Zamboglou Constantinos, Drendel Vanessa, Jilg Cordula A, Rischke Hans C, Beck Teresa I, Schultze-Seemann Wolfgang, Krauss Tobias, Mix Michael, Schiller Florian, Wetterauer Ulrich, Werner Martin, Langer Mathias, Bock Michael, Meyer Philipp T, Grosu Anca L
Department of Radiation Oncology, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Germany; German Cancer Consortium (DKTK), Partner Site Freiburg, Germany.
Department of Pathology, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Germany; German Cancer Consortium (DKTK), Partner Site Freiburg, Germany.
Theranostics. 2017 Jan 1;7(1):228-237. doi: 10.7150/thno.16638. eCollection 2017.
The exact detection and delineation of the intraprostatic tumour burden is crucial for treatment planning in primary prostate cancer (PCa). We compared Ga-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 underwent Ga-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, Ga-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.
准确检测和描绘前列腺内肿瘤负荷对于原发性前列腺癌（PCa）的治疗规划至关重要。我们基于与组织病理学参考材料的逐片相关性，比较了Ga-HBED-CC-PSMA PET/CT与多参数MRI（mpMRI）在原发性PCa患者中的诊断和肿瘤描绘情况。
7例经组织病理学证实的原发性PCa患者接受了Ga-HBED-CC-PSMA PET/CT和MRI检查，随后进行了根治性前列腺切除术。切除的前列腺在特殊定位器中进行离体CT扫描，并准备进行组织病理学检查。在苏木精-伊红染色的组织切片上描绘浸润性PCa，并与离体CT匹配以获得大体肿瘤体积（GTV-histo）。将包括GTV-histo和MRI数据的离体CT与活体CT（PET）匹配。基于MRI（GTV-MRI）、PSMA PET（GTV-PET）或两者结合（GTV-union/-intersection）创建共识轮廓。在每个活体CT切片中，将前列腺分为4个相等的部分，并通过与组织学参考材料比较评估PSMA PET和mpMRI的敏感性和特异性。此外，计算GTV-histo与GTV-PET/-MRI之间的空间重叠以及 Sørensen-Dice系数（DSC）。对于多灶性PCa患者（4/7例），获取每个病灶的SUV值（PSMA PET）和ADC值（扩散加权MRI）。
PSMA PET和mpMRI在所有患者中均检测到PCa。在340个部分中的225个（66.2%）检测到GTV-histo。GTV-PET、GTV-MRI、GTV-union和GTV-intersection的敏感性和特异性分别为75%和87%、70%和82%、82%和67%、55%和99%。GTV-histo与GTV-union的平均重叠率最高（57±22%），分别显著高于与GTV-MRI（p = 0.016）和GTV-PET（p = 0.016）的重叠率。GTV-union、GTV-PET和GTV-MRI的平均DSC分别为0.51（±0.18）、0.45（±0.17）和0.48（±0.19）。在每例多灶性PCa患者中，均有一个病灶的SUV最高且ADC值最低（平均值和最大值）。
在与组织病理学的逐片分析中，Ga-HBED-CC-PSMA PET/CT和mpMRI在检测原发性PCa方面显示出高敏感性和特异性。两种方法的结合在敏感性（GTV-union）和特异性（GTV-intersection）方面表现更佳。单独的PSMA PET/CT和mpMRI与GTV-histo有中度至良好的空间重叠，GTV-union显著改善了这种重叠。有必要进行进一步研究，以分析这些初步结果对原发性PCa诊断（多模态引导TRUS活检）和治疗（聚焦治疗）策略的影响。
