PD-L1 as a Urine Biomarker in Renal Cell Carcinoma-A Case Series and Proof-of-Concept Study.

BACKGROUND: Renal cell carcinoma (RCC) is among the most lethal urologic malignancies once metastatic. Current treatment approaches for metastatic RCC (mRCC) involve immune checkpoint inhibitors (ICIs) that target the PD-L1/PD-1 axis. High PD-L1 expression in tumor tissue has been identified as a negative prognostic factor in RCC. However, the role of PD-L1 as a liquid biomarker has not yet been fully explored. Herein, we analyze urine levels of PD-L1 in mRCC patients before and after either ICI therapy or surgical intervention, as well as in a series of patients with treatment-naïve RCC. PATIENTS AND METHODS: The mid-stream urine of patients with mRCC (n = 4) or treatment-naïve RCC, i.e., prior to surgery from two centers (cohort I, n = 49: cohort II, n = 29) was analyzed for PD-L1 by ELISA. The results from cohort I were compared to a control group consisting of patients treated for non-malignant urologic diseases (n = 31). In the mRCC group, urine PD-L1 levels were measured before and after tumor nephrectomy (n = 1) or before and after ICI therapy (n = 3). Exosomal PD-L1 in the urine was analyzed in selected patients by immunoblotting. RESULTS: A strong decrease in urine PD-L1 levels was found after tumor nephrectomy or following systemic treatment with ICIs. In patients with treatment-naïve RCC (cohort I), urine PD-L1 levels were significantly elevated in the RCC group in comparison to the control group (median 59 pg/mL vs. 25.7 pg/mL, p = 0.011). PD-L1 urine levels were found to be elevated, in particular, in low-grade RCCs in cohorts I and II. Exosomal PD-L1 was detected in the urine of a subset of patients. CONCLUSION: In this proof-of-concept study, we show that PD-L1 can be detected in the urine of RCC patients. Urine PD-L1 levels were found to correlate with the treatment response in mRCC patients and were significantly elevated in treatment-naïve RCC patients.

Weakly Supervised MRI Slice-Level Deep Learning Classification of Prostate Cancer Approximates Full Voxel- and Slice-Level Annotation: Effect of Increasing Training Set Size.

BACKGROUND: Weakly supervised learning promises reduced annotation effort while maintaining performance. PURPOSE: To compare weakly supervised training with full slice-wise annotated training of a deep convolutional classification network (CNN) for prostate cancer (PC). STUDY TYPE: Retrospective. SUBJECTS: One thousand four hundred eighty-nine consecutive institutional prostate MRI examinations from men with suspicion for PC (65 ± 8 years) between January 2015 and November 2020 were split into training (N = 794, enriched with 204 PROSTATEx examinations) and test set (N = 695). FIELD STRENGTH/SEQUENCE: 1.5 and 3T, T2-weighted turbo-spin-echo and diffusion-weighted echo-planar imaging. ASSESSMENT: Histopathological ground truth was provided by targeted and extended systematic biopsy. Reference training was performed using slice-level annotation (SLA) and compared to iterative training utilizing patient-level annotations (PLAs) with supervised feedback of CNN estimates into the next training iteration at three incremental training set sizes (N = 200, 500, 998). Model performance was assessed by comparing specificity at fixed sensitivity of 0.97 [254/262] emulating PI-RADS ≥ 3, and 0.88-0.90 [231-236/262] emulating PI-RADS ≥ 4 decisions. STATISTICAL TESTS: Receiver operating characteristic (ROC) and area under the curve (AUC) was compared using DeLong and Obuchowski test. Sensitivity and specificity were compared using McNemar test. Statistical significance threshold was P = 0.05. RESULTS: Test set (N = 695) ROC-AUC performance of SLA (trained with 200/500/998 exams) was 0.75/0.80/0.83, respectively. PLA achieved lower ROC-AUC of 0.64/0.72/0.78. Both increased performance significantly with increasing training set size. ROC-AUC for SLA at 500 exams was comparable to PLA at 998 exams (P = 0.28). ROC-AUC was significantly different between SLA and PLA at same training set sizes, however the ROC-AUC difference decreased significantly from 200 to 998 training exams. Emulating PI-RADS ≥ 3 decisions, difference between PLA specificity of 0.12 [51/433] and SLA specificity of 0.13 [55/433] became undetectable (P = 1.0) at 998 exams. Emulating PI-RADS ≥ 4 decisions, at 998 exams, SLA specificity of 0.51 [221/433] remained higher than PLA specificity at 0.39 [170/433]. However, PLA specificity at 998 exams became comparable to SLA specificity of 0.37 [159/433] at 200 exams (P = 0.70). DATA CONCLUSION: Weakly supervised training of a classification CNN using patient-level-only annotation had lower performance compared to training with slice-wise annotations, but improved significantly faster with additional training data. EVIDENCE LEVEL: 3 TECHNICAL EFFICACY: Stage 2.

Long-Term Survival of Patients with Stage T1N0M1 Renal Cell Carcinoma.

Metastatic renal cell carcinoma (RCC) is among the most lethal urological malignancies. However, small, localized RCCs (≤7 cm, stage T1) have an excellent prognosis. There is a rare patient subgroup diagnosed with synchronous distant metastasis (T1N0M1), of which very little is known in terms of survival outcomes and underlying disease biology. Herein, we examined the long-term survival of 27 patients with clear cell RCC (ccRCC) stage T1N0M1 in comparison to 18 patients without metastases (T1N0M0). Tumor tissue was stained by immunohistochemistry for CD8+ tumor infiltrating lymphocytes (TILs). As expected, patients with stage T1N0M1 showed a significantly worse median cancer specific survival (CSS; 2.8 years) than patients with stage T1N0M0 (17.7 years; HR 0.077; 95% CI, 0.022-0.262). However, eight patients (29.6%) with ccRCC stage T1N0M1 survived over five years, and three of those patients (11.1%) survived over a decade. Some of these patients benefitted from an intensified, multimodal treatment including metastasis-directed therapy. The number of CD8+ TILs was substantially higher in stage T1N0M1 ccRCCs than in stage T1N0M0 ccRCCs, suggesting a more aggressive tumor biology. In conclusion, long-term survival is possible in patients with ccRCC stage T1N0M1, with some patients benefitting from an intensified, multimodal treatment approach.

Addressing image misalignments in multi-parametric prostate MRI for enhanced computer-aided diagnosis of prostate cancer.

Prostate cancer (PCa) diagnosis on multi-parametric magnetic resonance images (MRI) requires radiologists with a high level of expertise. Misalignments between the MRI sequences can be caused by patient movement, elastic soft-tissue deformations, and imaging artifacts. They further increase the complexity of the task prompting radiologists to interpret the images. Recently, computer-aided diagnosis (CAD) tools have demonstrated potential for PCa diagnosis typically relying on complex co-registration of the input modalities. However, there is no consensus among research groups on whether CAD systems profit from using registration. Furthermore, alternative strategies to handle multi-modal misalignments have not been explored so far. Our study introduces and compares different strategies to cope with image misalignments and evaluates them regarding to their direct effect on diagnostic accuracy of PCa. In addition to established registration algorithms, we propose 'misalignment augmentation' as a concept to increase CAD robustness. As the results demonstrate, misalignment augmentations can not only compensate for a complete lack of registration, but if used in conjunction with registration, also improve the overall performance on an independent test set.

CD15 is a risk predictor and a novel target in clear cell renal cell carcinoma.

INTRODUCTION: Tumor cells use adhesion molecules like CD15 or sialylCD15 (sCD15) for metastatic spreading. We analyzed the expression of CD15 and sCD15 in clear cell renal cell carcinoma (ccRCC) regarding prognosis. METHODS: A tissue microarray containing tissue specimens of 763 patients with ccRCC was immunohistochemically stained for CD15 and sCD15, their expression quantified using digital image analysis and the impact on patients' survival analyzed. The cell lines 769p and 786o were stimulated with CD15 or control antibody in vitro and the effects on pathways activating AP-1 and tumor cell migration examined. RESULTS: ccRCC showed a broad range of CD15 and sCD15 expression. A high CD15 expression was significantly associated with favorable outcome (p<0.01) and low-grade tumor differentiation (p<0.001), whereas sCD15 had no significant prognostic value. Tumors with synchronous distant metastasis had a significantly lower CD15 expression compared to tumors without any (p<0.001) or with metachronous metastasis (p<0.01). Tumor cell migration was significantly reduced after CD15 stimulation in vitro, but there were no major effects on activating pathways of AP-1. CONCLUSION: CD15, but not sCD15, qualifies as a biomarker for risk stratification and as an interesting novel target in ccRCC. Moreover, the data indicates a contribution of CD15 to metachronous metastasis. Further research is warranted to decipher the intracellular pathways of CD15 signaling in ccRCC in order to characterize the CD15 effects on ccRCC more precisely.

Digital Spatial Profiling Identifies the Tumor Periphery as a Highly Active Biological Niche in Clear Cell Renal Cell Carcinoma.

Clear cell renal cell carcinoma (ccRCC) is characterized by a high degree of intratumoral heterogeneity (ITH). Besides genomic ITH, there is considerable functional ITH, which encompasses spatial niches with distinct proliferative and signaling activities. The full extent of functional spatial heterogeneity in ccRCC is incompletely understood. In the present study, a total of 17 ccRCC tissue specimens from different sites (primary tumor, n = 11; local recurrence, n = 1; distant metastasis, n = 5) were analyzed using digital spatial profiling (DSP) of protein expression. A total of 128 regions of interest from the tumor periphery and tumor center were analyzed for the expression of 46 proteins, comprising three major signaling pathways as well as immune cell markers. Results were correlated to clinico-pathological variables. The differential expression of granzyme B was validated using conventional immunohistochemistry and was correlated to the cancer-specific patient survival. We found that a total of 37 proteins were differentially expressed between the tumor periphery and tumor center. Thirty-five of the proteins were upregulated in the tumor periphery compared to the center. These included proteins involved in cell proliferation, MAPK and PI3K/AKT signaling, apoptosis regulation, epithelial-to-mesenchymal transition, as well as immune cell markers. Among the most significantly upregulated proteins in the tumor periphery was granzyme B. Granzyme B upregulation in the tumor periphery correlated with a significantly reduced cancer-specific patient survival. In conclusion, this study highlights the unique cellular contexture of the tumor periphery in ccRCC. The correlation between granzyme B upregulation in the tumor periphery and patient survival suggests local selection pressure for aggressive tumor growth and disease progression. Our results underscore the potential of spatial biology for biomarker discovery in ccRCC and cancer in general.

Are T2WI PI-RADS sub-scores of transition zone prostate lesions biased by DWI information? A multi-reader, single-center study.

PURPOSE: According to PI-RADS v2.1, T2-weighted imaging (T2WI) is the dominant sequence for transition zone (TZ) lesions. This study aimed to assess, whether diffusion-weighted imaging (DWI) information influences the assignment of T2WI scores. METHOD: Out of 283 prostate MRI examinations with correlated biopsy results, fourty-four patients were selected retrospectively: first, 22 patients with a TZ lesion with T2WI and DWI scores ≥ 4, to represent lesions with unequivocal suspicion on T2WI and DWI. Second, 22 additional patients with TZ lesions of similar T2WI appearance but with corresponding DWI score ≤ 3 were added as control. Four residents and one board-certified radiologist each performed two assessments of the included patients: First, only T2WI was available (T2-only read); second, both T2WI and DWI sequences were available (biparametric read). Lesion scores were assessed using Wilcoxon signed-rank test, inter-reader agreement using weighted kappa and Kendall's W statistics, and sensitivity/specificity using McNemar test. RESULTS: The T2WI scores were significantly different between the T2-only and biparametric read for 3 out of 4 residents (p ≤ 0.049) but not for the radiologist. The overall PI-RADS scores derived from the two reading sessions differed considerably for 35/220 cases (all readers pooled). Inter-reader agreement was fair for the T2WI and overall PI-RADS scores (mean kappa 0.27-0.30) and moderate for the DWI scores (mean kappa 0.43). CONCLUSIONS: For inexperienced readers, assessment of T2WI is variable and potentially biased by availability of DWI information, which can lead to changes of overall PI-RADS score and consequently clinical management. Assessment of T2WI should be performed before reviewing DWI to ensure non-biased interpretation of TZ lesions in the dominant sequence.

Same-day repeatability and Between-Sequence reproducibility of Mean ADC in PI-RADS lesions.

PURPOSE: This study aimed to assess repeatability after repositioning (inter-scan), intra-rater, inter-rater and inter-sequence variability of mean apparent diffusion coefficient (ADC) measurements in MRI-detected prostate lesions. METHOD: Forty-three patients with suspicion for prostate cancer were included and received a clinical prostate bi-/multiparametric MRI examination with repeat scans of the T2-weighted and two DWI-weighted sequences (ssEPI and rsEPI). Two raters (R1 and R2) performed single-slice, 2D regions of interest (2D-ROIs) and 3D-segmentation-ROIs (3D-ROIs). Mean bias, corresponding limits of agreement (LoA), mean absolute difference, within-subject coefficient of variation (CoV) and repeatability/reproducibility coefficient (RC/RDC) were calculated. Bradley & Blackwood test was used for variance comparison. Linear mixed models (LMM) were used to account for multiple lesions per patient. RESULTS: Inter-scan repeatability, intra-rater and inter-sequence reproducibility analysis of ADC showed no significant bias. 3D-ROIs demonstrated significantly less variability than 2D-ROIs (p < 0.01). Inter-rater comparison demonstrated small significant systematic bias of 57 × 10-6 mm2/s for 3D-ROIs (p < 0.001). Intra-rater RC, with the lowest variation, was 145 and 189 × 10-6 mm2/s for 3D- and 2D-ROIs, respectively. For 3D-ROIs of ssEPI, RCs and RDCs were 190-198 × 10-6 mm2/s for inter-scan, inter-rater and inter-sequence variation. No significant differences were found for inter-scan, inter-rater and inter-sequence variability. CONCLUSIONS: In a single-scanner setting, single-slice ADC measurements showed considerable variation, which may be lowered using 3D-ROIs. For 3D-ROIs, we propose a cut-off of âˆ¼ 200 × 10-6 mm2/s for differences introduced by repositioning, rater or sequence effects. The results suggest that follow-up measurements should be possible by different raters or sequences.

Evaluation of Gas 6 as a Prognostic Marker in Papillary Renal Cell Carcinoma.

INTRODUCTION: Growth arrest-specific protein 6 (Gas 6) is a ligand that plays a role in proliferation and migration of cells. For several tumor entities, high levels of Gas 6 are associated with poorer survival. We examined the prognostic role of Gas 6 in renal cell carcinoma (RCC), especially in papillary RCC (pRCC), which is still unclear. METHODS: The patients' sample collection is a joint collaboration of the PANZAR consortium. Patients' medical history and tumor specimens were collected from n = 240 and n = 128 patients with type 1 and 2 pRCC, respectively. Expression of Gas 6 was determined by immunohistochemistry. RESULTS: In total, Gas 6 staining was evaluable in 180 of 240 type 1 and 110 of 128 type 2 pRCC cases. Kaplan-Meier analysis disclosed no significant difference in 5-year overall survival for all pRCC nor either subtype. Also, Gas+ and Gas- groups did not significantly differ in any tumor or patient characteristics. CONCLUSION: Gas 6 was not found to be an independent prognostic marker in pRCC. Future studies are warranted to determine if Gas 6 plays a role as prognostic marker or therapeutic target in pRCC.

An artificial intelligence-based chatbot for prostate cancer education: Design and patient evaluation study.

Introduction: Artificial intelligence (AI) is increasingly used in healthcare. AI-based chatbots can act as automated conversational agents, capable of promoting health and providing education at any time. The objective of this study was to develop and evaluate a user-friendly medical chatbot (prostate cancer communication assistant (PROSCA)) for provisioning patient information about early detection of prostate cancer (PC). Methods: The chatbot was developed to provide information on prostate diseases, diagnostic tests for PC detection, stages, and treatment options. Ten men aged 49 to 81 years with suspicion of PC were enrolled in this study. Nine of ten patients used the chatbot during the evaluation period and filled out the questionnaires on usage and usability, perceived benefits, and potential for improvement. Results: The chatbot was straightforward to use, with 78% of users not needing any assistance during usage. In total, 89% of the chatbot users in the study experienced a clear to moderate increase in knowledge about PC through the chatbot. All study participants who tested the chatbot would like to re-use a medical chatbot in the future and support the use of chatbots in the clinical routine. Conclusions: Through the introduction of the chatbot PROSCA, we created and evaluated an innovative evidence-based health information tool in the field of PC, allowing targeted support for doctor-patient communication and offering great potential in raising awareness, patient education, and support. Our study revealed that a medical chatbot in the field of early PC detection is readily accepted and benefits patients as an additional informative tool.

Detection Rate of Prostate Cancer in Repeat Biopsy after an Initial Negative Magnetic Resonance Imaging/Ultrasound-Guided Biopsy.

A negative multiparametric magnetic resonance imaging (mpMRI)-guided prostate biopsy in patients with suspected prostate cancer (PC) results in clinical uncertainty, as the biopsy can be false negative. The clinical challenge is to determine the optimal follow-up and to select patients who will benefit from repeat biopsy. In this study, we evaluated the rate of significant PC (sPC, Gleason score ≥7) and PC detection in patients who received a follow-up mpMRI/ultrasound-guided biopsy for persistent PC suspicion after a negative mpMRI/ultrasound-guided biopsy. We identified 58 patients at our institution that underwent repeat targeted biopsy in case of PI-RADS lesions and systematic saturation biopsy between 2014 and 2022. At the initial biopsy, the median age was 59 years, and the median prostate specific antigen level was 6.7 ng/mL. Repeat biopsy after a median of 18 months detected sPC in 3/58 (5%) patients and Gleason score 6 PC in 11/58 (19%). Among 19 patients with a downgraded PI-RADS score at the follow-up mpMRI, none had sPC. In conclusion, men with an initial negative mpMRI/ultrasound-guided biopsy had a high likelihood of not harboring sPC at repeat biopsy (95%). Due to the small size of the study, further research is recommended.

Genomic instability in individuals with sex determination defects and germ cell cancer.

The ability to transmit genetic information through generations depends on the preservation of genome integrity. Genetic abnormalities affect cell differentiation, causing tissue specification defects and cancer. We addressed genomic instability in individuals with Differences of Sex Development (DSD), characterized by gonadal dysgenesis, infertility, high susceptibility for different types of cancer, especially Germ Cell Tumors (GCT), and in men with testicular GCTs. Whole proteome analysis of leukocytes, supported by specific gene expression assessment, and dysgenic gonads characterization, uncovered DNA damage phenotypes with altered innate immune response and autophagy. Further examination of DNA damage response revealed a reliance on deltaTP53, which was compromised by mutations in the transactivation domain in DSD-individuals with GCT. Accordingly, drug-induced rescue of DNA damage was achieved by autophagy inhibition but not by stabilization of TP53 in DSD-individuals' blood in vitro. This study elucidates possibilities for prophylactic treatments of DSD-individuals, as well as new diagnostic approaches of GCT.

Senescent Tumor Cells Are Frequently Present at the Invasion Front: Implications for Improving Disease Control in Patients with Locally Advanced Prostate Cancer.

INTRODUCTION: Local tumor invasion is a critical factor for the outcome of men with prostate cancer. In particular, seminal vesicle invasion (SVI) has been reported to be associated with a more unfavorable prognosis. A better understanding of the functional state of invading prostate cancer cells is crucial to develop novel therapeutic strategies for patients with locally advanced disease. METHODS: The prognostic impact of local tumor progression was ascertained in over 1,000 men with prostate cancer. Prostate cancer specimens were stained by double-immunohistochemistry for the proliferation marker Ki-67 and the senescence marker p16INK4A. The migratory properties of senescent prostate cancer cells were analyzed in vitro using a wound healing assay and immunofluorescence microscopy for p16INK4A. RESULTS: We confirm the notion that patients with SVI have a more unfavorable prognosis than patients with extraprostatic extension alone. Surprisingly, we found that the tumor invasion front frequently harbors p16INK4A-positive and Ki-67-negative, i.e., senescent, tumor cells. While the intraprostatic tumor periphery was a hotspot for both proliferation and expression of p16INK4A, the area of SVI showed less proliferative activity but was at the same time a hotspot of cells with increased nuclear p16INK4A expression. Senescence was associated with an accelerated migration of prostate cancer cells in vitro. CONCLUSION: This proof-of-concept study shows that invading prostate cancer cells frequently show signs of cellular senescence. This finding may open new avenues for neoadjuvant and adjuvant treatment concepts in men with locally advanced prostate cancer.

The Mobile Patient Information Assistant (PIA) App during the Inpatient Surgical Hospital Stay: Evaluation of Usability and Patient Approval.

Mobile eHealth apps are becoming increasingly important tools in healthcare management, capable of providing education and support at any time. There is little knowledge about surgical patients' appreciation and use of these apps. The objective of this study was to develop and evaluate a user-friendly medical app (PIA; Patient Information Assistant) for providing individual patient information before and after inpatient urological surgery. Twenty-two patients aged 35 to 75 years were provided with timely information, push notifications, and personalized agendas (e.g., date of presentation, time of surgery, time of doctor's consultation, imaging appointment) via the PIA app. Of the 22 patients, 19 evaluated the PIA app in terms of usage and usability, benefits, and potential for improvement. Of the study participants, 95% did not need any assistance to use the app, 74% confirmed that the PIA app made them feel better informed and more satisfied with their hospital stay, and 89% stated that they would like to re-use the PIA app and support the general use of medical apps in healthcare. Thus, we created an innovative digital health information tool, allowing targeted support for doctor-nurse-patient communication and offering great potential for patient support before and after surgery. Our study revealed that use of an app during the surgical hospital stay is readily accepted and benefits patients by acting as an additional informative tool.

BAP1 and PTEN mutations shape the immunological landscape of clear cell renal cell carcinoma and reveal the intertumoral heterogeneity of T cell suppression: a proof-of-concept study.

Clear cell renal cell carcinoma (ccRCC) is an immunologically vulnerable tumor entity, and immune checkpoint inhibitors are now widely used to treat patients with advanced disease. Whether and to what extent immune responses in ccRCC are shaped by genetic alterations, however, is only beginning to emerge. In this proof-of-concept study, we performed a detailed correlative analysis of the mutational and immunological landscapes in a series of 23 consecutive kidney cancer patients. We discovered that a high infiltration with CD8 + T cells was not dependent on the number of driver mutations but rather on the presence of specific mutational events, namely pathogenic mutations in PTEN or BAP1. This observation encouraged us to compare mechanisms of T cell suppression in the context of four different genetic patterns, i.e., the presence of multiple drivers, a PTEN or BAP1 mutation, or the absence of detectable driver mutations. We found that ccRCCs harboring a PTEN or BAP1 mutation showed the lowest level of Granzyme B positive tumor-infiltrating lymphocytes (TILs). A multiplex immunofluorescence analysis revealed a significant number of CD8 + TILs in the vicinity of CD68 + macrophages/monocytes in the context of a BAP1 mutation but not in the context of a PTEN mutation. In line with this finding, direct interactions between CD8 + TILs and CD163 + M2-polarized macrophages were found in BAP1-mutated ccRCC but not in tumors with other mutational patterns. While an absence of driver mutations was associated with more CD8 + TILs in the vicinity of FOXP3 + Tregs and CD68 + monocytes/macrophages, the presence of multiple driver mutations was, to our surprise, not found to be strongly associated with immunosuppressive mechanisms. Our results highlight the role of genetic alterations in shaping the immunological landscape of ccRCC. We discovered a remarkable heterogeneity of mechanisms that can lead to T cell suppression, which supports the need for personalized immune oncological approaches.

Contribution of Dynamic Contrast-enhanced and Diffusion MRI to PI-RADS for Detecting Clinically Significant Prostate Cancer.

Background Prostate Imaging Reporting and Data System (PI-RADS) version 2.0 requires multiparametric MRI of the prostate, including diffusion-weighted imaging (DWI) and dynamic contrast-enhanced (DCE) imaging sequences; however, the contribution of DCE imaging remains unclear. Purpose To assess whether DCE imaging in addition to apparent diffusion coefficient (ADC) and normalized T2 values improves PI-RADS version 2.0 for prediction of clinically significant prostate cancer (csPCa). Materials and Methods In this retrospective study, clinically reported PI-RADS lesions in consecutive men who underwent 3-T multiparametric MRI (T2-weighted, DWI, and DCE MRI) from May 2015 to September 2016 were analyzed quantitatively and compared with systematic and targeted MRI-transrectal US fusion biopsy. The normalized T2 signal (nT2), ADC measurement, mean early-phase DCE signal (mDCE), and heuristic DCE parameters were calculated. Logistic regression analysis indicated the most predictive DCE parameters for csPCa (Gleason grade group ≥2). Receiver operating characteristic parameter models were compared using the Obuchowski test. Recursive partitioning analysis determined ADC and mDCE value ranges for combined use with PI-RADS. Results Overall, 260 men (median age, 64 years [IQR, 58-69 years]) with 432 lesions (csPCa [n = 152] and no csPCa [n = 280]) were included. The mDCE parameter was predictive of csPCa when accounting for the ADC and nT2 parameter in the peripheral zone (odds ratio [OR], 1.76; 95% CI: 1.30, 2.44; P = .001) but not the transition zone (OR, 1.17; 95% CI: 0.81, 1.69; P = .41). Recursive partitioning analysis selected an ADC cutoff of 0.897 × 10-3 mm2/sec (P = .04) as a classifier for peripheral zone lesions with a PI-RADS score assessed on the ADC map (hereafter, ADC PI-RADS) of 3. The mDCE parameter did not differentiate ADC PI-RADS 3 lesions (P = .11), but classified lesions with ADC PI-RADS scores greater than 3 with low ADC values (less than 0.903 × 10-3 mm2/sec, P < .001) into groups with csPCa rates of 70% and 97% (P = .008). A lesion size cutoff of 1.5 cm and qualitative DCE parameters were not defined as classifiers according to recursive partitioning (P > .05). Conclusion Quantitative or qualitative dynamic contrast-enhanced MRI was not relevant for Prostate Imaging Reporting and Data System (PI-RADS) 3 lesion risk stratification, while quantitative apparent diffusion coefficient (ADC) values were helpful in upgrading PI-RADS 3 and PI-RADS 4 lesions. Quantitative ADC measurement may be more important for risk stratification than current methods in future versions of PI-RADS. © RSNA, 2022 Online supplemental material is available for this article See also the editorial by Goh in this issue.

Cavoatrial hypernephroma resection on cardiopulmonary bypass: Mild/normo-versus moderate hypothermia.

INTRODUCION: Renal cell carcinoma (RCC) is one of the most prevalent malignant tumors. It extends up into the systemic veins and right atrium. Surgical extraction of such extensions is usually carried out using cardiopulmonary bypass (CPB) with moderate hypothermic (MH) being frequently applied in order to obtain a clear surgical field. However, due to obvious disadvantages of hypothermia, approaches with mild/normothermia (NT) during CPB have also been established. The current study aims to compare the outcomes of patients undergoing RCC tumor and extensions resection using MH versus NT. MATERIAL AND METHODS: This is a retrospective, non-randomized study. All patients who underwent RCC tumor and extensions resection for stage III or IV (Staehler) RCC in a single center between 2006 and 2020 were included. During surgery, MH or NT were applied. CPB was realized using aortic and bicaval cannulation. We compared the procedural times, transfusion requirements and postoperative outcomes, respectively between the MH and NT groups. RESULTS: A total of 24 consecutive patients (n(NT) = 12, n(MH) = 12) were included in the study (median age NT 68.5 and MH 66.5). The study only showed a significant difference in heart-lung machine times (median CPB time NT 45.5 min and MH 110.0 min, p = 0.004). All other results, loss of drainage, administration of blood products, as well as the postoperative course and mortality were comparable in both groups. CONCLUSION: The results showed a high perioperative and long-term mortality. The perioperative course was similar after surgery with NT or MH. Therefore, NT which minimizes potential complications of MH should be preferred.

Hydronephrotic pelvic kidney mimicking urinary retention in an 18-year-old male.

We present a case of a hydronephrotic pelvic kidney in an 18-year-old male reporting about inability to void. Ultrasound showed a hypoechogenic mass mimicking a full urinary bladder. Anticipating urinary retention, a foley was inserted but no urin could be aspirated. Imaging showed a hydronephrotic pelvic kidney with no relevant function obstructing the urinary bladder and the contralateral ureter. Nephrectomy was performed and postoperative course was uneventful. A hydronephrotic pelvic kidney is a rare but important differential diagnosis in young men reporting lower abdominal pain and inability to void.

Expression of nectin-4 in papillary renal cell carcinoma.

BACKGROUND: Nectin-4 contributes to tumor proliferation, lymphangiogenesis and angiogenesis in malignant tumors and is an emerging target in tumor therapy. In renal cell carcinoma (RCC) VEGF-directed tyrosine kinase inhibitors and checkpoint inhibitors are currently treatments of choice. Enfortumab vedotin-ejf (EV) is an antibody drug conjugate that targets Nectin-4. The aim of our study was to investigate the expression of Nectin-4 in a large cohort of papillary RCC specimens. PATIENTS AND METHODS: Specimens were derived from the PANZAR consortium (Erlangen, Heidelberg, Herne, Homburg, Mainz, Mannheim, Marburg, Muenster, LMU Munich, TU Munich, and Regensburg). Clinical data and tissue samples from n = 190 and n = 107 patients with type 1 and 2 pRCC, respectively, were available. Expression of Nectin-4 was determined by immunohistochemistry (IHC). RESULTS: In total, Nectin-4 staining was moderately or strongly positive in of 92 (48.4%) of type 1 and 39 (36.4%) type 2 of pRCC cases. No associations between Nectin-4 expression and age at diagnosis, gender, grading, and TNM stage was found. 5 year overall survival rate was not statistically different in patients with Nectin-4 negative versus Nectin-4 positive tumors for the overall cohort and the pRCC type 2 subgroup, but higher in patient with Nectin-4 positive pRCC type 1 tumors compared to Nectin-4 negative tumors (81.3% vs. 67.8%, p = 0.042). CONCLUSION: Nectin-4 could not be confirmed as a prognostic marker in pRCC in general. Due to its high abundance on pRCC specimens Nectin-4 is an interesting target for therapeutical approaches e.g. with EV. Clinical trials are warranted to elucidate its role in the pRCC treatment landscape.

The Prognostic Impact of PD-L2 in Papillary Renal-Cell Carcinoma.

INTRODUCTION: Programmed death-1 ligand (PD-L1) has been often studied in different types of renal-cell carcinoma (RCC). For example, in clear-cell renal carcinoma it is well established that programmed death-1 receptor and PD-L1 are important prognostic markers. In contrast, the role of programmed death-2 ligand (PD-L2) as prognostic marker remains unclear. The aim of this study was to evaluate if PD-L2 expression could play a role as a prognostic marker for papillary RCC (pRCC). METHODS: The patients' sample collection was a joint collaboration of the PANZAR consortium. Patients' medical history and tumor specimens were collected from n = 240 and n = 128 patients with type 1 and 2 pRCC, respectively. Expression of PD-L2 was determined by immunohistochemistry. In total, PD-L2 staining was evaluable in 185 of 240 type 1 and 99 of 128 type 2 pRCC cases. RESULTS: PD-L2 staining was positive in 67 (36.2%) of type 1 and in 31 (31.3%) of type 2 pRCC specimens. The prevalence of PD-L2+ cells was significantly higher in high-grade type 1 tumors (p = 0.019) and in type 2 patients with metastasis (p = 0.002). Kaplan-Meier analysis disclosed significant differences in 5-year overall survival (OS) for patients with PD-L2- compared to PD-L2+ in pRCC type 1 of 88.4% compared to 73.6% (p = 0.039) and type 2 of 78.8% compared to 39.1% % (p < 0.001). However, multivariate analysis did not identify the presence of PD-L2+ cells neither in type 1 nor type 2 pRCC as an independent predictor of poor OS. DISCUSSION/CONCLUSION: PD-L2 expression did not qualify as an independent prognostic marker in pRCC. Future studies will have to determine whether anti-PD-L2-targeted treatment may play a role in pRCC and expression can potentially serve as a predictive marker for these therapeutic approaches.