Tranexamic acid reduces perioperative blood transfusions following open radical cystectomy - a propensity-score matched analysis.

PURPOSE: Radical cystectomy is associated with bleeding and high transfusion rates, presenting challenges in patient management. This study investigated the prophylactic use of tranexamic acid during radical cystectomy. METHODS: All consecutive patients treated with radical cystectomy at a tertiary care university center were included from a prospectively maintained database. After an institutional change in the cystectomy protocol patients received 1 g of intravenous bolus of tranexamic acid as prophylaxis. To prevent bias, propensity score matching was applied, accounting for differences in preoperative hemoglobin, neoadjuvant chemotherapy, tumor stage, and surgeon experience. Key outcomes included transfusion rates, complications, and occurrence of venous thromboembolism. RESULTS: In total, 420 patients were included in the analysis, of whom 35 received tranexamic acid. After propensity score matching, 32 patients and 32 controls were matched with regard to clinicopathologic characteristics. Tranexamic acid significantly reduced the number of patients who received transfusions compared to controls (19% [95%-Confidence interval = 8.3; 37.1] vs. 47% [29.8; 64.8]; p = 0.033). Intraoperative and postoperative transfusion rates were lower with tranexamic acid, though not statistically significant (6% [1.5; 23.2] vs. 19% [8.3; 37.1], and 16% [6.3; 33.7] vs. 38% [21.9; 56.1]; p = 0.257 and p = 0.089, respectively). The occurrence of venous thromboembolism did not differ significantly between the groups (9% [2.9; 26.7] vs. 3% [0.4; 20.9]; p = 0.606). CONCLUSION: Prophylactic tranexamic administration, using a simplified preoperative dosing regimen of 1 g as a bolus, significantly lowered the rate of blood transfusion after cystectomy. This exploratory study indicates the potential of tranexamic acid in enhancing outcomes of open radical cystectomy.

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.

Do we need MRI in all biopsy naïve patients? A multicenter cohort analysis.

PURPOSE: The combined approach (CB) of magnetic resonance imaging (MRI)-guided biopsy (TB) and systematic biopsy (SB) is strongly recommended based on numerous studies in biopsy naïve men with suspicion of clinically significant prostate cancer (csPCA). However, the unbalanced accessibility of MRI, challenges related to reimbursement and the scarcity of specialized medical practitioners continue to impede a widespread implementation. Therefore, our objective was to determine a subset of men that could undergo SB without an increased risk of underdiagnosis at reduced expenses. METHODS: A multicenter analysis of 2714 men with confirmed PCA and suspicious MRI who underwent CB were enrolled. Cancer detection rates were compared between the different biopsy routes SB, TB and CB using McNemar paired test. Additionally, Gleason grade up- and down-grading was determined. RESULTS: CB detected more csPCA than TB and SB (p < 0.001), irrespective of MRI findings or biopsy route (transperineal vs. transrectal). Thereby, single biopsy approaches misgraded > 50% of csPCA. TB showed higher diagnostic efficiency, defined as csPCA detection per biopsy core than CB and SB (p < 0.001). For patients with abnormal DRE and PSA levels > 12.5 ng/ml, PSAD > 0.35 ng/ml/cm3, or > 75 years, SB and CB showed similar csPCA detection rates. CONCLUSION: Conducting CB provides the highest level of diagnostic certainty and minimizes the risk of underdiagnosis in almost all biopsy-naive men. However, in patients with suspicious DRE and high PSA levels, PSAD, or advanced age solely using SB leads to similar csPCA detection rates. Thus, a reduced biopsy protocol may be considered for these men in case resources are limited.

Maximizing efficiency and ensuring safety: Exploring the outcomes of 2 consecutive open radical cystectomies by the same team within a single surgical day.

BACKGROUND: The purpose of this study was to evaluate the outcomes of performing 2 consecutive open radical cystectomies (RCs) within 1 day by the same surgical team. PATIENTS AND METHODS: A retrospective analysis was conducted on data from patients who underwent RC at a single tertiary care center from January 2015 to February 2023. Patient characteristics, perioperative outcomes and endpoints were analyzed. Univariable and multivariable logistic regression models were created to predict major complications. RESULTS: A total of 657 patients were included in the final cohort, containing 64 paired RCs (32 RC1 and 32 RC2) and 593 single RCs. Major complications occurred in 24.7% of the entire cohort, with no significant differences between single RC vs. RC1 and RC2. Paired RCs showed significantly shorter operative time (OT; p = 0.001) and length of stay (LOS; p = 0.047) compared to single RCs. There were no significant differences in transfusion rates, 30-day readmission, 30-day mortality, or histopathological results between paired and single RCs. Multivariable analysis identified patient characteristics such as age (OR = 1.67, p = 0.03), sex (OR = 0.45, p = 0.008), BMI (OR = 1.98, p = 0.007), ASA-score (OR = 1.61, p = 0.04), and OT (OR = 1.87, p = 0.008) as independent predictors of major complications. CONCLUSION: Performing 2 consecutive open RCs within 1 day by the same surgical team is a safe approach in experienced hands. This strategy optimizes the utilization of surgical resources and addresses the growing demand for urologic care while maintaining high-quality patient care. Preoperative planning should consider patient-specific factors to minimize risks associated with major complications. MICRO ABSTRACT: This study evaluates the outcomes of performing 2 consecutive open radical cystectomies (RC) in a single day by the same surgical team. Data from 657 patients who underwent RC at a single tertiary medical center proved that this approach is safe, with no significant differences in major complications. Preoperative planning should consider patient-specific factors for efficient utilization of surgical resources.

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.

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.

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.

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.

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.

Prediction of Significant Prostate Cancer in Equivocal Magnetic Resonance Imaging Lesions: A High-volume International Multicenter Study.

BACKGROUND: Decision of performing prostate biopsy in men with Prostate Imaging Reporting and Data System (PI-RADS) 3 findings in prostate magnetic resonance imaging (MRI) is challenging as they have a low but still relevant risk of harboring significant prostate cancer (sPC). OBJECTIVE: To identify clinical predictors of sPC in men with PI-RADS 3 lesions in prostate MRI and to analyze the hypothetical effect of incorporating prostate-specific antigen density (PSAD) into biopsy decision. DESIGN, SETTING, AND PARTICIPANTS: We analyzed a retrospective multinational cohort from ten academic centers comprising 1476 men who underwent a combined prostate biopsy (MRI targeted plus systematic biopsy) between February 2012 and April 2021 due to a PI-RADS 3 lesion in prostate MRI. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary outcome was the detection of sPC (ISUP ≥2) in a combined biopsy. Predictors were identified by a regression analysis. Descriptive statistics were applied to evaluate the hypothetical effect of involving PSAD into biopsy decision. RESULTS AND LIMITATIONS: Of all patients, 273/1476 (18.5%) were diagnosed with sPC. MRI-targeted biopsy diagnosed fewer sPC cases than combined strategy: 183/1476 (12.4%) versus 273/1476 (18.5%), p < 0.01. Age (odds ratio [OR] 1.10 [95% confidence interval {CI}: 1.05-1.15], p < 0.001), prior negative biopsy (OR 0.46 [0.24-0.89], p = 0.022), and PSAD (p < 0.001) were found to be independent predictors of sPC. Applying a PSAD cutoff of 0.15, 817/1398 (58.4%) biopsies would have been avoided at the cost of missing sPC in 91 (6.5%) men. Limitations were the retrospective design, heterogeneity of the study cohort due to the long inclusion period, and no central revision of MRI. CONCLUSIONS: Age, previous biopsy status, and PSAD were found to be independent predictors of sPC in men with equivocal prostate MRI. Implementation of PSAD into biopsy decision can avoid unnecessary biopsies. Clinical parameters such as PSAD need validation in a prospective setting. PATIENT SUMMARY: In this study, we looked for clinical predictors of significant prostate cancer in men with Prostate Imaging Reporting and Data System 3 lesions in prostate magnetic resonance imaging. We identified age, previous biopsy status, and especially prostate-specific antigen density as independent predictors.

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.

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.

[Immunotherapy in urologic oncology : Response and treatment interruptions due to adverse events in a bicentric real-world analysis]. / Immuntherapien in der Uroonkologie : Ansprechen und Therapieunterbrechungen durch Nebenwirkungen in einer bizentrischen Real-world-Analyse.

BACKGROUND: Immune checkpoint inhibitors (ICI) have been approved in uro-oncology for a few years. Real-world experience regarding benefits and risks with novel side effects are rare. MATERIALS AND METHODS: In a retrospective analysis, all patients who received ICI therapy due to metastatic renal cell carcinoma (NCC) or urothelial carcinoma (UCA) were enrolled at two maximum care hospitals in Germany between July 2016 and May 2021. Radiologic response, progression-free survival (PFS), and adverse events leading to treatment interruption were collected. Oncologic response was compared to randomized controlled trials. RESULTS: In all, 1185 ICI cycles were administered to 145 patients (111 men [77%] and 34 women [23%]): 64 (44.1 %) patients with NCC and 81 (55.9%) patients with UCA received ICI therapy. Of 141 patients with radiological follow-up, an objective response was observed in 21.3% (n = 13) of patients with NCC and 20.0% (n = 16) with UCA (median duration of response 14.9 months [3.0-51.3]). Median PFS was 5.3 months in patients with NCC and 4.8 months with UCA. ICI-associated adverse events requiring treatment interruption were observed in 17.2% patients with NCC and 20.9% with UCA. These were most commonly renal (5.5%: nephritis) and gastrointestinal (4.8%: colitis, diarrhea) adverse events. Hospitalization was required for 22 (15.1%) patients. CONCLUSION: This real-world experience may support patient-centered consultation in treatment decision-making. Further studies on prognostic factors are needed. Therapy interruptions are frequent and the spectrum of side effects requires interdisciplinary treatment.

Baseline Modified Glasgow Prognostic Score (mGPS) Predicts Radiologic Response and Overall Survival in Metastatic Hormone-sensitive Prostate Cancer Treated With Docetaxel Chemotherapy.

BACKGROUND/AIM: 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). PATIENTS AND METHODS: 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. RESULTS: 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 (p<0.01). Next to prostate-specific antigen (PSA) (HR per 100 units 1.16, 95%CI=1.04-1.30, p<0.01), 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, p<0.01) at baseline showed significant association with OS in univariable cox regression. However, mGPS remained the only independent predictor for OS in multivariable cox regression (p<0.01) and for the combined radiologic endpoint of "CR, PR or SD" (p=0.01) in multivariable logistic regression. SII showed no statistical relevance. CONCLUSION: Baseline mGPS seems to be a pragmatic tool for clinical decision-making in patients with mHSPC in daily routine.

Robot-Assisted Simple Prostatectomy vs Endoscopic Enucleation of the Prostate: A Systematic Review and Meta-Analysis of Comparative Trials.

Context: Robot-assisted simple prostatectomy (RASP) and endoscopic enucleation of the prostate (EEP) are two minimally invasive alternatives to simple prostatectomy, which is considered the standard treatment in large prostate glands. It remains unclear which of the two is superior in terms of outcome and complications. Objective: To compare perioperative and functional outcomes of RASP vs EEP. Evidence Acquisition: A systematic review and meta-analysis was conducted according to the recommendations of the Cochrane Collaboration and in line with the PRISMA criteria. The database search included clinicaltrials.gov, Medline (via PubMed), CINAHL, and Web of Science and was using the PICO criteria. All comparative trials were considered. Risk of bias was assessed with the revised ROBINS-I tool. Evidence Synthesis: Seven hundred sixty studies were identified, 4 of which were eligible for qualitative and quantitative analysis, reporting on a total of 901 patients with follow-up up to 24 months. Hemoglobin drop (mean difference [MD] confidence interval [CI]: 0.34 g/dL [0.09-0.58]), the rate of blood transfusions (odds ratio [OR] [CI]: 5.01 [1.60-15.61]) catheterization time (MD [CI]: 3.26 days [1.30-5.23]), and length of hospital stay (LoS) (MD [CI]: 1.94 days [1.11-2.76]) were significantly lower in EEP. No significant differences were seen in operating time and enucleation weight. No significant differences were observed in the incidence of postoperative urinary retention, postoperative transient incontinence, and complications graded according to the Clavien-Dindo classification. Functional results were similar, with no significant differences in International Prostate Symptom Score and maximum urinary flow rate at follow-up. Conclusion: Both EEP and RASP offer excellent improvement of symptoms due to prostatic hyperplasia. EEP has lower blood loss, shorter catheterization time, and LoS and should be the first choice if available. RASP remains an attractive alternative for extremely large glands, in concomitant diseases, or whenever EEP is not available. Review Registration Number (PROSPERO): CRD42021226901.

Onset and burden of lower limb lymphedema after radical prostatectomy: a cross-sectional study.

OBJECTIVES: To explore men's onset and burden of lower limb lymphedema (LLL) after radical prostatectomy (RP) with pelvic lymph node dissection (PLND). PATIENTS AND METHODS: A 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 the Short Form 12 Health Survey (SF-12) and the WHO activity recommendation and part 2 included 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. RESULTS: Fifty-four patients completed the survey. Median time of LLL-onset was reported with 2.0 (0.5-9.75) months after RP. Nineteen 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) especially for "physical function" (28.3 vs. 12.9, p < 0.01) and "mental function" (26.2 vs. 6.7, p < 0.01). In multiple linear regression analysis, a higher BMI (ß = 0.28), lower subjective general health (ß = -0.48), and active lymphedema (ß = 0.28) were significant predictors of higher reported impairments in the Lymph-ICF-LL, accounting for 45.4% of variance. CONCLUSION: Men with LLL after RP with PLND report a significant burden in daily life. Basic therapy needs to be offered early. Postoperative onset of LLL is variable, which should be considered when assessing complications after RP.

Value of Radiomics of Perinephric Fat for Prediction of Intraoperative Complexity in Renal Tumor Surgery.

INTRODUCTION: The aim of this study was to assess the value of computed tomography (CT)-based radiomics of perinephric fat (PNF) for prediction of surgical complexity. METHODS: Fifty-six patients who underwent renal tumor surgery were included. Radiomic features were extracted from contrast-enhanced CT. Machine learning models using radiomic features, the Mayo Adhesive Probability (MAP) score, and/or clinical variables (age, sex, and body mass index) were compared for the prediction of adherent PNF (APF), the occurrence of postoperative complications (Clavien-Dindo Classification ≥2), and surgery duration. Discrimination performance was assessed by the area under the receiver operating characteristic curve (AUC). In addition, the root mean square error (RMSE) and R2 (fraction of explained variance) were used as additional evaluation metrics. RESULTS: A single feature logit model containing "Wavelet-LHH-transformed GLCM Correlation" achieved the best discrimination (AUC 0.90, 95% confidence interval [CI]: 0.75-1.00) and lowest error (RMSE 0.32, 95% CI: 0.20-0.42) at prediction of APF. This model was superior to all other models containing all radiomic features, clinical variables, and/or the MAP score. The performance of uninformative benchmark models for prediction of postoperative complications and surgery duration were not improved by machine learning models. CONCLUSION: Radiomic features derived from PNF may provide valuable information for preoperative risk stratification of patients undergoing renal tumor surgery.