Final Results of a Phase I Trial of WST-11 (TOOKAD Soluble) Vascular-targeted Photodynamic Therapy for Upper Tract Urothelial Carcinoma.

PURPOSE: Vascular-targeted photodynamic therapy with the intravascular photosensitizing agent padeliporfin (WST-11/TOOKAD-Soluble) has demonstrated therapeutic efficacy as an ablative treatment for localized cancer with potential adaptation for endoscopic management of upper tract urothelial carcinoma. This Phase I trial (NCT03617003) evaluated the safety of vascular-targeted photodynamic therapy with WST-11 in upper tract urothelial carcinoma. MATERIALS AND METHODS: Nineteen patients underwent up to 2 endoscopic vascular-targeted photodynamic therapy treatments, with follow-up for up to 6 months. Patients who had residual or recurrent upper tract urothelial carcinoma (any grade/size) failing prior endoscopic treatment or unable or unwilling to undergo surgical resection were eligible for inclusion. The primary endpoint was to identify the maximally tolerated dose of laser light fluence. A dose escalation model was employed, with increasing light fluence (100-200 mW/cm) using a modified continual reassessment method. The secondary endpoint was treatment efficacy, defined by absence of visible tumor and negative urine cytology 30 days posttreatment. RESULTS: Fourteen (74%) patients received the maximally tolerated dose of 200 mW/cm, 2 (11%) of whom experienced a dose-limiting toxicity. The initial 30-day treatment response rate was 94% (50% complete, 44% partial). Eight patients underwent a second treatment, with a final observed 68% complete response rate. Leading toxicities were flank pain (79%) and hematuria (84%), which were transient. No ureteral strictures associated with treatment were identified during follow-up. CONCLUSIONS: Vascular-targeted photodynamic therapy with WST-11 has an acceptable safety profile with strong potential as an effective, kidney-sparing endoscopic management option for upper tract urothelial carcinoma. The recently initiated multicenter Phase 3 ENLIGHTED trial (NCT04620239) is expected to provide further evidence on this therapy.

Survival Impact of Variant Histology Diagnosis in Upper Tract Urothelial Carcinoma.

PURPOSE: Little is known regarding the prognostic implications of variant histology in upper tract urothelial carcinoma (UTUC). We sought to evaluate the impact of variant histology UTUC on patient survival outcomes at our institution. MATERIALS AND METHODS: We identified 705 patients who underwent nephroureterectomy for UTUC at our institution between January 1995 and December 2018. We tested the association between variant histology and cancer-specific survival (CSS) and overall survival (OS) using separate multivariable Cox models after adjusting for pathological stage. RESULTS: Forty-seven patients (6.7%) had variant histology, with prevalence increasing over time (p=0.003). Other demographic and surgical characteristics were similar between variant histology and pure urothelial carcinoma groups. While patients with variant histology were more likely to receive neoadjuvant chemotherapy (38% vs 15%, p <0.001), they were also more likely to have a higher pathological T stage (p <0.001). Variant histology was associated with significantly worse CSS (HR: 2.14; 95% CI 1.33, 3.44; p=0.002) and OS (HR: 1.74; 95% CI 1.15, 2.63; p=0.008). After adjusting for pathological T stage, variant histology was not significantly associated with CSS (HR: 1.17; 95% CI 0.72, 1.89; p=0.5) or OS (HR: 1.20; 95% CI 0.79, 1.84; p=0.4). CONCLUSIONS: Variant histology UTUC is associated with advanced stage and poor survival, and could serve as a useful biomarker for high-risk disease when pathological stage is unknown. However, the inferior CSS and OS with variant histology can be explained by the higher tumor stage on nephroureterectomy. Thus, finding variant histology on surgical pathology does not provide additional prognostic information beyond stage.

Partial versus radical nephrectomy in very elderly patients: a propensity score analysis of surgical, functional and oncologic outcomes (RESURGE project).

PURPOSE: To compare the outcomes of PN to those of RN in very elderly patients treated for clinically localized renal tumor. PATIENTS AND METHODS: A purpose-built multi-institutional international database (RESURGE project) was used for this retrospective analysis. Patients over 75 years old and surgically treated for a suspicious of localized renal with either PN or RN were included in this database. Surgical, renal function and oncological outcomes were analyzed. Propensity scores for the predicted probability to receive PN in each patient were estimated by logistic regression models. Cox proportional hazard models were estimated to determine the relative change in hazard associated with PN vs RN on overall mortality (OM), cancer-specific mortality (CSM) and other-cause mortality (OCM). RESULTS: A total of 613 patients who underwent RN were successfully matched with 613 controls who underwent PN. Higher overall complication rate was recorded in the PN group (33% vs 25%; p = 0.01). Median follow-up for the entire cohort was 35 months (interquartile range [IQR] 13-63 months). There was a significant difference between RN and PN in median decline of eGFR (39% vs 17%; p < 0.01). PN was not correlated with OM (HR = 0.71; p = 0.56), OCM (HR = 0.74; p = 0.5), and showed a protective trend for CSM (HR = 0.19; p = 0.05). PN was found to be a protective factor for surgical CKD (HR = 0.28; p < 0.01) and worsening of eGFR in patients with baseline CKD. Retrospective design represents a limitation of this analysis. CONCLUSIONS: Adoption of PN in very elderly patients with localized renal tumor does not compromise oncological outcomes, and it allows better functional preservation at mid-term (3-year) follow-up, relative to RN. Whether this functional benefit translates into a survival benefit remains to be determined.

Developments in Vascular-Targeted Photodynamic Therapy for Urologic Malignancies.

With improved understanding of cancer biology and technical advancements in non-invasive management of urological malignancies, there is renewed interest in photodynamic therapy (PDT) as a means of focal cancer treatment. The application of PDT has also broadened as a result of development of better-tolerated and more effective photosensitizers. Vascular-targeted PDT (VTP) using padeliporfin, which is a water-soluble chlorophyll derivative, allows for tumor-specific cytotoxicity and has demonstrated efficacy in the management of urologic malignancies. Herein, we describe the evolution of photodynamic therapy in urologic oncology and the role of VTP in emerging treatment paradigms.

Adherence to EAU guidelines on penile cancer translates into better outcomes: a multicenter international study.

INTRODUCTION: We aimed to evaluate adherence to the EAU guidelines (GL) on penile cancer (PC) with regard to primary surgical treatment and management of lymph nodes and to estimate the influence of adherence to GL on clinical outcome. MATERIALS AND METHODS: This is a retrospective multicenter study (PEnile Cancer ADherence study, PECAD Study) on PC patients treated at 12 European and American centers between 2010 and 2016. Adherence to the EAU GL on the surgical management of the primary penile tumor and lymphadenectomy was evaluated. Descriptive analyses were performed, and survival curves were estimated. RESULTS: Data on 425 patients were considered for the analysis. The EAU GL on surgical treatment of the primary tumor and lymphadenectomy were respected in 74.8% and 73.7% of cases, respectively. Survival analysis showed that adherence to the GL on primary penile surgery was significantly associated with a good overall survival [adjusted HR 0.40 (95% CI 0.20-0.83, p value = 0.014)]. Also, the adherence to the GL on lymphadenectomy was statistically significantly associated with overall survival [adjusted HR 0.48 (95% CI 0.24-0.96, p value = 0.038)]. Limited follow-up and retrospective design represent limitations of this study. CONCLUSIONS: Our findings suggest that there is a good adherence to the EAU GL on PC. However, this should be further reinforced, endorsed and encouraged as it might translate into better clinical outcomes for PC patients.

Supra-pubic versus urethral catheter after robot-assisted radical prostatectomy: systematic review of current evidence.

PURPOSE: To provide latest evidence on the use of suprapubic catheter (SPC) versus urethral catheter (UC) after robot-assisted laparoscopic radical prostatectomy (RARP). MATERIALS AND METHODS: A systematic revision of literature was performed up to September 2017 using different search engines (Pubmed, Ovid, Scopus) to identified studies comparing the use of SPC versus standard UC after RARP. Identification and selection of the studies were conducted according to the preferred reporting items for systematic reviews and meta-analysis criteria. For continuous outcomes, the weighted mean difference (WMD) was used as a summary measure, whereas the odds ratio (OR) or risk ratio (RR) with 95% confidence interval (CI) was calculated for binary variables. RR was preferred in cases of a high number of events to avoid overestimation. Pooled estimates were calculated using the random-effect model to account for clinical heterogeneity. All statistical analyses were performed using Review manager 5 (Cochrane Collaboration, Oxford, UK). RESULTS: Eight studies were identified and included in this systematic review, namely 3 RCTs, 4 non-randomized prospective studies, and one retrospective study. A total of 966 RARP cases were collected for the cumulative analysis. Among them, 492 patients received standard UC and 474 SPC placement after RARP. UC patients had higher baseline PSA (WMD 0.44 ng/ml; p = 0.02). Visual Analog Scale (VAS) score was found to be significantly lower in patients with SPC at postoperative day 7 (WMD 0.53; 95% CI 0.13-0.93; p = 0.009). Regarding penile pain, a significant difference in favor of the SPC group was found at postoperative day 7 assessment (WMD 1.2; 95% CI 0.82-1.6; p < 0.001). More patients in the SPC group reported "not at all" or "minimal pain" at this time point (OR 0.17, 95% CI 0.06, 0.44; p < 0.001). No significant differences were found in terms of continence recovery rate at 6-12 weeks between the groups (UC 78.7%, 88.2%; RR 0.92, 95% CI 0.84, 1.01; p = 0.09). Similarly, no differences were found in terms of catheter-related issues (p = 0.17). However, UC patients had lower likelihood of overall complications (OR 0.44, 95% CI 0.21-0.89, p = 0.02). CONCLUSIONS: Available evidence suggests that the use of SPC can be a viable option for postoperative urine drainage after RARP, as it can translate into decreased postoperative pain without carrying a significant higher risk of catheter-related complications. Further investigation seems to be warranted, ideally within the framework of a multicentre randomized study with standardized analysis of outcomes.

Effects of vesical and perfusion pressure on perfusate flow, and flow on vesical pressure, in the isolated perfused working pig bladder reveal a potential mechanism for the regulation of detrusor compliance.

AIMS: Although there is evidence that deficits in bladder blood flow negatively impact bladder function, the effects of vesical, and perfusion pressures on bladder perfusion (perfusate flow), and of perfusate flow on vesical pressure, remain poorly understood. The present study used the isolated perfused working pig bladder model to examine the relationships between blood flow, and vesical and perfusion pressures. METHODS: Vesical arteries of pig bladders obtained from a local slaughterhouse were cannulated and perfused with Krebs-Henseleit solution at different pressures, and with carbachol to cause bladder contraction. The urethra of each bladder was cannulated to permit filling (10 mL/min), isovolumetric contraction and emptying. A ureter was cannulated with a pressure sensor to monitor vesical pressure. RESULTS: When at rest (50 mL vesical volume), bladder vesical pressure was 8.06 ± 1.5 mmHg and perfusate flow driven by a pressure gradient of 105 mmHg was 22.5 ± 2 mL/min (58.9 ± 7.8 mL/min-100 g). During filling, vesical pressure increased and flow decreased, but not necessarily in-parallel. Perfusate flow decreased transiently during isovolumetric contraction, and flow increased during emptying. A reduction in perfusion pressure from ∼105 to ∼40 mmHg reduced flow from ∼70 to ∼20 mL/min-100g, and reduced flow correlated with reduced vesical pressure. CONCLUSION: Perfusate flow is dependent on bladder perfusion pressure, and not necessarily reciprocally dependent on vesical pressure. Vesical pressure is highly sensitive to the level of perfusate flow, which supports the hypothesis that vesical pressure is dependent on the level of detrusor smooth muscle contractile activity (tone), and that compliance is dependent on bladder perfusion.

A study comparing videocapillaroscopy and dermoscopy in the assessment of nailfold capillaries in patients with systemic sclerosis-spectrum disorders.

OBJECTIVES: Nailfold videocapillaroscopy (NVC), the current gold standard for detection of capillary abnormalities suggestive of an SSc-spectrum disorder, is not widely available: a key question is whether lower-magnification, easy-to-use dermoscopy compares favourably. This is especially relevant given the inclusion of capillaroscopic abnormality within the 2013 classification criteria for SSc. Our objectives were to examine the ability to classify capillaries and to evaluate abnormality (severity), by both NVC and dermoscopy, to determine whether these differ between general and specialist rheumatologists, and to compare intra- and interrater reliability of both techniques. METHODS: NVC and dermoscopy images were acquired from all 10 nailbeds of 32 subjects with a range of capillary abnormalities. Images were graded (using a web-based interface) on a 0-3 scale of severity: normal (0), mildly (1), definitely (2) and grossly abnormal (3), and an unclassifiable category. Raters graded images from four subjects (40 nailbeds) using each technique, with five repeated images to estimate intrarater reliability. RESULTS: Forty-eight rheumatologists from 12 countries participated in the study (22 generalists, 26 specialists). While most images could be graded by both techniques, more were graded by NVC (84% vs 70%) and were systematically scored higher by NVC (mean difference 0.43 between the ratings). Agreement between the techniques was moderate. Intra- and interrater reliability were comparable for the two techniques in the classifiability of images and the grading of severity. CONCLUSION: Our results suggest that dermoscopy is comparable to NVC, although NVC images were more likely to be classifiable and were graded more severely.

Changes in the Perioperative Management and Outcomes of Patients With Upper Tract Urothelial Carcinoma Undergoing Radical Nephroureterectomy at Memorial Sloan Kettering Cancer Center: Over 20 Years of Experience.

INTRODUCTION: We evaluated surgical trends, perioperative management evolution, and oncologic outcomes in patients who underwent radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC) at a tertiary cancer center over a 24-year period. METHODS: Between 1995 and 2018, we evaluated 743 consecutive patients with UTUC who underwent RNU. Generalized additive models were used to estimate the associations between date of surgery and continuous outcomes using a linear model, dichotomous outcomes using a logit link, categorical outcomes using multinomial models, and 2- and 5-year survival outcomes using Cox proportional hazards models. RESULTS: Over the study period, preoperative diagnostic endoscopic biopsies increased from 10% to 66%, along with the proportion of patients who underwent RNU for high-grade disease from 55% to 91%. The rate of open RNU declined from 100% to 56% with a rise in minimally invasive approaches. Median lymph node yield increased with more retroperitoneal lymph node dissections performed. Neoadjuvant chemotherapy utilization increased with a contemporary utilization rate of 32%, coinciding with an increase in pT0 rate from 2% to 8%. Cancer-specific survival probabilities improved over the study period, while metastasis-free and overall survival remained stable. CONCLUSIONS: We found several changes in treatment patterns and outcomes for patients with UTUC over the past 2 decades. How individual alterations in management factors, such as patient selection, perioperative chemotherapy, lymphadenectomy, and salvage therapies, impact patient outcomes is challenging in the setting of multiple overlapping practice changes for this rare disease and warrants further investigation.

Race and Age-Related PSA Testing Disparities in Spinal Cord Injured Men: Analysis of National Veterans Health Administration Data.

Background: Prostate-specific antigen (PSA) testing remains controversial due to the debate about overdetection and overtreatment. Given the lack of published data regarding PSA testing rates in the population with spinal cord injury (SCI) within the US Department of Veterans Affairs (VA), there is concern for potential disparities and overtesting in this patient population. In this study, we sought to identify and evaluate national PSA testing rates in veterans with SCI. Methods: Using the VA Informatics and Computing Infrastructure Corporate Data Warehouse, we extracted PSA testing data for all individuals with a diagnosis of SCI. Testing rates were calculated, analyzed by race and age, and stratified according to published American Urological Association guideline groupings for PSA testing. Results: We identified 45,274 veterans at 129 VA medical centers with a diagnosis of SCI who had records of PSA testing in 2000 through 2017. Veterans who were only tested prior to SCI diagnosis were excluded. Final cohort data analysis included 37,243 veterans who cumulatively underwent 261,125 post-SCI PSA tests during the given time frame. Significant differences were found between African American veterans and other races veterans for all age groups (0.47 vs 0.46 tests per year, respectively, aged ≤ 39 years; 0.83 vs 0.77 tests per year, respectively, aged 40-54 years; 1.04 vs 1.00 tests per year, respectively, aged 55-69 years; and 1.08 vs 0.90 tests per year, respectively, aged ≥ 70 years; P < .001). Conclusions: Significant differences exist in rates of PSA testing in persons with SCI based on age and race. High rates of testing were found in all age groups, especially for African American veterans aged ≥ 70 years.

Impact of Metastasectomy on Cancer Specific and Overall Survival in Metastatic Renal Cell Carcinoma: Analysis of the REMARCC Registry.

BACKGROUND: Treatment paradigms for management of metastatic renal cell carcinoma (mRCC) are evolving. We examined impact of surgical metastasectomy on survival across in mRCC stratified by risk-group. METHODS: Multicenter retrospective analysis from the Registry of Metastatic RCC database. The cohort was subdivided utilizing Motzer criteria (favorable-, intermediate-, high-risk). Primary outcome was all-cause mortality (ACM)/overall survival (OS); secondary outcome was cancer-specific mortality (CSM)/cancer-specific survival (CSS). Impact of metastasectomy was analyzed via Cox-Regression analysis adjusting for potential prognostic variables and Kaplan-Meier analysis (KMA) within each risk-group. RESULTS: Four hundred thirty-one patients (59 favorable-risk, 274 intermediate-risk, 98 high-risk; median follow-up 27.2 months) were analyzed. Metastasectomy was performed in 22 (37%), 66 (24%), and 32 (16%) of favorable-, intermediate- and high-risk groups (P = .012). Median number of metastases at diagnosis differed significantly (favorable-risk 2, intermediate-risk 3.4, high-risk 5.1, P < .001). On Cox-regression, high-risk (HR = 1.72, P = .002) was associated with worsened ACM, while metastasectomy was associated with improved ACM (HR = 0.56, P = .005). On KMA, median OS (months) was longer with metastasectomy in favorable- (92.7 vs. 25.8, P = .003) and intermediate-risk (26.3 vs. 20.1, P = .038), but not high-risk (P = .911) groups. Metastasectomy was associated with longer CSS in favorable- (76.1 vs. 32.8, P = .004) but not intermediate- (P = .06) and high-risk (P = .595) groups. CONCLUSIONS: Metastasectomy was independently associated with improved ACM and CSM, as well as improved CSS and OS in favorable- and intermediate-risk mRCC patients. Metastasectomy may be considered as component of multimodal management strategy in favorable and intermediate-risk subgroups. In high-risk patients, metastasectomy should be deferred except in select circumstances.

Focal therapy for primary and salvage prostate cancer treatment: a narrative review.

Despite innovations in surgical technology and advancements in radiation therapy, radical treatments for clinically localized prostate cancer are associated with significant patient morbidity, including both urinary and sexual dysfunction. This has created a vital need for therapies and management strategies that provide an acceptable degree of oncologic efficacy while mitigating these undesirable side effects. Successful developments in screening approaches and advances in prostate imaging have allowed clinicians to identify, localize, and more precisely target early cancers. This has afforded urologists with an important opportunity to develop and employ focal ablation techniques that selectively destroy tumors while preserving the remainder of the gland, thus avoiding detrimental treatment effects to surrounding sensitive structures. A lack of high-level evidence supporting such an approach had previously hindered widespread adoption of focal treatments, but there are now numerous published clinical trials which have sought to establish benchmarks for safety and efficacy. As the clinical evidence supporting a potential role in prostate cancer treatment begins to accumulate, there has been a growing acceptance of focal therapy in the urologic oncology community. In this narrative review article, we describe the techniques, advantages, and side effect profiles of the most commonly utilized focal ablative techniques and analyze published clinical trial data supporting their evolving role in the prostate cancer treatment paradigm.

Metastatic melanoma to the bladder presenting as autonomic dysreflexia in a patient with paraplegia.

We report a case of a 66-year-old male with T2 American Spinal Injury Association Impairment Scale (AIS) A paraplegia who presented to Urology with worsening autonomic dysreflexia. Work-up identified a bladder mass treated by transurethral resection and pathologically confirmed as melanoma. Additional work-up revealed metastatic melanoma to the back and brain. The patient completely recovered with no evidence of disease more than two years after completing therapy. In this report, we review the presentation of metastatic bladder melanoma presenting with autonomic dysreflexia, which has never been previously described, and discuss the prognosis of metastatic melanoma to the bladder.

Patient-Derived Xenograft Models in Urological Malignancies: Urothelial Cell Carcinoma and Renal Cell Carcinoma.

The engraftment of human tumor tissues into immunodeficient host mice to generate patient-derived xenograft (PDX) models has become increasingly utilized for many types of cancers. By capturing the unique genomic and molecular properties of the parental tumor, PDX models enable analysis of patient-specific clinical responses. PDX models are an important platform to address the contribution of inter-tumoral heterogeneity to therapeutic sensitivity, tumor evolution, and the mechanisms of treatment resistance. With the increasingly important role played by targeted therapies in urological malignancies, the establishment of representative PDX models can contribute to improved facilitation and adoption of precision medicine. In this review of the evolving role of the PDX in urothelial cancer and kidney cancer, we discuss the essential elements of successful graft development, effective translational application, and future directions for clinical models.

Raman chemometric urinalysis (Rametrix) as a screen for bladder cancer.

Bladder cancer (BCA) is relatively common and potentially recurrent/progressive disease. It is also costly to detect, treat, and control. Definitive diagnosis is made by examination of urine sediment, imaging, direct visualization (cystoscopy), and invasive biopsy of suspect bladder lesions. There are currently no widely-used BCA-specific biomarker urine screening tests for early BCA or for following patients during/after therapy. Urine metabolomic screening for biomarkers is costly and generally unavailable for clinical use. In response, we developed Raman spectroscopy-based chemometric urinalysis (Rametrix™) as a direct liquid urine screening method for detecting complex molecular signatures in urine associated with BCA and other genitourinary tract pathologies. In particular, the RametrixTM screen used principal components (PCs) of urine Raman spectra to build discriminant analysis models that indicate the presence/absence of disease. The number of PCs included was varied, and all models were cross-validated by leave-one-out analysis. In Study 1 reported here, we tested the Rametrix™ screen using urine specimens from 56 consented patients from a urology clinic. This proof-of-concept study contained 17 urine specimens with active BCA (BCA-positive), 32 urine specimens from patients with other genitourinary tract pathologies, seven specimens from healthy patients, and the urinalysis control SurineTM. Using a model built with 22 PCs, BCA was detected with 80.4% accuracy, 82.4% sensitivity, 79.5% specificity, 63.6% positive predictive value (PPV), and 91.2% negative predictive value (NPV). Based on the number of PCs included, we found the RametrixTM screen could be fine-tuned for either high sensitivity or specificity. In other studies reported here, RametrixTM was also able to differentiate between urine specimens from patients with BCA and other genitourinary pathologies and those obtained from patients with end-stage kidney disease (ESKD). While larger studies are needed to improve RametrixTM models and demonstrate clinical relevance, this study demonstrates the ability of the RametrixTM screen to differentiate urine of BCA-positive patients. Molecular signature variances in the urine metabolome of BCA patients included changes in: phosphatidylinositol, nucleic acids, protein (particularly collagen), aromatic amino acids, and carotenoids.

Trifecta Outcomes of Partial Nephrectomy in Patients Over 75 Years Old: Analysis of the REnal SURGery in Elderly (RESURGE) Group.

BACKGROUND: Partial nephrectomy (PN) in elderly patients is underutilized with concerns regarding risk of complications and potential for poor outcomes. OBJECTIVE: To evaluate quality and functional outcomes of PN in patients >75 yr using trifecta as a composite outcome of surgical quality. DESIGN, SETTING, AND PARTICIPANTS: Multicenter retrospective analysis of 653 patients aged >75 yr who underwent PN (REnal SURGery in Elderly [RESURGE] Group). INTERVENTION: PN. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Primary outcome was achievement of trifecta (negative margin, no major [Clavien ≥3] urological complications, and ≥90% estimated glomerular filtration rate [eGFR] recovery). Secondary outcomes included chronic kidney disease (CKD) stage III and CKD upstaging. Multivariable analysis (MVA) was used to assess variables for achieving trifecta and functional outcomes. Kaplan-Meier survival analysis (KMA) was used to calculate renal functional outcomes. RESULTS AND LIMITATIONS: We analyzed 653 patients (mean age 78.4 yr, median follow-up 33 mo; 382 open, 157 laparoscopic, and 114 robotic). Trifecta rate was 40.4% (n=264). Trifecta patients had less transfusion (p<0.001), lower intraoperative (5.3% vs 27%, p<0.001) and postoperative (25.4% vs 37.8%, p=0.001) complications, shorter hospital stay (p=0.045), and lower ΔeGFR (p <0.001). MVA for predictive factors for trifecta revealed decreasing RENAL nephrometry score (odds ratio [OR] 1.26, 95% confidence interval 1.07-1.51, p=0.007) as being associated with increased likelihood to achieve trifecta. Achievement of trifecta was associated with decreased risk of CKD upstaging (OR 0.47, 95% confidence interval 0.32-0.62, p<0.001). KMA showed that trifecta patients had improved 5-yr freedom from CKD stage 3 (93.5% vs 57.7%, p<0.001) and CKD upstaging (84.3% vs 8.2%, p<0.001). Limitations include retrospective design. CONCLUSIONS: PN in elderly patients can be performed with acceptable quality outcomes. Trifecta was associated with decreased tumor complexity and improved functional preservation. PATIENT SUMMARY: We looked at quality outcomes after partial nephrectomy in elderly patients. Acceptable quality outcomes were achieved, measured by a composite outcome called trifecta, whose achievement was associated with improved kidney functional preservation.

Radical penectomy, a compromise for life: results from the PECAD study.

BACKGROUND: The use of organ sparing strategies to treat penile cancer (PC) is currently supported by evidence that has indicated the safety, efficacy and benefit of this surgery. However, radical penectomy still represents up to 15-20% of primary tumor treatments in PC patients. The aim of the study was to evaluate efficacy in terms of overall survival (OS) and disease-free survival (DFS) of radical penectomy in PC patients. METHODS: Data from a retrospective multicenter study (PEnile Cancer ADherence study, PECAD Study) on PC patients treated at 13 European and American urological centers (Hospital "Sant'Andrea", Sapienza University, Roma, Italy; "G.D'Annunzio" University, Chieti and ASL 2 Abruzzo, Hospital "S. Pio da Pietrelcina", Vasto, Italy; Department of Genitourinary Oncology, Moffitt Cancer Center, Tampa, FL, USA; Hospital of Budapest, Hungary; Department of Emergency and Organ Transplantation, Urology and Andrology Unit II, University of Bari, Italy; Hospital "Spedali Civili", Brescia, Italy; Istituto Europeo di Oncologia, University of Milan, Milan, Italy; University of Modena & Reggio Emilia, Modena, Italy; Hospital Universitario La Paz, Madrid, Spain; Ceara Cancer Institute, Fortaleza, Brazil; Virginia Commonwealth University, Richmond, VA, USA; Aristotle University of Thessaloniki, Thessaloniki, Greece; Maria Sklodowska-Curie Memorial Cancer Center, Warsaw, Poland) between 2010 and 2016 were used. Medical records of patients who specifically underwent radical penectomy were reviewed to identify main clinical and pathological variables. Kaplan-Meier method was used to estimate 1- and 5-year OS and DFS. RESULTS: Of the entire cohort of 425 patients, 72 patients (16.9%) treated with radical penectomy were extracted and were considered for the analysis. The median age was 64.5 (IQR, 57.5-73.2) years. Of all, 41 (56.9%) patients had pT3/pT4 and 31 (43.1%) pT1/pT2. Moreover, 36 (50.0%) were classified as pN1-3 and 5 (6.9%) M1. Furthermore, 61 (84.7%) had a high grade (G2-G3) with 6 (8.3%) positive surgical margins. The 1- and 5-year OS rates were respectively 73.3% and 59.9%, while the 1- and 5-year DFS rates were respectively 67.3% and 35.1%. CONCLUSIONS: PC is an aggressive cancer particularly in more advanced stage. Overall, more than a third of patients do not survive at 5 years and more than 60% report a disease recurrence, despite the use of a radical treatment.

Outcomes of minimally invasive partial nephrectomy among very elderly patients: report from the RESURGE collaborative international database.

The aim of the study was to perform a comprehensive investigation of clinical outcomes of robot-assisted partial nephrectomy (RAPN) or laparoscopic partial nephrectomy (LPN) in elderly patients presenting with a renal mass. The REnal SURGery in Elderly (RESURGE) collaborative database was queried to identify patients aged 75 or older diagnosed with cT1-2 renal mass and treated with RAPN or LPN. Study outcomes were: overall complications (OC); warm ischemia time (WIT) and 6-month estimated glomerular filtration rate (eGFR); positive surgical margins (PSM), disease recurrence (REC), cancer-specific mortality (CSM) and other-cause mortality (OCM). Descriptive statistics, Kaplan-Meier, smoothed Poisson plots and logistic and linear regression models (MVA) were used. Overall, 216 patients were included in this analysis. OC rate was 34%, most of them being of low Clavien grade. Median WIT was 17 minutes and median 6-month eGFR was 54 ml/min/1.73 m2. PSM rate was 5%. After a median follow-up of 20 months, the 5-year rates of REC, CSM and OCM were 4, 4 and 5%, respectively. At MVA predicting perioperative morbidity, RAPN relative to LPN (odds ratio [OR] 0.33; p <0.0001) was associated with lower OC rate. At MVA predicting functional outcomes, RAPN relative to LPN was associated with shorter WIT (estimate [EST] -4.09; p <0.0001), and with higher 6-month eGFR (EST 6.03; p = 0.01). In appropriately selected patients with small renal masses, minimally-invasive PN is associated with acceptable perioperative outcomes. The use of a robotic approach over a standard laparoscopic approach can be advantageous with respect to clinically relevant outcomes, and it should be preferred when available.

Bladder attack: transient bladder ischemia leads to a reversible decrease in detrusor compliance.

BACKGROUND: The deleterious effects of chronic ischemia on bladder function have been extensively studied; however, evaluation and characterization of the effects of acute ischemia and hypoxia are lacking. The present study examined pig and human detrusor smooth muscle (DSM) strips, in combination with an isolated perfused working pig bladder model to evaluate the relationship between transient ischemia and bladder function. METHODS: Organ bath and myographic studies were performed using pig and human DSM strips exposed to starvation/hypoxia conditions. Analogous conditions were then recreated in the ex vivo bladder preparation. Filled bladders were then treated with intravascular carbachol to induce contraction and subsequent void. An intravesical transducer continuously monitored changes in bladder pressure, while a tissue pO2 monitor analyzed changes in oxygenation. RESULTS: After 120 min in starved/hypoxic conditions, both pig and human DSM strips demonstrated significantly increased resting tone, with a greater than two-fold increase in force over control. This was effectively blocked with atropine. DSM strips also demonstrated significantly weaker contractions; however, contractile force was nearly recovered following 15-min exposure to replete/oxygenated buffer. In the ex vivo bladder preparation, filling under ischemic conditions yielded a 225% increase in end-fill vesical pressures (Pves) compared to controls. End-fill Pves returned to baseline with reperfusion during a subsequent filling cycle. CONCLUSIONS: Transient ischemia/hypoxia leads to an acute increase in tone in both DSM strips and ex vivo pig bladder. Remarkably, the effect is reversible with re-perfusion and may be blocked with anticholinergics, suggesting a relationship between acute ischemia and increased local acetylcholine release.