Improving detection of carcinoma in situ in bladder cancer: urinary cytology vs the Xpert® BC Monitor.

OBJECTIVE: To investigate and compare the performance of urinary cytology and the Xpert BC Monitor test in the detection of bladder cancer in various clinically significant patient cohorts, including patients with carcinoma in situ (CIS), in a prospective multicentre setting, aiming to identify potential applications in clinical practice. PATIENTS AND METHODS: A total of 756 patients scheduled for transurethral resection of bladder tumour (TURBT) were prospectively screened between July 2018 and December 2020 at six German University Centres. Central urinary cytology and Xpert BC Monitor tests were performed prior to TURBT. The diagnostic performance of urinary cytology and the Xpert BC Monitor was evaluated according to sensitivity (SN), specificity (SC), negative predictive value (NPV) and positive predictive value (PPV). Statistical comparison of urinary cytology and the Xpert BC Monitor was conducted using the McNemar test. RESULTS: Of 756 screened patients, 733 (568 male [78%]; median [interquartile range] age 72 [62-79] years) were included. Bladder cancer was present in 482 patients (65.8%) with 258 (53.5%) high-grade tumours. Overall SN, SC, NPV and PPV were 39%, 93%, 44% and 92% for urinary cytology, and 75%, 69%, 59% and 82% for the Xpert BC Monitor. In patients with CIS (concomitant or solitary), SN, SC, NPV and PPV were 59%, 93%, 87% and 50% for urinary cytology, and 90%, 69%, 95% and 50% for the Xpert BC Monitor. The Xpert BC Monitor missed four tumours (NPV = 98%) in patients with solitary CIS, while potentially avoiding 63.3% of TURBTs in inconclusive or negative cystoscopy and a negative Xpert result. CONCLUSION: Positive urinary cytology may indicate bladder cancer and should be taken seriously. The Xpert BC Monitor may represent a useful diagnostic tool for correctly identifying patients with solitary CIS and unsuspicious or inconclusive cystoscopy.

[Should we all switch to en-bloc resection of bladder tumours?] / Sollten wir alle zur En Bloc Resektion von Blasentumoren wechseln?

In En-Bloc Resection of Bladder Tumours (ERBT), tumours are not removed in fragments, but are dissected in one layer and, if possible, extracted in one piece. This method represents a significant shift in the surgical management of non-muscle-invasive bladder tumours, providing multiple benefits over the traditional transurethral resection of the bladder (TUR-B). The histological analysis of ERBT specimens is more accurate, enhancing diagnostic precision. Additionally, the presence of detrusor muscle in ERBT specimens is more frequent, indicating a more complete removal of the tumours. Recent years have seen the consolidation of a robust evidence base emphasizing the advantages of ERBT. Notably, a multicentric, prospective randomized trial has recently revealed a significant reduction in recurrence rates at 12 months follow-up compared with TUR-B. Experienced endourologists should explore this technique, as it may soon become the standard of care. The technique's elegance and effectiveness make it too important to be ignored.

Peritoneal Flap for Lymphocele Prophylaxis Following Robotic-assisted Radical Prostatectomy with Lymph Node Dissection: The Randomised Controlled Phase 3 PELYCAN Trial.

BACKGROUND: Symptomatic lymphoceles (SLCs) after transperitoneal robotic-assisted radical prostatectomy with pelvic lymph node dissection (PLND) are common. Evidence from randomised controlled trials (RCTs) on the impact of peritoneal flaps (PFs) on lymphocele (LC) reduction is inconclusive. OBJECTIVE: To show that addition of PFs leads to a reduction of postoperative SLCs. DESIGN, SETTING, AND PARTICIPANTS: An investigator-initiated, prospective, parallel, double-blinded, adaptive, phase 3 RCT was conducted. Recruitment took place from September 2019 until December 2021; 6-month written survey-based follow-up was recorded. Stratification was carried out according to potential LC risk factors (extended PLND, diabetes mellitus, and anticoagulation) and surgeons; 1:1 block randomisation was used. Surgeons were informed about allocation after completion of the last surgical step. INTERVENTION: To create PFs, the ventral peritoneum was incised bilaterally and fixated to the pelvic floor. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary endpoint was SLCs. Secondary endpoints included asymptomatic lymphoceles (ALCs), perioperative parameters, and postoperative complications. RESULTS AND LIMITATIONS: In total, 860 men were screened and 551 randomised. Significant reductions of SLCs (from 9.1% to 3.7%, p = 0.005) and ALCs (27.2% to 10.3%, p < 0.001) over the follow-up period of 6 mo were observed in the intention-to-treat analysis. Operating time was 11 min longer (p < 0.001) in the intervention group; no significant differences in amount (80 vs 103, p = 0.879) and severity (p = 0.182) of postoperative complications (excluding LCs) were observed. The survey-based follow-up might be a limitation. CONCLUSIONS: This is the largest RCT evaluating PF creation for LC prevention and met its primary endpoint, the reduction of SLCs. The results were consistent among all subgroup analyses including ALCs. Owing to the subsequent reduction of burden for patients and the healthcare system, establishing PFs should become the new standard of care. PATIENT SUMMARY: A new technique-creation of bilateral peritoneal flaps-was added to the standard procedure of robotic-assisted prostatectomy for lymph node removal. It was safe and decreased lymphocele development, a common postoperative complication and morbidity. Hence, it should become a standard procedure.

Robotic-assisted versus manual Uro Dyna-CT-guided puncture in an ex-vivo kidney phantom.

INTRODUCTION AND OBJECTIVES: Challenging percutaneous renal punctures to gain access to the kidney requiring guidance by cross-sectional imaging. To test the feasibility of robotic-assisted CT-guided punctures (RP) and compare them with manual laser-guided punctures (MP) with Uro Dyna-CT (Siemens Healthcare Solutions, Erlangen, Germany). MATERIAL AND METHODS: The silicon kidney phantom contained target lesions of three sizes. RP were performed using a robotic assistance system (guidoo, BEC GmbH, Pfullingen, Germany) with a robotic arm (LBR med R800, KUKA AG, Augsburg, Germany) and a navigation software with a cone-beam-CT Artis zeego (Siemens Healthcare GmbH, Erlangen, Germany). MP were performed using the syngo iGuide Uro-Dyna Artis Zee Ceiling CT (Siemens Healthcare Solutions). Three urologists with varying experience performed 20 punctures each. Success rate, puncture accuracy, puncture planning time (PPT), and needle placement time (NPT) were measured and compared with ANOVA and Chi-Square Test. RESULTS: One hundred eighteen punctures with a success rate of 100% for RP and 78% for MP were included. Puncture accuracy was significantly higher for RP. PPT (RP: 238 ± 90s, MP: 104 ± 21s) and NPT (RP: 128 ± 40s, MP: 81 ± 18s) were significantly longer for RP. The outcome variables did not differ significantly with regard to levels of investigators' experience. CONCLUSION: The accuracy of RP was superior to that of MP. This study paves the way for first in-human application of this robotic puncture system.

Framework for a living systematic review and meta-analysis for the surgical treatment of bladder cancer: introducing EVIglance to urology.

Background: Knowledge of current and ongoing studies is critical for identifying research gaps and enabling evidence-based decisions for individualized treatment. However, the increasing number of scientific publications poses challenges for healthcare providers and patients in all medical fields to stay updated with the latest evidence. To overcome these barriers, we aim to develop a living systematic review and open-access online evidence map of surgical therapy for bladder cancer (BC), including meta-analyses. Methods: Following the guidelines provided in the Cochrane Handbook for Systematic Reviews of Interventions and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Statement, a systematic literature search on uro-oncological therapy in BC will be performed across various literature databases. Within the scope of a meta-analysis and living systematic review, relevant randomized controlled trials will be identified. Data extraction and quantitative analysis will be conducted, along with a critical appraisal of the quality and risk of bias of each study. The available research evidence will be entered into an open-access framework (www.evidencemap.surgery) and will also be accessible via the EVIglance app. Regular semi-automatic updates will enable the implementation of a real-living review concept and facilitate resource-efficient screening. Discussion: A regularly updated evidence map provides professionals and patients with an open-access knowledge base on the current state of research, allowing for decision-making based on recent evidence. It will help identify an oversupply of evidence, thus avoiding redundant work. Furthermore, by identifying research gaps, new hypotheses can be formulated more precisely, enabling planning, determination of sample size, and definition of endpoints for future trials.

Xpert bladder cancer monitor to predict the need for a second TURB (MoniTURB trial).

To determine whether Xpert bladder cancer monitor, a noninvasive PCR-based biomarker test, can predict the need for 2nd transurethral resection of the bladder (TURB) better than clinical assessment. Patients scheduled for TURB were prospectively screened. After initial TURB, patients were assigned to 2nd TURB or follow-up cystoscopy at 3 months (FU) by clinicians' discretion. Central urine cytology and Xpert monitor tests were performed prior to the 1st TURB and 2nd TURB or FU, respectively. Statistical analysis to compare clinical assessment and Xpert monitor comprised sensitivity (SENS), specificity (SPEC), NPV and PPV. Of 756 screened patients, 171 were included (114 with 2nd TURB, 57 with FU). Residual tumors were detected in 34 patients who underwent 2nd TURB, and recurrent tumors were detected in 2 patients with FU. SENS and SPEC of Xpert monitor were 83.3% and 53.0%, respectively, PPV was 32.6% and NPV was 92.1%. Clinical risk assessment outperformed Xpert monitor. In patients with pTa disease at initial TURB, Xpert monitor revealed a NPV of 96%. Xpert monitor was not superior than clinical assessment in predicting the need for 2nd TURB. It might be an option to omit 2nd TURB for selected patients with pTa disease.

Reinvestigating the clinical relevance of the m6A writer METTL3 in urothelial carcinoma of the bladder.

METTL3 is the major writer of N6-Methyladenosine (m6A) and has been associated with controversial roles in cancer. This is best illustrated in urothelial carcinoma of the bladder (UCB), where METTL3 was described to have both oncogenic and tumor-suppressive functions. Here, we reinvestigated the role of METTL3 in UCB. METTL3 knockout reduced the oncogenic phenotype and m6A levels of UCB cell lines. However, complete depletion of METTL3/m6A was not achieved due to selection of cells expressing alternative METTL3 isoforms. Systematic vulnerability and inhibitor response analyses suggested that uroepithelial cells depend on METTL3 for viability. Furthermore, expression and survival analyses of clinical data revealed a complex role for METTL3 in UCB, with decreased m6A mRNA levels in UCB tumors. Our results suggest that METTL3 expression may be a suitable diagnostic UCB biomarker, as the enzyme promotes UCB formation. However, the suitability of the enzyme as a therapeutic target should be evaluated carefully.

Getting specific: participation preference in urooncological decision-making.

BACKGROUND: Shared decision-making is the gold standard for good clinical practice, and thus, psychometric instruments have been established to assess patients' generic preference for participation (e.g., the Autonomy Preference Index, API). However, patients' preferences may vary depending on the specific disease and with respect to the specific decision context. With a modified preference index (API-Uro), we assessed patients' specific participation preference in preference-sensitive decisions pertaining to urological cancer treatments and compared this with their generic participation preference. METHODS: In Study 1, we recruited (N = 469) urological outpatients (43.1% urooncological) at a large university hospital. Participation preference was assessed with generic measures (API and API case vignettes) and with the disease-specific API-Uro (urooncological case vignettes describing medical decisions of variable difficulty). A polychoric exploratory factor analysis was used to establish factorial validity and reduce items. In Study 2, we collected data from N = 204 bladder cancer patients in a multicenter study to validate the factorial structure with confirmatory factor analysis. Differences between the participation preference for different decision contexts were analyzed. RESULTS: Study 1: Scores on the specific urooncological case vignettes (API-Uro) correlated with the generic measure (r = .44) but also provided incremental information. Among the disease-specific vignettes of the API-Uro, there were two factors with good internal consistency (α ≥ .8): treatment versus diagnostic decisions. Patients desired more participation for treatment decisions (77.8%) than for diagnostic decisions (22%), χ2(1) = 245.1, p ≤ .001. Study 2: Replicated the correlation of the API-Uro with the API (r = .39) and its factorial structure (SRMR = .08; CFI = .974). Bladder cancer patients also desired more participation for treatment decisions (57.4%) than for diagnostic decisions (13.3%), χ²(1) =84, p ≤ .001. CONCLUSIONS: The desire to participate varies between treatment versus diagnostic decisions among urological patients. This underscores the importance of assessing participation preference for specific contexts. Overall, the new API-Uro has good psychometric properties and is well suited to assess patients' preferences. In routine care, measures of participation preference for specific decision contexts may provide incremental, allowing clinicians to better address their patients' individual needs.

A self-supervised vision transformer to predict survival from histopathology in renal cell carcinoma.

PURPOSE: To develop and validate an interpretable deep learning model to predict overall and disease-specific survival (OS/DSS) in clear cell renal cell carcinoma (ccRCC). METHODS: Digitised haematoxylin and eosin-stained slides from The Cancer Genome Atlas were used as a training set for a vision transformer (ViT) to extract image features with a self-supervised model called DINO (self-distillation with no labels). Extracted features were used in Cox regression models to prognosticate OS and DSS. Kaplan-Meier for univariable evaluation and Cox regression analyses for multivariable evaluation of the DINO-ViT risk groups were performed for prediction of OS and DSS. For validation, a cohort from a tertiary care centre was used. RESULTS: A significant risk stratification was achieved in univariable analysis for OS and DSS in the training (n = 443, log rank test, p < 0.01) and validation set (n = 266, p < 0.01). In multivariable analysis, including age, metastatic status, tumour size and grading, the DINO-ViT risk stratification was a significant predictor for OS (hazard ratio [HR] 3.03; 95%-confidence interval [95%-CI] 2.11-4.35; p < 0.01) and DSS (HR 4.90; 95%-CI 2.78-8.64; p < 0.01) in the training set but only for DSS in the validation set (HR 2.31; 95%-CI 1.15-4.65; p = 0.02). DINO-ViT visualisation showed that features were mainly extracted from nuclei, cytoplasm, and peritumoural stroma, demonstrating good interpretability. CONCLUSION: The DINO-ViT can identify high-risk patients using histological images of ccRCC. This model might improve individual risk-adapted renal cancer therapy in the future.

An m6A-Driven Prognostic Marker Panel for Renal Cell Carcinoma Based on the First Transcriptome-Wide m6A-seq.

To date, only a single transcriptome-wide m6A sequencing study of clear cell renal cell carcinoma (ccRCC) has been reported, with no validation so far. Herein, by TCGA analysis of the KIRC cohort (n = 530 ccRCC; n = 72 normal), an external expression validation of 35 preidentified m6A targets was performed. Further in-depth expression stratification enabled assessment of m6A-driven key targets. Overall survival (OS) analysis and gene set enrichment analyses (GSEA) were conducted to assess their clinical and functional impact on ccRCC. In the hyper-up cluster significant upregulation was confirmed for NDUFA4L2, NXPH4, SAA1, and PLOD2 (40%) and in the hypo-up cluster for FCHSD1 (10%). Significant downregulation was observed for UMOD, ANK3, and CNTFR (27.3%) in the hypo-down cluster and for CHDH (25%) in the hyper-down cluster. In-depth expression stratification showed consistent dysregulation in ccRCC only for 11.67%: NDUFA4L2, NXPH4, and UMOD (NNU-panel). Patients with strong NNU panel dysregulation had significantly poorer OS (p = 0.0075). GSEA identified 13 associated and significantly upregulated gene sets (all p-values < 0.5; FDR < 0.25). External validation of the only available m6A sequencing in ccRCC consistently reduced dysregulated m6A-driven targets on the NNU panel with highly significant effects on OS. Epitranscriptomics are a promising target for developing novel therapies and for identifying prognostic markers for daily clinical practice.

When attitudes and beliefs get in the way of shared decision-making: A mediation analysis of participation preference.

INTRODUCTION: Certain sociodemographic characteristics (e.g., older age) have previously been identified as barriers to patients' participation preference in shared decision-making (SDM). We aim to demonstrate that this relationship is mediated by the perceived power imbalance that manifests itself in patients' negative attitudes and beliefs about their role in decision-making. METHODS: We recruited a large sample (N = 434) of outpatients with a range of urological diagnoses (42.2% urooncological). Before the medical consultation at a university hospital, patients completed the Patients' Attitudes and Beliefs Scale and the Autonomy Preference Index. We evaluated attitudes as a mediator between sociodemographic factors and participation preference in a path model. RESULTS: We replicated associations between relevant sociodemographic factors and participation preference. Importantly, attitudes and beliefs about one's own role as a patient mediated this relationship. The mediation path model explained a substantial proportion of the variance in participation preference (27.8%). Participation preferences and attitudes did not differ for oncological and nononcological patients. CONCLUSION: Patients' attitudes and beliefs about their role determine whether they are willing to participate in medical decision-making. Thus, inviting patients to participate in SDM should encompass an assessment of their attitudes and beliefs. Importantly, negative attitudes may be accessible to change. Unlike stable sociodemographic characteristics, such values are promising targets for interventions to foster more active participation in SDM. PATIENT OR PUBLIC CONTRIBUTION: This study was part of a larger project on implementing SDM in urological practice. Several stakeholders were involved in the design, planning and conduction of this study, for example, three authors are practising urologists, and three are psychologists with experience in patient care. In addition, the survey was piloted with patients, and their feedback was integrated into the questionnaire. The data presented in this study is based on patients' responses. Results may help to empower our patients.

Robotic-assisted Versus Laparoscopic Versus Open Radical Cystectomy-A Systematic Review and Network Meta-analysis of Randomized Controlled Trials.

CONTEXT: Multiple randomized controlled trials (RCTs) on the three approaches of radical cystectomy (robotic assisted [RARC], laparoscopic [LRC], and open [ORC]) have been published recently. OBJECTIVE: To perform a systematic review and network meta-analysis (NMA) of RCTs comparing RARC, LRC, and ORC, with the primary outcomes being overall survival (OS) and recurrence-free survival (RFS). EVIDENCE ACQUISITION: A search of the Cochrane Central Register of Controlled Trials, MEDLINE, and Web of Science (last search: 20/05/2022) was performed. The prospectively registered protocol stated that a NMA of the primary outcomes would be performed only if there was sufficient evidence to compare all three approaches. In case of insufficient evidence, a comparison between the two most common approaches would be performed. The risk of bias and certainty of evidence (CoE) via the Grading of Recommendations Assessment, Development, and Evaluation approach was assessed for direct evidence and the most common comparison. EVIDENCE SYNTHESIS: Ten trials were identified. There was insufficient evidence for a NMA of all approaches for the primary outcomes. The meta-analysis of RARC and ORC showed no differences in OS (hazard ratio (HR) [confidence interval (CI): 0.98 [0.73-1.30]) and RFS (HR [CI]: 0.99 [0.75-1.31]) with moderate CoE. The secondary outcomes showed lower rates of transfusions (p < 0.01) and longer operating time (p < 0.01) with high CoE for RARC compared with ORC. There were no differences for quality of life, positive margins, length of hospital stay, or major complications (all p > 0.05). CONCLUSIONS: There are no differences in OS and RFS between RARC and ORC, with moderate CoE. Clinicians should likely apply the approach with which they can reach the highest case volume and in which they have the most experience. PATIENT SUMMARY: We looked at the difference between three types (robotic assisted, laparoscopic, and open) of operating techniques for radical cystectomy. The data showed no significant differences in OS between the robotic-assisted and the open technique, while enough data were not available to make a comparison with conventional laparoscopic surgery.

External validation of yonsei nomogram predicting chronic kidney disease development after partial nephrectomy: An international, multicenter study.

OBJECTIVE: To externally validate Yonsei nomogram. METHODS: From 2000 through 2018, 3526 consecutive patients underwent on-clamp PN for cT1 renal masses at 23 centers were included. All patients had two kidneys, preoperative eGFR ≥60 ml/min/1.73 m2, and a minimum follow-up of 12 months. New-onset CKD was defined as upgrading from CKD stage I or II into CKD stage ≥III. We obtained the CKD-free progression probabilities at 1, 3, 5, and 10 years for all patients by applying the nomogram found at https://eservices.ksmc.med.sa/ckd/. Thereafter, external validation of Yonsei nomogram for estimating new-onset CKD stage ≥III was assessed by calibration and discrimination analysis. RESULTS AND LIMITATION: Median values of patients' age, tumor size, eGFR and follow-up period were 47 years (IQR: 47-62), 3.3 cm (IQR: 2.5-4.2), 90.5 ml/min/1.73 m2 (IQR: 82.8-98), and 47 months (IQR: 27-65), respectively. A total of 683 patients (19.4%) developed new-onset CKD. The 5-year CKD-free progression rate was 77.9%. Yonsei nomogram demonstrated an AUC of 0.69, 0.72, 0.77, and 0.78 for the prediction of CKD stage ≥III at 1, 3, 5, and 10 years, respectively. The calibration plots at 1, 3, 5, and 10 years showed that the model was well calibrated with calibration slope values of 0.77, 0.83, 0.76, and 0.75, respectively. Retrospective database collection is a limitation of our study. CONCLUSIONS: The largest external validation of Yonsei nomogram showed good calibration properties. The nomogram can provide an accurate estimate of the individual risk of CKD-free progression on long-term follow-up.

Prospective, Randomized Comparative Evaluation of a Novel Hands-On Endourology Training Curriculum.

INTRODUCTION: The aim of this randomised prospective trial was to evaluate a novel hands-on endourological training programme (HTP) and compare it to the standard endourological colloquium (SC). METHODS: A new HTP was created based on a sequence of theoretical, video-based, and practical elements emphasising contemporary teaching methods. An existing SC in which live endourological operations were attended served as a comparison. Medical students were enrolled in a ratio of 1:2 (SC:HTP). Objective knowledge questionnaires (5 questions, open answers) and subjective Likert-type questionnaires (rating 1-3 vs. 4-5) were used for evaluation. Primary endpoint was urological knowledge transfer; secondary endpoints were learning effects, progression, and urological interest. RESULTS: 167 students (SC n = 52, HTP n = 115) were included. The knowledge assessment showed a significant increase in knowledge transfer benefitting the HTP on all 5 surveyed items (mean: n = 4/5/4/3/2 vs. n = 2/3/1/1, p < 0.0001). Interest and duration of the course were rated significantly more positively by HTP students (100.0/95.0% vs. 85.0/70.0%, p < 0.0001). The HTP students were significantly more confident in performing a cystoscopy independently (HTP 43.5% vs. SC 11.5%, p < 0.0001) and significantly claimed more often to have gained interdisciplinary and urological skills during the course (HTP 90.0/96.5% vs. SC 23.1/82.7%, p < 0.0001/p = 0.003). HTP students were also more likely to take the course again (HTP 98.2% vs. SC 59.6%, p < 0.0001). CONCLUSION: Modifying endourological teaching towards hands-on teaching resulted in stronger course interest, greater confidence regarding endourologic procedures, and significantly increased urologic knowledge transfer.

Systemic inflammatory biomarkers as predictive and prognostic factors in men with metastatic castration-refractory prostate cancer treated with docetaxel therapy: a comprehensive analysis in a German real-world cohort.

PURPOSE: Advances in therapy of metastatic castration-refractory prostate cancer (mCRPC) resulted in more therapeutic options and led to a higher need of predictive/prognostic biomarkers. Systemic inflammatory biomarkers could provide the basis for personalized treatment selection. This study aimed to assess the modified Glasgow Prognostic Score (mGPS), the neutrophile-to-lymphocyte ratio (NLR), the platelet-to-lymphocyte ratio (PLR) and the systemic immune-inflammation index (SII) in men with mCRPC under docetaxel. METHODS: Patients with mCRPC and taxane chemotherapy at a tertiary care centre between 2010 and 2019 were screened retrospectively. The biomarkers mGPS, NLR, PLR and SII were assessed and analyzed for biochemical/radiologic response and survival. RESULTS: We included 118 patients. Of these, 73 (61.9%) had received docetaxel as first-line, 31 (26.2%) as second-line and 14 (11.9%) as third-line treatment. For biochemical response, mGPS (odds ratio (OR) 0.54, p = 0.04) and PLR (OR 0.63, p = 0.04) were independent predictors in multivariable analysis. SII was significant in first-line cohort only (OR 0.29, p = 0.02). No inflammatory marker was predictive for radiologic response. In multivariable analysis, mGPS and NLR (hazard ratio (HR) 1.71 and 1.12, both p < 0.01) showed significant association with OS in total cohort and mGPS in the first-line cohort (HR 2.23, p < 0.01). Haemoglobin (Hb) and alkaline phosphatase (AP) showed several significant associations regarding 1 year, 3 year, OS and biochemical/radiologic response. CONCLUSIONS: Pre-treatment mGPS seems a promising prognostic biomarker. A combination of mGPS, NLR and further routine markers (e.g., Hb and AP) could yield optimized stratification for treatment selection. Further prospective and multicentric assessment is needed.

Patient Compliance in Assessing Electronic Patient-Reported Outcome Measures after Urologic Surgery.

INTRODUCTION: This study aimed to assess patient compliance with a newly established electronic patient-reported outcome measure (ePROM) system after urologic surgery and to identify influencing factors. METHODS: Digital surveys were provided to patients undergoing cystectomy, radical or partial nephrectomy, or transurethral resection of bladder tumor via a newly established ePROM system. Participants received a baseline survey preoperatively and several follow-up surveys postoperatively. Multivariable regression analysis was performed to identify factors predicting compliance. RESULTS: Of N = 435 eligible patients, n = 338 completed the baseline survey (78.0%). Patients who did not participate were significantly more likely male (p = 0.004) and older than 70 years (p = 0.005). Overall, 206/337 patients (61.3%) completed the survey at 1-month, 167/312 (53.5%) at 3-month, and 142/276 (51.4%) at 6-month follow-up. Lower baseline quality of life (odds ratio: 2.27; p = 0.004) was a significant predictor for dropout at 1-month follow-up. Low educational level was significantly associated with low compliance at 3- (OR: 1.92; p = 0.01) and 6-month follow-up (OR: 2.88; p < 0.001). CONCLUSION: Acceptable compliance rates can be achieved with ePROMs following urologic surgery. Several factors influence compliance and should be considered when setting-up ePROM surveys.

Changes in neutrophile-to-lymphocyte ratio as predictive and prognostic biomarker in metastatic prostate cancer treated with taxane-based chemotherapy.

OBJECTIVES: To assess the predictive and prognostic value of changes in longitudinal neutrophile-to-lymphocyte (NLR) ratios in men receiving taxane-based chemotherapy for metastatic prostate cancer (PC). METHODS: Retrospective, unicentric cohort study of patients treated with either docetaxel for metastatic hormone-sensitive PC (mHSPC) or docetaxel or cabazitaxel for metastatic castration-refractory PC (mCRPC) at a tertiary referral hospital between 2010 and 2019. NLR ratios were calculated for each cycle. Next, slopes over the first three (NLR3) and over six cycles (NLR6) were calculated and analysed for biochemical/radiologic response and survival. RESULTS: A total of 36 mHSPC (docetaxel), 118 mCRPC (docetaxel) and 38 mCRPC (cabazitaxel) patients were included. NLR3 was significantly associated with 1-year-survival, radiographic and biochemical response in mCRPC (docetaxel) in uni- and multivariable analyses. In mCRPC (docetaxel), positive NLR3s were associated with favourable 1-year-survival. CONCLUSION: This study demonstrated NLR3 as a prognostic marker in men receiving docetaxel for mCRPC. NLR3 might be a clinical tool to reflect the individual's response to taxane-based chemotherapy. Thereby, NLR3 could complement existing biomarkers and help to early identify treatment failure before complications arise. Further prospective and multicentric studies are needed to extend and confirm the presented results.

Ureterovesical Anastomosis Complications in Kidney Transplantation: Definition, Risk Factor Analysis, and Prediction by Quantitative Fluorescence Angiography with Indocyanine Green.

Ureteral stenosis and urinary leakage are relevant problems after kidney transplantation. A standardized definition of ureterovesical anastomosis complications after kidney transplantation has not yet been established. This study was designed to demonstrate the predictive power of quantitative indocyanine green (ICG) fluorescence angiography. This bicentric historic cohort study, conducted between November 2015 and December 2019, included 196 kidney transplantations. The associations between quantitative perfusion parameters of near-infrared fluorescence angiography with ICG and the occurrence of different grades of ureterovesical anastomosis complications in the context of donor, recipient, periprocedural, and postoperative characteristics were evaluated. Post-transplant ureterovesical anastomosis complications occurred in 18%. Complications were defined and graded into three categories. They were associated with the time on dialysis (p = 0.0025), the type of donation (p = 0.0404), and the number of postoperative dialysis sessions (p = 0.0173). Median ICG ingress at the proximal ureteral third was 14.00 (5.00-33.00) AU in patients with and 23.50 (4.00-117.00) AU in patients without complications (p = 0.0001, cutoff: 16 AU, sensitivity 70%, specificity 70%, AUC = 0.725, p = 0.0011). The proposed definition and grading of post-transplant ureterovesical anastomosis complications is intended to enable valid comparisons between studies. ICG Fluorescence angiography allows intraoperative quantitative assessment of ureteral microperfusion during kidney transplantation and is able to predict the incidence of ureterovesical anastomosis complications. Registration number: NCT-02775838.

Deep learning can predict survival directly from histology in clear cell renal cell carcinoma.

For clear cell renal cell carcinoma (ccRCC) risk-dependent diagnostic and therapeutic algorithms are routinely implemented in clinical practice. Artificial intelligence-based image analysis has the potential to improve outcome prediction and thereby risk stratification. Thus, we investigated whether a convolutional neural network (CNN) can extract relevant image features from a representative hematoxylin and eosin-stained slide to predict 5-year overall survival (5y-OS) in ccRCC. The CNN was trained to predict 5y-OS in a binary manner using slides from TCGA and validated using an independent in-house cohort. Multivariable logistic regression was used to combine of the CNNs prediction and clinicopathological parameters. A mean balanced accuracy of 72.0% (standard deviation [SD] = 7.9%), sensitivity of 72.4% (SD = 10.6%), specificity of 71.7% (SD = 11.9%) and area under receiver operating characteristics curve (AUROC) of 0.75 (SD = 0.07) was achieved on the TCGA training set (n = 254 patients / WSIs) using 10-fold cross-validation. On the external validation cohort (n = 99 patients / WSIs), mean accuracy, sensitivity, specificity and AUROC were 65.5% (95%-confidence interval [CI]: 62.9-68.1%), 86.2% (95%-CI: 81.8-90.5%), 44.9% (95%-CI: 40.2-49.6%), and 0.70 (95%-CI: 0.69-0.71). A multivariable model including age, tumor stage and metastasis yielded an AUROC of 0.75 on the TCGA cohort. The inclusion of the CNN-based classification (Odds ratio = 4.86, 95%-CI: 2.70-8.75, p < 0.01) raised the AUROC to 0.81. On the validation cohort, both models showed an AUROC of 0.88. In univariable Cox regression, the CNN showed a hazard ratio of 3.69 (95%-CI: 2.60-5.23, p < 0.01) on TCGA and 2.13 (95%-CI: 0.92-4.94, p = 0.08) on external validation. The results demonstrate that the CNN's image-based prediction of survival is promising and thus this widely applicable technique should be further investigated with the aim of improving existing risk stratification in ccRCC.

Complementary roles of surgery and systemic treatment in clear cell renal cell carcinoma.

Standard-of-care management of renal cell carcinoma (RCC) indisputably relies on surgery for low-risk localized tumours and systemic treatment for poor-prognosis metastatic disease, but a grey area remains, encompassing high-risk localized tumours and patients with metastatic disease with a good-to-intermediate prognosis. Over the past few years, results of major practice-changing trials for the management of metastatic RCC have completely transformed the therapeutic options for this disease. Treatments targeting vascular endothelial growth factor (VEGF) have been the mainstay of therapy for metastatic RCC in the past decade, but the advent of immune checkpoint inhibitors has revolutionized the therapeutic landscape in the metastatic setting. Results from several pivotal trials have shown a substantial benefit from the combination of VEGF-directed therapy and immune checkpoint inhibition, raising new hopes for the treatment of high-risk localized RCC. The potential of these therapeutics to facilitate the surgical extirpation of the tumour in the neoadjuvant setting or to improve disease-free survival in the adjuvant setting has been investigated. The role of surgery for metastatic RCC has been redefined, with results of large trials bringing into question the paradigm of upfront cytoreductive nephrectomy, inherited from the era of cytokine therapy, when initial extirpation of the primary tumour did show clinical benefits. The potential benefits and risks of deferred surgery for residual primary tumours or metastases after partial response to checkpoint inhibitor treatment are also gaining interest, considering the long-lasting effects of these new drugs, which encourages the complete removal of residual masses.