection). A moderate to good spatial overlap with GTV-histo was observed for PSMA PET/CT and mpMRI alone which was significantly improved by GTV-union. Further studies are warranted to analyse the impact of these preliminary findings for diagnostic (multimodal guided TRUS biopsy) and therapeutic (focal therapy) strategies in primary PCa.
authors.affiliation: Department of Radiation Oncology, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Germany; German Cancer Consortium (DKTK), Partner Site Freiburg, Germany.
authors.forename: Constantinos
authors.initials: C
authors.lastname: Zamboglou
authors.affiliation: Department of Pathology, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Germany; German Cancer Consortium (DKTK), Partner Site Freiburg, Germany.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Drendel
authors.affiliation: Department of Urology, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Germany; German Cancer Consortium (DKTK), Partner Site Freiburg, Germany.
authors.forename: Cordula A
authors.initials: CA
authors.lastname: Jilg
authors.affiliation: Department of Radiation Oncology, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Germany; German Cancer Consortium (DKTK), Partner Site Freiburg, Germany.
authors.forename: Hans C
authors.initials: HC
authors.lastname: Rischke
authors.affiliation: Department of Nuclear Medicine, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Germany; German Cancer Consortium (DKTK), Partner Site Freiburg, Germany.
authors.forename: Teresa I
authors.initials: TI
authors.lastname: Beck
authors.affiliation: Department of Urology, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Germany; German Cancer Consortium (DKTK), Partner Site Freiburg, Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Schultze-Seemann
authors.affiliation: Department of Radiology, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Germany; German Cancer Consortium (DKTK), Partner Site Freiburg, Germany.
authors.forename: Tobias
authors.initials: T
authors.lastname: Krauss
authors.affiliation: Department of Nuclear Medicine, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Germany; German Cancer Consortium (DKTK), Partner Site Freiburg, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Mix
authors.affiliation: Department of Nuclear Medicine, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Germany; German Cancer Consortium (DKTK), Partner Site Freiburg, Germany.
authors.forename: Florian
authors.initials: F
authors.lastname: Schiller
authors.affiliation: Department of Urology, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Germany; German Cancer Consortium (DKTK), Partner Site Freiburg, Germany.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Wetterauer
authors.affiliation: Department of Pathology, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Germany; German Cancer Consortium (DKTK), Partner Site Freiburg, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Werner
authors.affiliation: Department of Radiology, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Germany; German Cancer Consortium (DKTK), Partner Site Freiburg, Germany.
authors.forename: Mathias
authors.initials: M
authors.lastname: Langer
authors.affiliation: Department of Radiology, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Germany; German Cancer Consortium (DKTK), Partner Site Freiburg, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Bock
authors.affiliation: Department of Nuclear Medicine, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Germany; German Cancer Consortium (DKTK), Partner Site Freiburg, Germany.
authors.forename: Philipp T
authors.initials: PT
authors.lastname: Meyer
authors.affiliation: Department of Radiation Oncology, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Germany; German Cancer Consortium (DKTK), Partner Site Freiburg, Germany.
authors.forename: Anca L
authors.initials: AL
authors.lastname: Grosu
mesh_terms: D000954:Antigens, Surface / Q000032:analysis* / Q000378:metabolism; D004492:Edetic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000378:metabolism; D043425:Glutamate Carboxypeptidase II / Q000032:analysis* / Q000378:metabolism; D006651:Histocytochemistry; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D000072078:Positron Emission Tomography Computed Tomography / Q000379:methods*; D011471:Prostatic Neoplasms / Q000000981:diagnostic imaging* / Q000473:pathology*; D012680:Sensitivity and Specificity; D047368:Tumor Burden
chemical_list: D000954:Antigens, Surface; C075313:N,N'-bis(2-hydroxy-5-(ethylene-beta-carboxy)benzyl)ethylenediamine N,N'-diacetic acid; D004492:Edetic Acid; C473848:FOLH1 protein, human; D043425:Glutamate Carboxypeptidase II
keywords: PSMA PET/CT; Prostate cancer; histopathology.; multiparametric MRI