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Purpose Magnetic resonance imaging (MRI)/ultrasound-fusion prostate biopsy (FB) comprises multiple steps each of which can cause alterations in targeted biopsy (TB) accuracy leading to false-negative results. The aim was to assess the inter-operator variability of software-based fusion TB by targeting the same MRI-lesions by different urologists. Methods In this prospective study, 142 patients eligible for analysis underwent software-based FB. TB of all lesions (n = 172) were carried out by two different urologists per patient (n = 31 urologists). We analyzed the number of mismatches [overall prostate cancer (PCa), clinically significant PCa (csPCa) and non-significant PCa (nsPCa)] between both performed TB per patient. In addition we evaluated factors contributing to inter-operator variability by uni- and multivariable analyses. Results In 11.6% of all MRI-lesions (10.6% of all patients) there was a mismatch between TB1 and TB2 in terms of overall prostate cancer (PCa detection. Regarding csPCa, patient-based mismatch occurred in 14.8% (n = 21). Overall PCa and csPCa detection rate of TB1 and TB2 did not differ significantly on a per-patient and per-lesion level. Analyses revealed a smaller lesion size as predictive for mismatches (OR 9.19, 95% CI 2.02–41.83, p Conclusion Reproducibility and precision of targeting particularly small lesions is still limited although using software-based FB. Further improvements in image-fusion, segmentation, needle-guidance, and automatization are necessary.

Diagnostic and prognostic biomarkers in localized prostate cancer (PC) are insufficient. Treatment stratification relies on prostate-specific antigen, clinical tumor staging and International Society of Urological Pathology (ISUP) grading, whereas molecular profiling remains unused. Integrins (ITG) have an important function in bidirectional signaling and are associated with progression, proliferation, perineural invasion, angiogenesis, metastasis, neuroendocrine differentiation, and a more aggressive disease phenotype in PC. However, ITG subunit expression in localized PC and their utility as prognostic biomarkers has not yet been analyzed. This study aimed to fill this gap and provide a comprehensive overview of ITG expression as well as ITG utility as biomarkers.The Cancer Genome Atlas (TCGA) and the Memorial Sloan Kettering Cancer Center (MSKCC) prostate adenocarcinoma cohorts were analyzed regarding ITG expression in correlation to ISUP, N- and American Joint Committee on Cancer (AJCC) stage and were correlated with disease-free survival (DFS). Statistical tests used included the Mann-Whitney U-test, logrank test and uni- and multivariable cox regression analyses.After grouping for ISUP (1 and 2 vs. 3-5), N0 vs. N1 and AJCC stage (≤2 vs. ≥3), multiple ITGs showed significant expression differences. The most consistent results were observed for ITGα4, ITGαX, ITGα11, ITGβ2 and ITGα2. In multivariable cox regression, ITGα2, ITGα10, ITGαD, ITGαB2 (TCGA), ITGα11 and ITGβ4 (MSKCC) were independent predictors of DFS.The utility of ITGs as PC biomarkers was herein shown.

Artificial intelligence (AI) has been successfully applied for automatic tumor detection and grading in histopathological image analysis in urologic oncology. The aim of this review was to assess the applicability of these approaches in image-based oncological outcome prediction.A systematic literature search was conducted using the databases MEDLINE through PubMed and Web of Science up to April 20, 2021. Studies investigating AI approaches to determine the risk of recurrence, metastasis, or survival directly from HE-stained tissue sections in prostate, renal cell or urothelial carcinoma were included. Characteristics of the AI approach and performance metrics were extracted and summarized. Risk of bias (RoB) was assessed using the PROBAST tool.16 studies yielding a total of 6658 patients and reporting on 17 outcome predictions were included. Six studies focused on renal cell, six on prostate and three on urothelial carcinoma while one study investigated renal cell and urothelial carcinoma. Handcrafted feature extraction was used in five, a convolutional neural network (CNN) in six and a deep feature extraction in four studies. One study compared a CNN with handcrafted feature extraction. In seven outcome predictions, a multivariable comparison with clinicopathological parameters was reported. Five of them showed statistically significant hazard ratios for the AI's model's-prediction. However, RoB was high in 15 outcome predictions and unclear in two.The included studies are promising but predominantly early pilot studies, therefore primarily highlighting the potential of AI approaches. Additional well-designed studies are needed to assess the actual clinical applicability.

Purpose To validate a German translation of the convalescence and recovery evaluation (CARE) as an electronic patient-reported outcome measure (ePROM) and use it to assess recovery after major urological surgery. Methods The CARE questionnaire was provided to patients scheduled for major urological surgery preoperatively, at discharge and 6 weeks postoperatively, using an ePROM system. Cronbach’s alpha, inter-scale correlations and confirmatory factor analysis (CFA) were used to validate the translation. Mixed linear regression models were used to identify factors influencing CARE results, and a multivariable logistic regression analysis was done to determine the predictive value of CARE results on quality of life (QoL). Results A total of 283 patients undergoing prostatectomy (n = 146, 51%), partial/radical nephrectomy (n = 70, 25%) or cystectomy (n = 67, 24%) responded to the survey. Internal consistency was high (α = 0.649–0.920) and the CFA showed a factor loading > 0.5 in 17/27 items. Significant main effects were found for the time of survey and type of surgery, while a time by type interaction was only found for the gastrointestinal subscale ($$\chi_{(4)}^{2}$$ χ ( 4 ) 2 = 30.37, p 0.0001) and the total CARE score (TCS) ($$\chi_{(4)}^{2}$$ χ ( 4 ) 2 = 13.47, p = 0.009) for cystectomy patients, meaning a greater score decrease at discharge and lower level of recovery at follow-up. Complications demonstrated a significant negative effect on the TCS ($$\chi_{(2)}^{2}$$ χ ( 2 ) 2 = 8.61, p = 0.014). A high TCS at discharge was an independent predictor of a high QLQ-C30 QoL score at follow-up (OR = 5.26, 95%-CI 1.42–19.37, p = 0.013). Conclusion This German translation of the CARE can serve as a valid ePROM to measure recovery and predict QoL after major urological surgery.

To develop a new digital biomarker based on the analysis of primary tumour tissue by a convolutional neural network (CNN) to predict lymph node metastasis (LNM) in a cohort matched for already established risk factors.Haematoxylin and eosin (HE) stained primary tumour slides from 218 patients (102 N+; 116 N0), matched for Gleason score, tumour size, venous invasion, perineural invasion and age, who underwent radical prostatectomy were selected to train a CNN and evaluate its ability to predict LN status.With 10 models trained with the same data, a mean area under the receiver operating characteristic curve (AUROC) of 0.68 (95% confidence interval [CI] 0.678-0.682) and a mean balanced accuracy of 61.37% (95% CI 60.05-62.69%) was achieved. The mean sensitivity and specificity was 53.09% (95% CI 49.77-56.41%) and 69.65% (95% CI 68.21-71.1%), respectively. These results were confirmed via cross-validation. The probability score for LNM prediction was significantly higher on image sections from N+ samples (mean [SD] N+ probability score 0.58 [0.17] vs 0.47 [0.15] N0 probability score, P = 0.002). In multivariable analysis, the probability score of the CNN (odds ratio [OR] 1.04 per percentage probability, 95% CI 1.02-1.08; P = 0.04) and lymphovascular invasion (OR 11.73, 95% CI 3.96-35.7; P0.001) proved to be independent predictors for LNM.In our present study, CNN-based image analyses showed promising results as a potential novel low-cost method to extract relevant prognostic information directly from HE histology to predict the LN status of patients with prostate cancer. Our ubiquitously available technique might contribute to an improved LN status prediction.

Scientific evidence in medicine is based on data generated from research. Recently, the number of scientifically active physicians has decreased, which has led to the development of the Clinician Scientist Programs. To better structure and focus the research of young physicians, we aimed to investigate the impact of collaborations and other factors on the quality and output of scientific publications.The abstracts of three annual congresses of the German Society of Urology were systematically analysed regarding content, collaborations, and study design. Full-text publications and journals were identified through a MEDLINE® search. Impact factors (IFs) were identified using Journal Citation Reports™. To identify factors which predict publication and IFs, χ1,074 abstracts were reviewed. The publication rate of subsequent peer-reviewed full-text publications was 52.5%. Collaborations with at least one institution (odds ratio (OR) 2.02, 95% confidence interval (CI) 1.48-2.76, p0.0001), statistical analysis (OR 1.92, 95% CI 1.41-2.60, p0.0001), study design (prospective vs. retrospective: OR 1.43, 95% CI 1.06-1.93, p=0.021), and national collaborations (OR 1.43, 95% CI 1.04-1.98, p=0.029) increased the likelihood of publication in a peer-reviewed journal in a multivariable logistic regression analysis. Experimental design (OR 2.77, 95% CI 1.32-5.84, p=0.007), international collaborations (OR 2.26, 95% CI 1.23-4.15, p=0.009), oncologic topics (OR 1.94, 95% CI 1.23-3.07, p=0.005), prostate disease (OR 1.75, 95% CI 1.08-2.84, p=0.023), and statistical analysis (OR 1.68, 95% CI 1.06-2.64, p=0.026) were associated with a higher IF.Abstracts resulting from collaborative research projects had a higher likelihood of subsequent full-text publication and a higher IF. More full-text publications were reported when abstracts included a statistical analysis. Hence, intensive networking (e. g. at congresses and workshops) of researching physicians as well as statistical/biometrical classes could be key factors to improve academic success.

Since multiple oncological treatment options in metastatic castration-resistant prostate cancer (mCRPC) are available, optimal sequencing of therapies are under investigation. However, the efficacy of Cabazitaxel (CAB) in fourth and later lines of therapy is rarely investigated.Fifty three patients with mCRPC treated with CAB in fourth line or later were included in our retrospective study, which involved eight uro-oncology centers in Germany. Clinical and tumor characteristics, as well as PSA-response rates were analyzed. Kaplan-Meier plots addressed overall survival (OS) and progression-free survival (PFS). Logistic regression models predicted risk factors of overall mortality (OM).Of 53 patients, 79% (n=42), 19% (n=10) and 2% (n=1) received CAB in fourth, fifth and sixth line. A median of 4 cycles of CAB were administered. Median PSA at start of CAB was 199ng/ml (interquartile range (IQR) 70-869). In total, 89% had bone and 40% visceral metastases prior to the start of CAB. Moreover, 30% of patients received Docetaxel in first line therapy for mCRPC. Most frequent sequence of therapy was abiraterone followed by docetaxel and followed by enzalutamide. Overall, median PSA-response rate was -20% (IQR -80 to +10%). Patients with docetaxel in first line had a significantly better median PSA-response on CAB (-80 vs. 20%, P=0.03). Median OS, radiographic PFS and overall PFS were 14.8 (Confidence interval (CI): 11.0-20.8), 3.0 (CI: 2.9-4.0) and 2.9 (CI: 2.0-3.3) months, respectively. In multivariable analyses, visceral metastases, PSA100ng/ml, ISUP4+5 and later administration of Docetaxel were predictors of OM.Real-world experiences indicate that favorable oncologic outcomes can be achieved with CAB especially regarding PSA-response and OS even in the fourth line or later in patients with mCRPC.

To assess the baseline inflammatory markers modified Glasgow Prognostic Score (mGPS), systemic immune-inflammation index (SII), and neutrophile-to-lymphocyte ratio (NLR) as pragmatic tools for predicting response to chemohormonal therapy (docetaxel plus ADT) and prognosis in men with metastatic hormone-sensitive prostate cancer (mHSPC).Male patients who received docetaxel at a tertiary university care center between 2014 and 2019 were screened for completion of 6 cycles. NLR, SII, mGPS, overall survival (OS), three-year survival, and radiologic response were assessed. Complete response (CR), partial response (PR), and stable disease (SD) were analyzed alone and in combination.Thirty-six mHSPC-patients were included. In thirty patients, baseline mGPS was assessed and was either 0 (n=22) or 2 (n=8). In Cochran-Armitage Trend Test, mGPS showed significant association with the combined radiologic endpoint of "CR, PR, or SD" (p=0.01), three-year survival (p=0.02), and OS (p0.01). Next to prostate-specific antigen (PSA) (HR per 100 units 1.16, 95%CI=1.04-1.30, p0.01), NLR (HR=1.31, 95%CI=1.03-1.66, p=0.03), and mGPS (2 vs. 0, HR=6.53, 95%CI=1.6-27.0, p0.01) at baseline showed significant association with OS in univariable cox regression. However, mGPS remained the only independent predictor for OS in multivariable cox regression (p0.01) and for the combined radiologic endpoint of "CR, PR or SD" (p=0.01) in multivariable logistic regression. SII showed no statistical relevance.Baseline mGPS seems to be a pragmatic tool for clinical decision-making in patients with mHSPC in daily routine.

PLOS ONE 17(8), 1-14 (2022). doi:10.1371/journal.pone.0272656, Published by PLOS, San Francisco, California, US

IntroductionRandomised controlled trials comparing robotic-assisted partial nephrectomy (RAPN) and open PN (OPN) are lacking. Therefore, we aim to report the study protocol and a trial update for a randomised controlled feasibility trial comparing RAPN versus OPN for renal neoplasms.Methods and analysisThe ROBOtic assisted versus conventional Open Partial nephrectomy II trial is designed as a single-centre, randomised, open-label, feasibility trial. Participation will be offered to patients with renal neoplasms and deemed feasible for both, OPN and RAPN. We aim to enrol 50 patients within 15 months using a 1:1 allocation ratio. The primary endpoint of the trial is feasibility of recruitment and will be successful if one third of eligible patients agree to participate. Secondary endpoints include perioperative results, health-related quality of life, inflammatory response as well as surgical ergonomics of the operating team. If the primary outcome, feasibility of recruitment, is successful, the secondary results of the trial will be used for planning a confirmative phase III trial.Ethics and disseminationEthical approval was obtained from the local institutional review board (Ethik-Kommission II at Heidelberg University: 2020-542N). Results will be made publicly available in peer-reviewed scientific journals and presented at appropriate congresses and social media.Trial registration numberNCT04534998.

ObjectivesTo explore men´s onset and burden of lower limb lymphedema (LLL) after radical prostatectomy (RP) with pelvic lymph node dissection.Patients and methodsA cross-sectional survey-based study was conducted nation-wide and web-based in Germany. Part 1 included 15 multidisciplinary compiled questions with three questions from Short Form 12 Health Survey (SF-12) and WHO activity recommendation, part 2 the validated German Lymph-ICF-Questionnaire (Lymph-ICF-LL). Subgroup comparisons and simple regression analyses were used to identify factors associated with therapy and burden of LLL, followed by multiple regression analyses to explain variance in impairment in the patients’ daily life.Results54 patients completed the survey. Median time of LLL-onset was reported with 2.0 (0.5-9.75) months after RP. 19 patients (35.2%) reported bilateral lymphedema, 28 (51.9%) the use of individually fitted compression stockings (CS), 25 (46.3%) of manual lymphatic drainage (LD) and 26 (48.1%) complete regression.The Lymph-ICF-LL revealed a higher total burden for patients with an active LLL compared to complete regression (total score: 25.5 vs. 11.9, p=0.01) specially for “physical function” (28.3 vs. 12.9, p=0.004) and “mental function” (26.2 vs. 6.7, pConclusionMen with LLL after RP with PLND report a significant burden in daily life. Bbasic therapy needs to be offered early. Postoperative onset of LLL is variable, which should be considered when assessing complications after RP.

Background Data from interventional studies suggest that a peritoneal flap after pelvic lymph node dissection (LND) during laparoscopic, robotic-assisted radical prostatectomy (RARP) may reduce the rate of symptomatic lymphoceles in transperitoneal approach. However, most of these studies are not conducted in a randomized controlled fashion, thus limiting their scientific value. A recent prospective, randomized, controlled trial (RCT) did not show superiority of a peritoneal flap while further trials are lacking. Therefore, the aim of the presented RCT will be to show that creating a peritoneal flap decreases the rate of symptomatic lymphoceles compared to the current standard procedure without creation of a flap. Methods/design PELYCAN is a parallel-group, patient- and assessor-blinded, phase III, adaptive randomized controlled superiority trial. Men with histologically confirmed prostate cancer who undergo transperitoneal RARP with pelvic LND will be randomly assigned in a 1:1 ratio to two groups—either with creating a peritoneal flap (PELYCAN) or without creating a peritoneal flap (control). Sample size calculation yielded a sample size of 300 with a planned interim analysis after 120 patients, which will be performed by an independent statistician. This provides a possibility for early stopping or sample size recalculation. Patients will be stratified for contributing factors for the development of postoperative lymphoceles. The primary outcome measure will be the rate of symptomatic lymphoceles in both groups within 6 months postoperatively. Patients and assessors will be blinded for the intervention until the end of the follow-up period of 6 months. The surgeon will be informed about the randomization result after performance of vesicourethral anastomosis. Secondary outcome measures include asymptomatic lymphoceles at the time of discharge and within 6 months of follow-up, postoperative complications, mortality, re-admission rate, and quality of life assessed by the EORTC QLQ-C30 questionnaire. Discussion The PELYCAN study is designed to assess whether the application of a peritoneal flap during RARP reduces the rate of symptomatic lymphoceles, as compared with the standard operation technique. In case of superiority of the intervention, this peritoneal flap may be suggested as a new standard of care. Trial registration German Clinical Trials Register DRKS00016794. Registered on 14 May 2019.

Introduction: Screening for and treating asymptomatic bacteriuria (ABU) or administering antibiotic prophylaxis is recommended during ureteral stent and nephrostomy interventions. This study investigates the frequency of postinterventional infectious complications to gain insight into the need for antibiotics. Methods: Between September 2016 and June 2019, 168 insertions/exchanges of ureteral stents or nephrostomies were recorded in a prospective multicenter study. Patients without a symptomatic UTI did not receive antibiotic treatment/prophylaxis. Asymptomatic patients in whom their urologist already administered an antibiotic treatment served as a comparative group. Follow-up included postinterventional complications within 30 days. Symptoms were assessed by the Acute Cystitis Symptom Score (ACSS) before and after the intervention. Predictors of increasing postinterventional symptoms were analyzed by a multivariable logistic regression model. Results: One hundred forty-five interventions were eligible. One hundred twenty-two (84.1%) interventions were performed without antibiotic treatment. Preinterventional ABU was detected in 54.4% and sterile urine in 22.8% (22.8% without culture). Postinterventional infectious complications did not differ between patients with versus without antibiotics. Transurethral interventions aggravate symptoms (p = 0.034) but do not increase infectious complications compared to percutaneous interventions. Patients without diabetes mellitus are at higher risk for increasing symptoms. Conclusion: Results indicate that peri-interventional antibiotic treatment may be omitted in patients without symptomatic UTI. Symptoms must be differentiated between infectious and procedure-associated origins.

Background The cell surface interleukin 22 (IL-22) receptor complex is mainly expressed in epithelial and tissue cells like pancreatitis cells. Recent studies described that IL-22R was overexpressed in malignant diseases and was associated with a poor overall survival (OS). The role of IL-22RA1 gene expression in muscle invasive bladder cancer (MIBC) has not been investigated, yet. Objectives The aim of this study was to analyze the role of IL-22RA1 gene expression in patients with MIBC. Methods In a cohort of 114 patients with MIBC who underwent radical cystectomy, IL-22RA1 gene expression was analyzed with qRT-PCR and correlated with clinical parameters. Furthermore, Kaplan-Meier and Cox regression analysis were performed. For validation, an in silico dataset (TCGA 2017, n=407) was reanalyzed. Results IL-22RA1 gene expression was independent of clinicopathological parameters like age (P=0.2681), T stage (P=0.2130), nodal status (P=0.3238) and lymph vascular invasion (LVI, P=0.5860) in patients with MIBC. A high expression of IL-22RA1 was associated with a shorter OS (P=0.0040) and disease-specific survival (P=0.0385). Furthermore, a shorter disease-free survival (DFS) was also associated with a high expression of IL-22RA1 (P=0.0102). In the multivariable analysis, IL-22RA1 expression was an independent prognostic predictors regarding OS (P=0.0096, HR=0.48). In the TCGA cohort, IL-22RA1 expression was independent regarding to OS and DFS. Conclusion A high IL-22RA1 gene expression was associated with worse outcome. Furthermore, IL-22RA1 represented an independent predictor regarding OS in our cohort and therefore might be used for risk stratification in patients with MIBC.

BACKGROUND/AIM This study investigated the impact of available preoperative imaging on the reliability and predictive accuracy of RENAL and PADUA nephrometry-scoring systems for renal tumors. PATIENTS AND METHODS Five urologists determined RENAL and PADUA scores using preoperative imaging data (computed tomography and magnetic resonance imaging) of 100 patients admitted for partial nephrectomy with the following combinations: T0: transverse planes without excretory phase (EP), TC0: transverse and coronal planes without EP, TC1: transverse and coronal planes with EP. Reference standard was obtained by a uro-radiologist. Ischemia time was used as surrogate for surgical complexity. RESULTS Assignment of EP significantly reduced interobserver-variability among urologists (p

AIM To analyze the safety and efficiency of direct-acting antiviral (DAA) regimens in liver-transplanted patients with hepatitis C virus (HCV) reinfection. METHODS Between January 2014 and December 2016, 39 patients with HCV reinfection after liver transplantation were treated at our tertiary referral center with sofosbuvir (SOF)-based regimens, including various combinations with interferon (IFN), daclatasvir (DAC), simeprivir (SIM) and/or ledipasvir (LDV). Thirteen patients were treated with SOF + IFN ± RBV. Ten patients were treated with SOF + DAC ± RBV. Fiveteen patients were treated with fixed-dose combination of SOF + LDV ± RBV. One patient was treated with SOF + SIM + RBV. Three patients with relapse were retreated with SOF + LDV + RBV. The treatment duration was 12-24 wk in all cases. The decision about the HCV treatment was made by specialists at our transplant center, according to current available or recommended medications. RESULTS The majority of patients were IFN-experienced (29/39, 74.4%) and had a history of hepatocellular carcinoma (26/39, 66.7%) before liver transplantation. Sustained virological response at 12 wk (SVR12) was achieved in 10/13 (76.9%) of patients treated with SOF + IFN ± RBV. All patients with relapse were treated with fixed-dose combination of SOF + LDV + RBV. Patients treated with SOF + DAC + RBV or SOF + LDV + RBV achieved 100% SVR12. SVR rates after combination treatment with inhibitors of the HCV nonstructural protein (NS)5A and NS5B for 24 wk were significantly higher, as compared to all other therapy regimens (P = 0.007). Liver function was stable or even improved in the majority of patients during treatment. All antiviral therapies were safe and well-tolerated, without need of discontinuation of treatment or dose adjustment of immunosuppression. No serious adverse events or any harm to the liver graft became overt. No patient experienced acute cellular rejection during the study period. CONCLUSION Our cohort of liver-transplanted patients achieved high rates of SVR12 after a 24-wk course of treatment, especially with combination of NS5A and NS5B inhibitors.