Abstract: Comparison studies using histopathology as standard of reference enable a validation of the diagnostic performance of imaging methods. This study analysed (1) the impact of different image-histopathology co-registration pathways, (2) the impact of the applied data analysis method and (3) intraindividually compared multiparametric magnet resonance tomography (mpMRI) and prostate specific membrane antigen positron emission tomography (PSMA-PET) by using the different approaches. Ten patients with primary PCa who underwent mpMRI and [18F]PSMA-1007 PET/CT followed by prostatectomy were prospectively enrolled. We demonstrate that the choice of the intermediate registration step [(1) via ex-vivo CT or (2) mpMRI] does not significantly affect the performance of the registration framework. Comparison of analysis methods revealed that methods using high spatial resolutions e.g. quadrant-based slice-by-slice analysis are beneficial for a differentiated analysis of performance, compared to methods with a lower resolution (segment-based analysis with 6 or 18 segments and lesions-based analysis). Furthermore, PSMA-PET outperformed mpMRI for intraprostatic PCa detection in terms of sensitivity (median %: 83-85 vs. 60-69, p

Abstract: Ex vivo studies have shown that the gastrin releasing peptide receptor (GRPr) is overexpressed on almost all primary prostate cancers, making it a promising target for prostate cancer imaging and targeted radiotherapy. Methods: Biodistribution, dosimetry and tumor uptake of the GRPr antagonist 64Cu-CB-TE2A-AR06 [(64Cu-4,11-bis(carboxymethyl)-1,4,8,11-tetraazabicyclo(6.6.2)hexadecane)-PEG4-D-Phe-Gln-Trp-Ala-Val-Gly-His-Sta-LeuNH2] were studied by PET/CT in four patients with newly diagnosed prostate cancer (T1c-T2b, Gleason 6-7). Results: No adverse events were observed after injection of 64Cu-CB-TE2A-AR06. Three of four tumors were visualized with high contrast [tumor-to-prostate ratio > 4 at 4 hours (h) post injection (p.i.)], one small tumor (T1c, 5% tumor on biopsy specimens) showed moderate contrast (tumor-to-prostate ratio at 4 h: 1.9). Radioactivity was cleared by the kidneys and only the pancreas demonstrated significant accumulation of radioactivity, which rapidly decreased over time.br

Abstract: Background We evaluated the influence of comorbidity inferred risks for lymph node metastasis (pN1) and positive surgical margins (R1) after radical prostatectomy in order to optimize pretherapeutic risk classification. We analyzed 454 patients after radical prostatectomy (RP) between 2009 and 2014. Comorbidities were defined by patients' medication from our electronic patient chart and stratified according to the ATC WHO code. Endpoints were lymph node metastasis (pN1) and positive surgical margins (R1). Results Rates for pN1 and R1 were 21.4% (97/454) and 29.3% (133/454), respectively. In addition to CAPRA and Gleason score, we identified diabetes as a significant medication inferred risk factor for pN1 (OR 2.9, p = 0.004/OR 3.2, p = 0.001/OR 3.5, p = 0.001) and beta-blockers for R1 (OR 1.9, p = 0.020/OR 2.9, p = 0.004). Patients with diabetes showed no statistically significant difference in Gleason score, CAPRA Score, PSA, and age compared to non-diabetic patients. Conclusions We identified diabetes and beta1 adrenergic blockage as significant risk factors for lymph node metastasis and positive surgical margins in prostate cancer (PCa). Patients at risk will need intensive pretherapeutic staging for optimal therapeutic stratification

Abstract: Purpose: Accurate contouring of intraprostatic gross tumor volume (GTV) is pivotal for successful delivery of focal therapies and for biopsy guidance in patients with primary prostate cancer (PCa). Contouring of GTVs, using 18-Fluor labeled tracer prostate specific membrane antigen positron emission tomography ([18F]PSMA-1007/PET) has not been examined yet. Patients and Methods: Ten Patients with primary PCa who underwent [18F]PSMA-1007 PET followed by radical prostatectomy were prospectively enrolled. Coregistered histopathological gross tumor volume (GTV-Histo) was used as standard of reference. PSMA-PET images were contoured on two ways: (1) manual contouring with PET scaling SUVmin-max: 0-10 was performed by three teams with different levels of experience. Team 1 repeated contouring at a different time point, resulting in n = 4 manual contours. (2) Semi-automatic contouring approaches using SUVmax thresholds of 20-50% were performed. Interobserver agreement was assessed for manual contouring by calculating the Dice Similarity Coefficient (DSC) and for all approaches sensitivity, specificity were calculated by dividing the prostate in each CT slice into four equal quadrants under consideration of histopathology as standard of reference. Results: Manual contouring yielded an excellent interobserver agreement with a median DSC of 0.90 (range 0.87-0.94). Volumes derived from scaling SUVmin-max 0-10 showed no statistically significant difference from GTV-Histo and high sensitivities (median 87%, range 84-90%) and specificities (median 96%, range 96-100%). GTVs using semi-automatic segmentation applying a threshold of 20-40% of SUVmax showed no significant difference in absolute volumes to GTV-Histo, GTV-SUV50% was significantly smaller. Best performing semi-automatic contour (GTV-SUV20%) achieved high sensitivity (median 93%) and specificity (median 96%). There was no statistically significant difference to SUVmin-max 0-10. Conclusion: Manual contouring with PET scaling SUVmin-max 0-10 and semi-automatic contouring applying a threshold of 20% of SUVmax achieved high sensitivities and very high specificities and are recommended for [18F]PSMA-1007 PET based focal therapy approaches. Providing high specificities, semi-automatic approaches applying thresholds of 30-40% of SUVmax are recommend for biopsy guidance

Abstract: Background Nivolumab monotherapy is approved for the treatment of advanced renal cell carcinoma (aRCC) after prior therapy on the basis of results from CheckMate 025. Objective The NORA (NivOlumab in Renal cell cArcinoma) noninterventional study (NIS) aims to capture real-world data to complement the pivotal CheckMate 025 clinical trial. Design, setting, and participants NORA is a prospective, multicenter NIS in Germany. Consenting patients with aRCC of any subtype who started nivolumab after previous therapy were eligible. Outcome measurements and statistical analysis The primary objective was to estimate overall survival (OS) in the overall population and relevant subgroups. Secondary objectives included progression-free survival (PFS), the objective response rate (ORR), the duration of response (DOR), safety, and patient-reported outcomes (PROs). Baseline characteristics were summarized using descriptive statistics. OS and PFS were estimated via the Kaplan-Meier-method. Results and limitations A total of 228 patients with aRCC were eligible. The median age was 70 yr, 71% were male, 14% had favorable, 58% had intermediate, and 15% had poor International Metastatic RCC Database Consortium risk (12% missing information). The median follow-up was 37 mo. In the overall population, median OS was 24 mo (95% confidence interval [CI] 19-28) and median PFS was 5.3 mo (95% CI 3.9-6.7). The ORR was 20% and the median DOR was 28 mo (95% CI 16-not estimable). No new safety signals emerged (46% and 15% of patients had treatment-related adverse events of all grades and grade 3-4, respectively; there was 1 treatment-related death due to liver failure). PROs did not reveal detriments during the study duration. Limitations include the lack of central pathology review and no standardization for imaging evaluation and toxicity assessment. Conclusions Effectiveness and safety in this real-world population were in line with the pivotal clinical trial and support the use of nivolumab after prior systemic therapy in a broad aRCC population

Abstract: Introduction: An accurate delineation of the intraprostatic gross tumor volume (GTV) is of importance for focal treatment in patients with primary prostate cancer (PCa). Multiparametric MRI (mpMRI) is the standard of care for lesion detection but has been shown to underestimate GTV. This study investigated how far the GTV has to be expanded in MRI in order to reach concordance with the histopathological reference and whether this strategy is practicable in clinical routine. Patients and Methods: Twenty-two patients with planned prostatectomy and preceded 3 Tesla mpMRI were prospectively examined. After surgery, PCa contours delineated on histopathological slides (GTV-Histo) were superimposed on MRI using ex-vivo imaging as support for co-registration. According to the PI-RADSv2 classification, GTV was manually delineated in MRI (GTV-MRI) by two experts in consensus. For volumetric analysis, we compared GTV-MRI and GTV-Histo. Subsequently, we isotropically enlarged GTV-MRI in 1 mm increments within the prostate and also compared those with GTV-Histo regarding the absolute volumes. For evaluating the spatial accuracy, we considered the coverage ratio of GTV-Histo, the Sørensen-Dice coefficient (DSC), as well as the contact with the urethra. Results: In 19 of 22 patients MRI underestimated the intraprostatic tumor volume compared to histopathological reference: median GTV-Histo (4.7 cm3, IQR: 2.5-18.8) was significantly (p0.001) lager than median GTV-MRI (2.6 cm3, IQR: 1.2-6.9). A median expansion of 1 mm (range: 0-4 mm) adjusted the initial GTV-MRI to at least the volume of GTV-Histo (GTVexp-MRI). Original GTV-MRI and expansion with 1, 2, 3, and 4 mm covered in median 39% (IQR: 2%-78%), 62% (10%-91%), 70% (15%-95%), 80% (21-100), 87% (25%-100%) of GTV-Histo, respectively. Best DSC (median: 0.54) between GTV-Histo and GTV-MRI was achieved by median expansion of 2 mm. The urethra was covered by initial GTVs-MRI in eight patients (36%). After applying an expansion with 2 mm the urethra was covered in one more patient by GTV-MRI.br