[en] Highlights: • The prostate-specific antigen density (PSAD) was calculated for the TZ (TZPSAD). • TZPSAD may be a better surrogate marker for cancer aggressiveness than PSAD. • A TZPSAD threshold of 0.22 ng/ml² may help in risk stratification. - Abstract: Purpose: To compare the correlation of transition zone prostate-specific antigen density (TZPSAD) versus whole gland (WG) density (PSAD) with Gleason score.

[en] To assess interreader agreement of manual prostate cancer lesion segmentation on multiparametric MR images (mpMRI). The secondary aim was to compare tumor volume estimates between MRI segmentation and transperineal template saturation core needle biopsy (TTSB). We retrospectively reviewed patients who had undergone mpMRI of the prostate at our institution and who had received TTSB within 190 days of the examination. Seventy-eight cancer lesions with Gleason score of at least 3 + 4 = 7 were manually segmented in T2-weighted images by 3 radiologists and 1 medical student. Twenty lesions were also segmented in apparent diffusion coefficient (ADC) and dynamic contrast enhanced (DCE) series. First, 20 volumetric similarity scores were computed to quantify interreader agreement. Second, manually segmented cancer lesion volumes were compared with TTSB-derived estimates by Bland-Altman analysis and Wilcoxon testing. Interreader agreement across all readers was only moderate with mean T2 Dice score of 0.57 (95%CI 0.39–0.70), volumetric similarity coefficient of 0.74 (0.48–0.89), and Hausdorff distance of 5.23 mm (3.17–9.32 mm). Discrepancy of volume estimate between MRI and TTSB was increasing with tumor size. Discrepancy was significantly different between tumors with a Gleason score 3 + 4 vs. higher grade tumors (0.66 ml vs. 0.78 ml; p = 0.007). There were no significant differences between T2, ADC, and DCE segmentations. We found at best moderate interreader agreement of manual prostate cancer segmentation in mpMRI. Additionally, our study suggests a systematic discrepancy between the tumor volume estimate by MRI segmentation and TTSB core length, especially for large and high-grade tumors.

[en] Given the good correlation between PSMA expression and intraglandular tumour aggressiveness based on immunohistochemistry, there is increasing interest in ⁶⁸Ga-PSMA-11 PET/MRI for staging prostate cancer (PCA). Therefore, accurate knowledge of prostate anatomy as well as normal distribution of PSMA within the prostate gland is becoming essential. The aim of this study was to investigate the physiological intraprostatic distribution of ⁶⁸Ga-PSMA-11. We retrospectively analysed all patients who underwent a staging ⁶⁸Ga-PSMA-11 PET/MRI scan between June 2016 and January 2018 for high-risk PCA, underwent radical prostatectomy in our institution, and gave written consent for further data analysis. In each patient, standardized volumes of interest (VOIs) were placed bilaterally in the central, transition and peripheral zones within the zonal anatomy according to T2 weighted sequences in the axial and coronal planes. VOIs were only placed if they were safely within healthy tissue without spillover from the PCA. SUV_max and SUV_mean were determined and their differences among the regions were assessed using the Wilcoxon signed-ranks test. Of 283 consecutive patients scanned with ⁶⁸Ga-PSMA-11 PET/MR, 31 were analysed. A total of 133 VOIs were placed, 46 in the central zone, 41 in the transition zone and 46 in the peripheral zone. Differences in SUV_max between the central zone (mean 3.9 ± 0.58) and transition zone (mean 3.2 ± 0.59) and between the central zone and peripheral zone (mean 2.7 ± 0.54) were statistically significant (both p < 0.001). Our results suggest that higher ⁶⁸Ga-PSMA-11 accumulation in the central zone than in the transition and peripheral zones is normal, and leads to a pattern resembling ''Mickey Mouse ears'' on ⁶⁸Ga-PSMA-11 PET. This pattern could be helpful in avoiding false-positive interpretations of PET scans. (orig.)

[en] In oral squamous cell carcinoma (OSCC), depth of invasion (DOI) is an important predictive, prognostic, and staging parameter. While it is known that DOI can be estimated from preoperative imaging, an analysis of measurements variations according to imaging modality and to depth of tumor itself is lacking. The aim of the study was to assess the accuracy of imaging-based estimation of DOI in relation with the tumor histological DOI.

[en] Radical prostatectomy with extended pelvic lymph node dissection (ePLND) is a curative treatment option for patients with clinically significant localised prostate cancer. The decision to perform an ePLND can be challenging because the overall incidence of lymph node metastasis is relatively low and ePLND is not free of complications. Using current clinical nomograms to identify patients with nodal involvement, approximately 75-85% of ePLNDs performed are negative. The aim of this study was to assess the added value of ${}^{68}$Ga-PSMA-11 PET in predicting lymph node metastasis in men with intermediate- or high-risk prostate cancer. ${}^{68}$Ga-PSMA-11 PET scans of 60 patients undergoing radical prostatectomy with ePLND were reviewed for qualitative (visual) assessment of suspicious nodes and assessment of quantitative parameters of the primary tumour in the prostate (SUV${}_{max}$, total activity (PSMA${}_{total}$) and PSMA positive volume (PSMA${}_{vol}$)). Ability of quantitative PET parameters to predict nodal metastasis was assessed with receiver operating characteristics (ROC) analysis. A multivariable logistic regression model combining PSA, Gleason score, visual nodal status on PET and primary tumour PSMA${}_{total}$ was built. Net benefit at each risk threshold was compared with five nomograms: MSKCC nomogram, Yale formula, Roach formula, Winter nomogram and Partin tables (2016). Overall, pathology of ePLND specimens revealed 31 pelvic metastatic lymph nodes in 12 patients. ${}^{68}$Ga-PSMA-11 PET visual analysis correctly detected suspicious nodes in 7 patients, yielding a sensitivity of 58% and a specificity of 98%. The area under the ROC curve for primary tumour SUV${}_{max}$ was 0.70, for PSMA${}_{total}$ 0.76 and for PSMA${}_{vol}$ 0.75. The optimal cut-off for nodal involvement was PSMA${}_{total}$ > 49.1. The PET model including PSA, Gleason score and quantitative PET parameters had a persistently higher net benefit compared with all clinical nomograms. Our model combining PSA, Gleason score and visual lymph node analysis on ${}^{68}$Ga-PSMA-11 PET with PSMA${}_{total}$ of the primary tumour showed a tendency to improve patient selection for ePLND over the currently used clinical nomograms. Although this result has to be validated, ${}^{68}$Ga-PSMA-11 PET showed the potential to reduce unnecessary surgical procedures in patients with intermediate- or high-risk prostate cancer.

[en] 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 ${}^{68}$Ga-PSMA-11-PET examinations. RPE specimens of 62 patients with preoperative ${}^{68}$Ga-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${}_{\mathrm{\%<!--\; \%\; -->}neg}$) were correlated with spatially corresponding SUV${}_{max}$ on ${}^{68}$Ga-PSMA-11-PET in a multidisciplinary analysis. 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${}_{\mathrm{\%<!--\; \%\; -->}neg}$. PSMA${}_{\mathrm{\%<!--\; \%\; -->}neg}$, 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${}_{\mathrm{\%<!--\; \%\; -->}neg}$ 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${}_{\mathrm{\%<!--\; \%\; -->}neg}$ (p < 0.01, OR = 9.629) and growth pattern (p = 0.0497, OR = 306.537) as significant predictors for a negative PSMA-PET scan. We describe PSMA${}_{\mathrm{\%<!--\; \%\; -->}neg}$, infiltrative growth pattern, smaller tumour size and WHO/ISUP grade group 2 as parameters associated with a lower ${}^{68}$Ga-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.

[en] To develop and evaluate a lymph node invasion (LNI) prediction model for men staged with [${}^{68}$Ga]Ga-PSMA-11 PET. A consecutive sample of intermediate to high-risk prostate cancer (PCa) patients undergoing [${}^{68}$Ga]Ga-PSMA-11 PET, extended pelvic lymph node dissection (ePLND), and radical prostatectomy (RP) at two tertiary referral centers were retrospectively identified. The training cohort comprised 173 patients (treated between 2013 and 2017), the validation cohort 90 patients (treated between 2016 and 2019). Three models for LNI prediction were developed and evaluated using cross-validation. Optimal risk-threshold was determined during model development. The best performing model was evaluated and compared to available conventional and multiparametric magnetic resonance imaging (mpMRI)-based prediction models using area under the receiver operating characteristic curves (AUC), calibration plots, and decision curve analysis (DCA). A combined model including prostate-specific antigen, biopsy Gleason grade group, [${}^{68}$Ga]Ga Ga-PSMA-11 positive volume of the primary tumor, and the assessment of the [${}^{68}$Ga]Ga-PSMA-11 report N-status yielded an AUC of 0.923 (95% CI 0.863-0.984) in the external validation. Using a cutoff of ≥ 17%, 44 (50%) ePLNDs would be spared and LNI missed in one patient (4.8%). Compared to conventional and MRI-based models, the proposed model showed similar calibration, higher AUC (0.923 (95% CI 0.863-0.984) vs. 0.700 (95% CI 0.548-0.852)---0.824 (95% CI 0.710-0.938)) and higher net benefit at DCA. Our results indicate that information from [${}^{68}$Ga]Ga-PSMA-11 may improve LNI prediction in intermediate to high-risk PCa patients undergoing primary staging especially when combined with clinical parameters. For better LNI prediction, future research should investigate the combination of information from both PSMA PET and mpMRI for LNI prediction in PCa patients before RP.

[en] Recently, a significant association was shown between novel growth patterns on histopathology of prostate cancer (PCa) and prostate-specific membrane antigen (PSMA) uptake on [${}^{68}$Ga]PSMA-PET. It is the aim of this study to evaluate the association between these growth patterns and ADC (mm${}^2$/1000 s) values in comparison to [${}^{68}$Ga]PSMA uptake on PET/MRI. We retrospectively evaluated patients who underwent [${}^{68}$Ga]PSMA PET/MRI for staging or biopsy guidance, followed by radical prostatectomy at our institution between 07/2016 and 01/2020. The dominant lesion per patient was selected based on histopathology and correlated to PET/MRI in a multidisciplinary meeting, and quantified using SUV${}_{max}$ for PSMA uptake and ADC${}_{mean}$ for diffusion restriction. PCa growth pattern was classified as expansive (EXP) or infiltrative (INF) according to its properties of forming a tumoral mass or infiltrating diffusely between benign glands by two independent pathologists. Furthermore, the corresponding WHO2016 ISUP tumor grade was evaluated. The t test was used to compare means, Pearson's test for categorical correlation, Cohen's kappa test for interrater agreement, and ROC curve to determine the best cutoff. Sixty-two patients were included (mean PSA 11.7 ± 12.5). The interrater agreement between both pathologists was almost perfect with κ = 0.81. While 25 lesions had an EXP-growth with an ADC${}_{mean}$ of 0.777 ± 0.109, 37 showed an INF-growth with a significantly higher ADC${}_{mean}$ of 1.079 ± 0.262 (p < 0.001). We also observed a significant difference regarding PSMA SUV${}_{max}$ for the EXP-growth (19.2 ± 10.9) versus the INF-growth (9.4 ± 6.2, p < 0.001). Within the lesions encompassing the EXP- or the INF-growth, no significant correlation between the ISUP groups and ADC${}_{mean}$ could be observed (p = 0.982 and p = 0.861, respectively). PCa with INF-growth showed significantly lower SUV${}_{max}$ and higher ADC${}_{mean}$ values compared to PCa with EXP-growth. Within the growth groups, ADC${}_{mean}$ values were independent from ISUP grading.

[en] Ultrasound-guided biopsy (US biopsy) with 10-12 cores has a suboptimal sensitivity for clinically significant prostate cancer (sigPCa). If US biopsy is negative, magnetic resonance imaging (MRI)-guided biopsy is recommended, despite a low specificity for lesions with score 3-5 on Prostate Imaging Reporting and Data System (PIRADS). Screening and biopsy guidance using an imaging modality with high accuracy could reduce the number of unnecessary biopsies, reducing side effects. The aim of this study was to assess the performance of positron emission tomography/MRI with ${}^{68}$Ga-labeled prostate-specific membrane antigen (PSMA-PET/MRI) to detect and localize primary sigPCa (ISUP grade group 3 and/or cancer core length ≥ 6 mm) and guide biopsy. Prospective, open-label, single-center, non-randomized, diagnostic accuracy study including patients with suspected PCa by elevation of prostate-specific antigen (PSA) level and a suspicious lesion (PIRADS ≥ 3) on multiparametric MRI (mpMRI). Forty-two patients underwent PSMA-PET/MRI followed by both PSMA-PET/MRI-guided and section-based saturation template biopsy between May 2017 and February 2019. Primary outcome was the accuracy of PSMA-PET/MRI for biopsy guidance using section-based saturation template biopsy as the reference standard. SigPCa was found in 62% of the patients. Patient-based sensitivity, specificity, negative and positive predictive value, and accuracy for sigPCa were 96%, 81%, 93%, 89%, and 90%, respectively. One patient had PSMA-negative sigPCa. Eight of nine false-positive lesions corresponded to cancer on prostatectomy and one in six false-negative lesions was negative on prostatectomy. PSMA-PET/MRI has a high accuracy for detecting sigPCa and is a promising tool to select patients with suspicion of PCa for biopsy.