Quality-of-life outcomes of the ROBOtic-assisted versus Conventional Open Partial nephrectomy (ROBOCOP) II trial.

OBJECTIVES: To comprehensively compare quality-of-life (QoL) outcomes between open partial nephrectomy (OPN) and robot-assisted PN (RAPN) from the randomised ROBOtic-assisted versus Conventional Open Partial nephrectomy (ROBOCOP) II trial, as QoL data comparing OPN and RAPN are virtually non-existent, especially not from randomised controlled trials (RCTs). PATIENTS AND METHODS: The ROBOCOP II was a single-centre, open-label RCT between OPN and RAPN. The pre-planned analyses of QoL outcomes are presented. Data were analysed descriptively in a modified intention-to-treat population. RESULTS: A total of 50 patients underwent surgery. At postoperative Day 90 (POD90), there was no significant difference for the Kidney Disease Quality of Life-Short Form questionnaire score (mean [sd] OPN 72 [20] vs RAPN 76 [15], P = 0.850), while there were advantages for RAPN in the subdomains of 'Pain' (P = 0.006) and 'Physical functioning' (P = 0.011) immediately after surgery. For the European Organisation for Research and Treatment of Cancer quality of life questionnaire 30-item core there were overall advantages directly after surgery (mean [sd] score OPN 63 [20] vs RAPN 75 [17], P = 0.031), as well as for the subdomains 'Fatigue' (P = 0.026), 'Pain' (P = 0.002) and 'Constipation' (P = 0.045) but no differences at POD90. There were no differences for the EuroQoL five Dimensions five Levels questionnaire at POD90 (mean [sd] score OPN 70 [22] vs RAPN 72 [17], P = 1.0) or at any other time point. Finally, no significant differences were found for the overall Convalescence and Recovery Evaluation questionnaire score at POD90 (mean [sd] OPN 84 [13] vs RAPN 86 [10], P = 0.818) but less pain in the RAPN group (P = 0.017) directly after surgery. CONCLUSIONS: Pain and physical functioning as subdomains of QoL are improved after RAPN compared to OPN in the early postoperative course, while there are no differences anymore after 3 months.

[Incidence, therapy, and prognosis of prostate cancer in Baden-Württemberg: analysis based on cancer registry data]. / Inzidenz, Behandlung und Prognose des Prostatakarzinoms in Baden-Württemberg: Analyse anhand von Krebsregisterdaten.

BACKGROUND: Prostate cancer (PCa) is the most common solid tumor in men in Germany. Collection of epidemiological and clinical data has been centralized for several years due to legal requirements via the state cancer registries. Thus, the reporting of diagnosis, therapy, and progression of cancer is obligatory in Germany. These data needs to be processed based on the questions of the treating physicians. OBJECTIVES: Intention of this work was to present the development of new cases, disease stages, treatment procedures and prognosis of PCa in Baden-Württemberg (BW). METHODS: For this purpose, data of the cancer registry BW regarding patients with PCa first diagnosed between 2013 and 2021 were evaluated. The evaluation was performed using descriptive statistics, Χ2 test and Kaplan-Meier analysis. RESULTS: A total of 84,347 new diagnoses of PCa were reported. Clinical stage was present in 55.3% of patients. Assignment by International Society of Urological Pathology (ISUP) groups was present in 75.7%. A steady increase in primary diagnosis was evident through 2019. The proportion of primary metastatic disease decreased (2013: 19.6% vs. 2021: 12.0%), and the proportion of localized tumors increased (2013: 65.5% vs. 2021: 77.1%). Radical prostatectomy (RP) dominated the treatment of localized tumors with a mean of 60.1%. The proportion of robot-assisted surgery increased from 23.7% (2013) to 60.8% (2021) with a decrease in the R1 rate from 34.8 to 26.2%. Progression-free survival correlated closely with tumor stage and ISUP group. CONCLUSION: An increase in PCa cases and a decrease of advanced tumors were observed. Treatment was mostly surgical in localized stages, with increasing proportion of robotic-assisted RP. Early diagnosis and treatment are critical for long-term prognosis.

Cyclin A2 Expression as Predictive Biomarker in Muscle-Invasive Upper Tract Urothelial Carcinoma.

INTRODUCTION: The aim was to evaluate the prognostic value of altered Cyclin A2 (CCNA2) gene expression in upper tract urothelial carcinoma (UTUC) and to assess its predictive potential as a prognostic factor for overall survival (OS) and disease-free survival. METHODS: 62 patients who underwent surgical treatment for UTUC were included. Gene expression of CCNA2, MKI67, and p53 was analyzed by quantitative reverse transcriptase polymerase chain reaction. Survival analyses were performed using the Kaplan-Meier method and the log-rank test. For Cox regression analyses, uni- and multivariable hazard ratios were calculated. Spearman correlation was used to analyze correlation of CCNA2 expression with MKI67 and p53. RESULTS: The median age of the cohort was 73 years, and it consisted of 48 males (77.4%) and 14 females (22.6%). Patients with high CCNA2 expression levels showed longer OS (HR 0.33; 95% CI: 0.15-0.74; p = 0.0073). Multivariable Cox regression analyses identified CCNA2 overexpression (HR 0.37; 95% CI: 0.16-0.85; p = 0.0189) and grading G2 (vs. G3) (HR 0.39; 95% CI: 0.17-0.87; p = 0.0168) to be independent predictors for longer OS. CCNA2 expression correlated positively with MKI67 expression (Rho = 0.4376, p = 0.0005). CONCLUSION: Low CCNA2 expression is significantly associated with worse OS. Thus, CCNA2 might serve as a potential biomarker in muscle-invasive UTUC and may be used to characterize a subset of patients having an unfavorable outcome and for future risk assessment scores.

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.

Randomized Controlled Feasibility Trial of Robot-assisted Versus Conventional Open Partial Nephrectomy: The ROBOCOP II Study.

BACKGROUND: There is no evidence from randomized controlled trials (RCTs) comparing robot-assisted partial nephrectomy (RAPN) and open partial nephrectomy (OPN). OBJECTIVE: To assess the feasibility of trial recruitment and to compare surgical outcomes between RAPN and OPN. DESIGN, SETTING, AND PARTICIPANTS: ROBOCOP II was designed as single-center, open-label, feasibility RCT. Patients with suspected localized renal cell carcinoma referred for PN were randomized at a 1:1 ratio to either RAPN or OPN. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary outcome was the feasibility of recruitment, assessed as the accrual rate. Secondary outcomes included perioperative and postoperative data. Data were analyzed descriptively in a modified intention-to-treat population consisting of randomized patients who underwent surgery. RESULTS AND LIMITATIONS: A total of 50 patients underwent RAPN or OPN (accrual rate 65%). In comparison to OPN, RAPN had lower blood loss (OPN 361 ml, standard deviation [SD] 238; RAPN 149 ml, SD 122; difference 212 ml, 95% confidence interval [CI] 105-320; p < 0.001), less need for opioids (OPN 46%; RAPN 16%; difference 30%, 95% CI 5-54; p = 0.024), and fewer complications according to the mean Comprehensive Complication Index (OPN 14, SD 16; RAPN 5, SD 15; difference 9, 95% CI 0-18; p = 0.008). OPN has a shorter operative time (OPN 112 min, SD 29; RAPN 130 min, SD 32; difference -18 min, 95% CI -35 to -1; p = 0.046) and warm ischemia time (OPN 8.7 min, SD 7.1; RAPN 15.4 min, SD 7.0; difference 6.7 min, 95% CI -10.7 to -2.7; p = 0.001). There were no differences between RAPN and OPN regarding postoperative kidney function. CONCLUSIONS: This first RCT comparing OPN and RAPN met the primary outcome of the feasibility of recruitment; however, the window for future RCTs is closing. Each approach has advantages over the other, and both remain safe and effective options. PATIENT SUMMARY: For patients with a kidney tumor, open surgery and robot-assisted keyhole surgery are both feasible and safe approaches for partial removal of the affected kidney. Each approach has known advantages. Long-term follow-up will explore differences in quality of life and cancer control outcomes.

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.

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.

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.

Robot-assisted Versus Conventional Laparoscopic Radical Prostatectomy: A Systematic Review and Meta-analysis of Randomised Controlled Trials.

CONTEXT: Robot-assisted radical prostatectomy (RARP) has largely replaced conventional laparoscopic radical prostatectomy (LRP) even though the costs are significantly higher. Justification for this change is the hope for better postoperative functional results because of better dissection of the neurovascular bundle. OBJECTIVE: To perform a systematic review and meta-analysis of randomised controlled trials (RCTs) comparing RARP and LRP for the primary outcome of continence (use of 0 pads or 1 safety pad) at 12 mo after surgery. EVIDENCE ACQUISITION: We searched the CENTRAL, MEDLINE, and Web of Science databases for RCTs comparing RARP versus LRP for adults with localised prostate cancer (PC). Where possible, individual-patient data were obtained. Secondary outcomes were potency for patients potent at baseline; a trifecta of patients continent and potent and no recurrence/further treatment; positive surgical margins; biochemical recurrence; and further treatment for PC. The systematic review was registered prospectively (reviewregistry1190 on www.researchregistry.com/). EVIDENCE SYNTHESIS: Five RCTs were identified. Three trial teams provided data. For another trial, only published data were available. The fifth trial was terminated prematurely because of insufficient recruitment and thus could not be included. Overall, data for 1205 randomised patients were available. At 12 mo, there was no significant difference between the two groups regarding continence (odds ratio [OR] 1.95, 95% confidence interval [CI] 0.67-5.62). However, at 3 mo and 6 mo there were significant differences in favour of RARP. Significantly more patients who were potent at baseline and underwent a robot-assisted nerve-sparing approach were potent at 12 mo (OR 4.05, 95% CI 1.63-10.09). CONCLUSION: At 12 mo after surgery there are no differences in continence between RARP and LRP. Short-term continence benefits of RARP were observed. Potent patients undergoing RARP consistently show better potency postoperatively. PATIENT SUMMARY: We analysed differences between robot-assisted removal of the prostate and conventional keyhole surgery for removal of the prostate. At 12 mo after surgery, there were no differences in continence outcomes between the two approaches. However, patients who were potent at baseline and underwent robot-assisted surgery were more likely to be potent at 12 mo.

Perioperative Outcome of Thulium Laser Enucleation of the Prostate versus Robot-Assisted Simple Prostatectomy: A Propensity Score-Matched Analysis.

INTRODUCTION: The aim of this study was to investigate and compare clinical safety and efficiency of Thulium laser enucleation of the prostate (ThuLEP) and robot-assisted simple prostatectomy (RASP) for the treatment of large gland benign prostatic hyperplasia in a tertiary care center. METHODS: Perioperative data of 39 patients who underwent RASP in our institution from 2015 to 2021 was collected. Propensity score matching using prostate volume, patient age, and body mass index (BMI) was performed from a database of 1,100 Patients treated by ThuLEP from 2009 to 2021. A total of 76 patients were matched. Preoperative parameters such as BMI, age, and prostate volume, as well as intra- and postoperative parameters such as operation time, resection weight, transfusion rate, postoperative catheterization time, length of hospital stay (LoS), hemoglobin drop, postoperative urinary retention (PUR), Clavien-Dindo Classification (CDC), and the Combined Complication Index (CCI), were evaluated. RESULTS: There was no difference in mean hemoglobin drop (2.2 vs. 1.9 g/dL, p = 0.34), yet endoscopic surgery showed superiority in mean operation time (109 vs. 154 min, p < 0.001), mean postoperative catheterization time (3.3 vs. 7.2 days, p < 0.001), and mean LOS (5.4 vs. 8.4 days, p < 0.001). Complication rates evaluated by CDC (p = 0.11) and CCI (p = 0.89) were similar in both groups. Within the documented complications, transfusion rate (0 vs. 3, p = 0.08) and the occurrence of PUR (1 vs. 2, p = 0.5) showed no significant difference. CONCLUSION: ThuLEP and RASP show similar perioperative efficacy and a low rate of complications. ThuLEP had shorter operation times, shorter catheterization time, and a shorter LoS.

A Matched-pair Analysis Comparing Systematic Prostate Biopsy by Conventional Transrectal Ultrasound-guidance Versus Software-based Predefined 3D-Guidance.

OBJECTIVE: To compare software-based three-dimensional-guided systematic prostate biopsy (3D-GSB) with conventional transrectal ultrasound-guided systematic biopsy (TGSB) regarding prostate cancer (PCa) detection rates (CDR). METHODS: In total, 956 patients (200 TGSB patients and 756 3D-GSB patients) without prior positive biopsies and with a prostate-specific antigen value ≤20 ng/ml were eligible for analysis. TGSB and 3D-GSB cases were matched in a 1:1 ratio using propensity score matching with age, prostate-specific antigen, prostate volume, previous biopsy status, and suspicious palpatory finding as confounders. 3D-GSB was conducted with the semi-robotic prostate fusion-biopsy system Artemis. For each patient in both groups, SB was conducted in a similar pattern with 12 cores. All cores in 3D-GSB were automatically planned and mapped on a 3D-model as well as on the real-time transrectal ultrasound imaging. Primary end points were the clinically significant (cs) and overall CDR. Secondary end point was the cancer-positive core rate. RESULTS: After matching, the csCDR was not significantly different between the 3D-GSB and the TGSB groups (33.3% vs 28.8%, P = .385). Overall CDR was significantly higher for 3D-GSB compared to TGSB (55.6% vs 39.9%, P = .002). 3D-GSB detected significantly more non-significant PCa than TGSB (22.2% vs 11.1%, P = .004). In patients with PCa, the number of cancer-positive SB cores was significantly higher by TGSB (42% vs 25%, P < .001). CONCLUSION: 3D-GSB was associated with a higher CDR than TGSB. However, no significant difference was shown in detection of csPCa between both techniques. Therefore, currently, 3D-GSB does not appear to add value to conventional TGSB.

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.

Predicting Complexity in Transurethral Resection of Bladder Tumours: External Validation and Modification of the Bladder Complexity Score.

INTRODUCTION: First external validation of the Bladder Complexity Score (BCS) for predicting complex transurethral resection of bladder tumours (TURBT). METHODS: For BCS calculation, TURBTs performed at our institution between January 2018 and December 2019 were reviewed for the presence of preoperative characteristics listed in the Bladder Complexity Checklist (BCC). Receiver operating characteristics (ROC) analysis was used for BCS validation. To establish a modified BCS (mBCS) with maximum area under the curve (AUC), multivariable logistic regression (MLR) analysis was performed with all BCC-characteristics for different definitions of complex TURBT. RESULTS: 723 TURBTs were included in statistical analyses. Cohort's mean BCS was 11.2 ± 2.4 points (range: 5.5-22 points). In ROC analysis, BCS could not predict complex TURBT (AUC 0.573 [95% CI: 0.517-0.628]). MLR identified tumour size (OR 2.662, p < 0.001), and tumour number > 10 (OR 6.390, p = 0.032) as sole predictors for the modified endpoint of complex TURBT defined as a procedure meeting > 1 criterion: incomplete resection, surgery > 1 h, intraoperative complication, postoperative complications Clavien-Dindo ≥ III. mBCS increased the prediction to an AUC of 0.770 (95% CI: 0.667-0.874). CONCLUSION: In this first external validation, BCS remained an insufficient predictor of complex TURBT. mBCS requires reduced parameters, is more predictive and easier to apply in clinical practice.

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.

Medium-term Oncological Efficacy and Patient-reported Outcomes After Focal High-intensity Focused Ultrasound: The FOXPRO Trial.

BACKGROUND: Multiparametric magnetic resonance imaging (mpMRI)/transrectal ultrasound (TRUS) fusion-guided high-intensity focused ultrasound (HIFU) is a focal treatment option for MRI-visible localized prostate cancer (PCa). High-quality evidence regarding the clinical efficacy remains limited. OBJECTIVE: To assess medium-term oncological efficacy along with patient-reported outcome measures (PROMs). DESIGN, SETTING, AND PARTICIPANTS: This prospective single-center cohort study was performed from 2014 to 2020. Patients with primary International Society of Urological Pathologists (ISUP) grade group (GG) ≤2 by combined MRI/TRUS fusion and systematic prostate biopsy and prostate-specific antigen (PSA) <10 ng/ml were included. INTERVENTION: MRI/TRUS fusion-guided focal HIFU therapy. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary outcome was the cancer-free rate of the HIFU-treated lesion by biopsy after 1 yr. Secondary endpoints included salvage treatment-free survival (STFS), metastasis-free survival (MFS), overall survival (OS), and PROMs according to International Consortium for Health Outcomes Measurement recommendations. RESULTS AND LIMITATIONS: Fifty patients were included (median [range] age 68 [48-80] yr; median PSA 6.5 [1.2-9.9] ng/ml; GG 1 54% [n = 27], and GG 2 46% [n = 23]). The median (range) PSA decrease from baseline to 12 mo was 51% (35.9-72.7%). In total, 37/50 patients (74%) underwent a 1-yr biopsy. PCa was detected in 23 patients (46%; GG 1 20% [n = 10]; GG >1 26% [n = 13]; infield 40% [n = 20]). At a median follow-up of 42 (13-73) mo, PCa was detected in 30 men (60%). Among all patients, 19 (38%) underwent salvage treatments (median [95% confidence interval] STFS 53 [44.3-61.7] mo). MFS and OS were 100% and 98%, respectively. The Expanded Prostate Cancer Index Composite-26 sexual domain decreased by 20.8 points (p = 0.372). CONCLUSIONS: MRI/TRUS-guided focal HIFU therapy results in complete cancer ablation in only half of the treated patients after 1 yr, with further recurrences at medium-term follow-up. A decline of potency occurs in a subset of patients. PATIENT SUMMARY: Focal image-guided high-intensity focused ultrasound therapy controls cancer in one of two patients. Its impact on urinary continence and erectile function is low.

Perioperative Antibiotic Prophylaxis in Radical Prostatectomy: "Single-Shot" versus Multiday Regimen.

INTRODUCTION: Perioperative antibiotic prophylaxis (AP) is common in radical prostatectomy (RP). Yet there is no standard recommendation in international guidelines due to poor evidence. It is of great importance that these perioperative AP are sufficiently checked and systemically validated. The objective of this study was to determine whether a "single-shot" (single-use) perioperative AP yields equivalent results compared to a multiday prophylaxis in RP regarding postoperative wound infections and urinary tract infections. METHODS: 376 patients treated by RP at the University Medical Centre Mannheim, from 2014 to 2016, were included in this retrospective study. RP was performed either in a robotic-assisted or open manner. One group received an intravenous dose of perioperative AP with either ciprofloxacin or levofloxacin, continued by an oral dose of AP with ciprofloxacin or levofloxacin until catheter removal, while the other group received a single-shot intravenous perioperative AP with either ciprofloxacin or cefuroxime. RESULTS: There was no significant difference regarding the occurrence of postoperative infections between both AP regimes (p = 0.5). Age, body mass index, and ASA classification did not differ significantly between both groups (p > 0.25). Except for surgery time (p < 0.05), perioperative parameters, such as the preoperative presence of germ-free urine culture, length of hospital stay, catheter time, drain lay time, Gleason score, and TNM stadium, did not differ significantly. CONCLUSION: The present study shows that perioperative single-shot AP does not entail any disadvantage compared to the multiday AP in terms of postoperative infections after RP.

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.

Integrin Expression in Localized Prostate Cancer: A TCGA and MSKCC Cohort-based Exploratory In Silico Analysis.

BACKGROUND/AIM: 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. PATIENTS AND METHODS: 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. RESULTS: 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, ITGß2 and ITGα2. In multivariable cox regression, ITGα2, ITGα10, ITGαD, ITGαB2 (TCGA), ITGα11 and ITGß4 (MSKCC) were independent predictors of DFS. CONCLUSION: The utility of ITGs as PC biomarkers was herein shown.

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.

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.