Urinary microbiome differences between lichen sclerosus induced and non-lichen sclerosus induced urethral stricture disease.

OBJECTIVE: To describe differences in the urinary microbiome of patients with pathologically confirmed lichen sclerosus (LS) urethral stricture disease (USD) vs non-lichen sclerosus (non-LS) USD pre- and post-operatively. METHODS: Patients were pre-operatively identified and prospectively followed, all underwent surgical repair and had tissue samples obtained to make a pathological diagnosis of LS. Pre- and post-operative urine samples were collected. Bacterial genomic DNA was extracted. Alpha and beta diversity measurements were calculated and compared. A zero-inflated negative binomial model was utilized to compare taxa abundances between disease status and surgery status. RESULTS: Urine samples were obtained from both cohorts, 69 samples in total: 36 samples were obtained pre-operatively and 33 samples were obtained post-operatively. Ten patients provided both a pre-operative and post-operative urine sample. Twenty-six patients had pathological evidence of LS and 33 patients did not. There was a statistically significant difference in alpha diversity between the pre-operative urine samples of patients with non-LS USD and LS USD, (p = 0.01). There was no significant difference in alpha diversity within post-operative urine samples between patients with non-LS USD and LS USD, (p = 0.1). A significant difference was observed in Weighed UniFrac distances with respect to disease and operative status, (p = 0.001 and 0.002). CONCLUSIONS: LS USD have significant alterations in diversity and differential abundance of urine microbiota compared to non-LS USD controls. These findings could be used to guide further investigations into the role of the urinary microbiome in LS USD pathogenesis, severity of presentation, and stricture recurrence.

A novel prognostic model predicting overall survival in patients with metastatic castration-resistant prostate cancer receiving standard chemotherapy: A multi-trial cohort analysis.

PURPOSE: Generalizable, updated, and easy-to-use prognostic models for patients with metastatic castration-resistant prostate cancer (mCRPC) are lacking. We developed a nomogram predicting the overall survival (OS) of mCRPC patients receiving standard chemotherapy using data from five randomized clinical trials (RCTs). METHODS: Patients enrolled in the control arm of five RCTs (ASCENT 2, VENICE, CELGENE/MAINSAIL, ENTHUSE 14, and ENTHUSE 33) were randomly split between training (n = 1636, 70%) and validation cohorts (n = 700, 30%). In the training cohort, Cox regression tested the prognostic significance of all available variables as a predictor of OS. Independent predictors of OS on multivariable analysis were used to construct a novel multivariable model (nomogram). The accuracy of this model was tested in the validation cohort using time-dependent area under the curve (tAUC) and calibration curves. RESULTS: Most of the patients were aged 65-74 years (44.5%) and the median (interquartile range) follow-up time was 13.9 (8.9-20.2) months. At multivariable analysis, the following were independent predictors of OS in mCRPC patients: sites of metastasis (visceral vs. bone metastasis, hazard ratio [HR]: 1.24), prostate-specific antigen (HR: 1.00), aspartate transaminase (HR: 1.01), alkaline phosphatase (HR: 1.00), body mass index (HR: 0.97), and hemoglobin (≥13 g/dl vs. <11 g/dl, HR: 0.41; all p < 0.05). A nomogram based on these variables was developed and showed favorable discrimination (tAUC at 12 and 24 months: 73% and 72%, respectively) and calibration characteristics on external validation. CONCLUSION: A new prognostic model to predict OS of patients with mCRPC undergoing first line chemotherapy was developed. This can help urologists/oncologists in counseling patients and might be useful to better stratify patients for future clinical trials.

Outcomes of Surgery in Peyronie's Disease Following Intralesional Collagenase Clostridium Histolyticum Injections.

PURPOSE OF REVIEW: To explore the potential hurdles surgeons may encounter when preforming surgical correction of penile curvature in patients with Peyronie's Disease following intralesional collagenase clostridium histolyticum injections. RECENT FINDINGS: Although limited data exists, retrospective analysis of surgeon experiences in surgical treatment of refractory penile curvature in patients with Peyronie's disease appears to not result in more post-operative complications and may only slightly increase intra-operative difficulty. As the use of intralesional collagenase clostridium histolyticum continues to increase and patients who demonstrate persistent curvature despite treatment seek further management, the role of investigating the feasibility of surgery demonstrates significant importance. Although limited data exists, it appears that surgery following intralesional collagenase clostridium histolyticum is safe without added post-operative complications. At the present time, however, further data on intra-operative findings and post-operative outcomes remain necessary, and as the use of this intralesional therapy continues to rise, further information should become readily available.

Outcomes of Urethroplasty for Synchronous Anterior Urethral Stricture Utilizing the Trauma and Urologic Reconstruction Network of Surgeons Length, Segment and Etiology Anterior Urethral Stricture Classification System.

OBJECTIVE: To describe the characteristics, management, and functional outcomes of patients with synchronous urethral stricture disease (SUSD) utilizing a multi-institutional cohort. METHODS: Data were collected and assessed from a prospectively maintained, multi-institutional database. Patients who underwent anterior urethroplasty for urethral stricture disease (USD) were included and stratified by the presence or absence of SUSD. USD location and etiology were classified according to the Trauma and Urologic Reconstruction Network of Surgeons Length, Segment and Etiology Anterior Urethral Stricture Classification System. Anterior urethroplasty techniques were recorded for both strictures. Functional failure was compared between groups. RESULTS: One thousand nine hundred eighty-three patients were identified, of whom, 137/1983 (6.9%) had SUSD. The mean primary stricture length for patients with SUSD was 3.5 and 2.6 cm for the secondary stricture. Twelve anterior urethroplasty technique combinations were utilized in treating the 27 different combinations of SUSD. Functional failure was noted in 18/137 (13.1%) patients with SUSD vs 192/1846 (10.4%) patients with solitary USD, P = .3. SUSD was not associated with increased odds of functional failure. S classifications: S1b, P = .003, S2a, P = .001, S2b, P = .01 and S2c, P = .02 and E classifications: E3a, P = .004 and E6, P = .03, were associated with increased odds of functional failure. CONCLUSION: Repair of SUSD in a single setting does not increase the risk of functional failure compared to patients with solitary USD. Increasing S classification, S1b through S2c and E classifications E3a and E6 were associated with increased functional failure. This reinforces the importance of the Trauma and Urologic Reconstruction Network of Surgeons Length, Segment and Etiology Anterior Urethral Stricture Classification System as a necessary tool in large-scale multi-institutional analysis when assessing highly heterogenous patient populations.

Urinary catheter alleviation navigator protocol (UCANP): Overview of protocol and review of initial experience.

BACKGROUND: Given the associated morbidity, mortality, and financial consequences of catheter associated urinary tract infections (CAUTIs), efforts should be made to mitigate the risk. We sought to describe, and report results for a post-catheter removal bladder management protocol focused on decreasing catheter reinsertion, catheter days, and overall CAUTI risk. METHODS: This was a quality improvement initiative implemented over a 3-month period at a single urban, tertiary health care center. Patients with an indwelling urinary catheter deemed eligible for removal were followed and cared for according to the study protocol. Rates of catheter reinsertion, catheter days, and assessment of CAUTI risk were compared between cohorts. RESULTS: A total of 173 patients were eligible for protocol enrollment. Catheter reinsertion rate was 16% during the pilot, compared to 21% and 27% for the historical cohorts, (P = .02). The mean number of catheter day's during the study was 1.4 days, compared to 9.5 and 5.6 days in the historical cohorts (P = .004). Catheter hours (OR 1.010 95% CI 1.005 - 1.015 P < .0001.) was a predictor of catheter reinsertion during the pilot. CONCLUSIONS: Our protocol resulted in a reduction of catheter reinsertion rates and number of catheter days. Expansion of this protocol to a larger patient cohort is required.

Robotic vs Laparoscopic Nephroureterectomy for Upper Tract Urothelial Carcinoma: A Multicenter Propensity-Score Matched Pair "tetrafecta" Analysis (ROBUUST Collaborative Group).

Purpose: To compare the outcomes of robotic radical nephroureterectomy (RRNU) and laparoscopic radical nephroureterectomy (LRNU) within a large multi-institutional worldwide dataset. Materials and Methods: The ROBotic surgery for Upper tract Urothelial cancer STudy (ROBUUST) includes data from 17 centers worldwide regarding 877 RRNU and LRNU performed between 2015 and 2019. Baseline features, perioperative and oncologic outcomes, were included. A 2:1 nearest-neighbor propensity-score matching with a 0.001 caliper was performed. A univariable and a multivariable logistic regression model were built to evaluate the predictors of a composite "tetrafecta" outcome defined as occurrence of bladder cuff excision+LND+no complications+negative surgical margins. Results: After matching, 185 RRNU and 91 LRNU were assessed. Patients in the RRNU group were more likely to undergo bladder cuff excision (81.9% vs 63.7%; p < 0.001) compared to the LRNU group. A statistically significant difference was found in terms of overall postoperative complications (p = 0.003) and length of stay (p < 0.001) in favor of RRNU. Multivariable analysis demonstrated that LRNU was an independent predictor negatively associated with achievement of "tetrafecta" (odds ratio: 0.09; p = 0.003). Conclusions: In general, RRNU and LRNU offer comparable outcomes. While the rate of overall complications is higher for LRNU in this study population, this is mostly related to low-grade complications, and therefore with more limited clinical relevance. RRNU seems to offer shorter hospital stay, but this might also be related to the different geographical location of participating centers. Overall, the implementation of robotics might facilitate achievement of a "tetrafecta" outcome as defined in the present study.

Long-term Risk of Recurrence in Surgically Treated Renal Cell Carcinoma: A Post Hoc Analysis of the Eastern Cooperative Oncology Group-American College of Radiology Imaging Network E2805 Trial Cohort.

Currently, surveillance guidelines following surgical resection of clinically localized renal cell carcinoma (RCC) are clear within the first 5 yr; however, these lack the same degree of objectivity following this cutoff. We sought to investigate the long-term risk of recurrence in surgically treated RCC in order to determine the utility of long-term surveillance. A post hoc analysis of patients within the Eastern Cooperative Oncology Group-American College of Radiology Imaging Network (ECOG-ACRIN) E2805 trial cohort was performed. The 36-mo cumulative incidence of recurrence was assessed at set intervals following surgery, in order to dynamically assess recurrence through the use of a conditional survival model. Of the 1943 patients included in the original cohort, 730 developed recurrence. The 36-mo cumulative incidences of recurrence were found to be 31%, 26%, 19%, 16%, 19%, and 20% for patients at 0, 12, 24, 36, 48, and 60 mo from surgery, respectively. At 0 mo from surgery, age, pathological T3/4 stage (hazard ratio [HR] = 1.56), pathological N1/2 stage (HR = 2.38), and Fuhrman grades 3 and 4 (HR = 1.36 and HR = 2.41, respectively) were independent predictors of recurrence; however, this was not seen at 60 mo following surgery. These findings support that surveillance imaging should be performed beyond 5 yr following surgical resection of intermediate- to high-risk RCC. PATIENT SUMMARY: : Follow-up for surgically resected localized renal cell carcinoma should be performed beyond 5 yr, for the rates of recurrence remain significant beyond this 5 yr endpoint.

Combination of pembrolizumab and BCG treatment after endoscopic ablation of high-risk superficial upper urinary tract urothelial carcinoma in patients not candidates for radical nephroureterectomy: protocol for phase-II study.

INTRODUCTION: The treatment standard for high-risk upper urinary tract urothelial carcinoma (UUTUC) is radical nephroureterectomy. However, some patients may be unfit or unwilling, and in such patients the available alternatives are suboptimal. Therapies targeting the programmed death (PD) pathway have shown promise in urothelial carcinom (UC). We designed the current study to determine the safety and efficacy of administering MK-3475 (a monoclonal antibody targeting interaction between PD-1 and its ligand) in combination with bacillus Calmette-Guerin (BCG) in high-risk non-muscle invasive UUTUC patients. METHODS: This represents a single-centre phase-II efficacy study of MK-3475 therapy in combination with BCG for subjects, 18 years of age or older, with pathologically documented non-muscle invasive high-risk UUTUC unfit or unwilling to be treated with radical nephroureterectomy. Twenty subjects will be enrolled; patients will receive treatment with 200 mg of MK-3475 every 21 days, starting 2 weeks from the initial endoscopic resection and continuing for 6 weeks after the final dose of BCG. The primary objective is to determine the safety and efficacy of administering MK-3475 at a fixed dose of 200 mg every 3 weeks in conjunction with intrapelvic BCG. Secondary objectives include 19 week and the 3, 12 and 24-month post-treatment completion complete response and progression-free rate assessments. ETHICS AND DISSEMINATION: The study has been approved by the Institutional Review Board of the Henry Ford Hospital. The results of this study will be published in a peer-reviewed journal and presented at a scientific conference. TRIAL REGISTRATION NUMBER: NCT03345134.

Protocol for phase I study of pembrolizumab in combination with Bacillus Calmette-Guérin for patients with high-risk non-muscle invasive bladder cancer.

INTRODUCTION: The initial treatment for high-risk non-muscle invasive bladder cancer (NMIBC) is endoscopic resection of the tumour followed by BCG therapy. In those who develop recurrence, the standard treatment is radical cystectomy. Despite the advancement in surgical technique and postoperative care, the degree of morbidity associated with radical cystectomy remains high, therefore less invasive treatment modalities are desirable. Therapies targeting the programmed death (PD) pathway have shown promise in urothelial carcinoma. We undertook the current study to determine the safety and efficacy of administering pembrolizumab (a monoclonal antibody targeting the interaction between PD-1 and its ligand) in combination with BCG in high-risk NMIBC. METHODS: This is a single-centre phase I safety and efficacy study of pembrolizumab used in combination with intravesicular BCG treatment for subjects with pathologically documented high-risk NMIBC despite having received two courses of induction therapy or BCG treatment followed by maintenance BCG. Fifteen subjects will be enrolled, patients will receive treatment with 200 mg of pembrolizumab every 21 days, starting 2 weeks from the initial endoscopic resection and continuing for 6 weeks after the final dose of BCG. The primary objective is to determine the safety of administering pembrolizumab at a fixed dose of 200 mg every 3 weeks in conjunction with intravesicular BCG treatment in patients with high-risk NMIBC who have failed previous treatment. Secondary objectives are to determine the 19 weeks and the 3, 12 and 24 months post-treatment completion complete response rate with combined pembrolizumab and intravesicular BCG therapy in the aforementioned patients. ETHICS AND DISSEMINATION: The study has been approved by the Institutional Review Board of the Henry Ford Hospital. The results of this study will be published in a peer-reviewed journal and presented at a scientific conference. TRIAL REGISTRATION NUMBER: NCT02324582.