The evolving role of contrast-enhanced ultrasound in urology: a review.

PURPOSE: Ultrasound's versatility and ease of use has expanded its application in many clinical settings. Technological advancements with contrast-enhanced ultrasound (CEUS) have allowed high quality imaging similar to CT or MRI with lower risk of contrast toxicity and radiation exposure. In this review article we examine the development of CEUS and its vast applications in the field of urology. METHODS: A PubMed literature search was performed using keywords: contrast enhanced ultrasound, prostate cancer, renal cancer, and multiparametric ultrasound. RESULTS: The development of CEUS has improved transrectal ultrasound imaging with increased detection of prostate cancer (PCa). Further enhancements of CEUS such as subharmonic imaging (SHI), flash replenishment imaging (FRI) and contrast ultrasound dispersion imaging (CUDI) allow improved PCa diagnosis. CEUS has also emerged as an important tool in characterizing suspicious renal mass without compromising renal function with contrast imaging. CONCLUSION: CEUS has modernized imaging and diagnosis of prostate and renal cancer. Future advancements and utilization of CEUS will allow its expansion into other urological subspecialties.

Enhancing bladder cancer care through the multidisciplinary clinic approach.

INTRODUCTION: To report the impact of our 25-year multidisciplinary care delivery model experience on patients with muscle invasive bladder cancer treated at our National Cancer Institute (NCI)-designated Sidney Kimmel Cancer Center at Jefferson University. To our knowledge, our multidisciplinary genitourinary cancer clinic (MDC) is the longest continuously operating center of its kind at an NCI Cancer Center in the United States. MATERIALS AND METHODS: We selected a recent group of patients with cT2-4 N0-1 M0 bladder cancer seen in the Sidney Kimmel Cancer Center Genitourinary Oncology MDC from January 2016 to September 2019. These patients were identified retrospectively. SEER-18 (Surveillance, Epidemiology, and End Results) database, November 2019 submission was queried to obtain patients with similarly staged disease diagnosed between 2015 and 2017. Completion rates of radical cystectomy, use of neoadjuvant therapies, and survival outcomes were compared between the two cohorts. RESULTS: Ninety-one patients from the MDC form this time period were identified; 65.9% underwent radical cystectomy and 71.8% received neoadjuvant therapy in the form of chemotherapy, immune checkpoint inhibition or a combination of the two - higher than reported national trends for neoadjuvant therapies. Progression of disease was seen in 24.2% of patients. A total of 8675 patients met inclusion criteria in the SEER database. Rates of radical cystectomy were significantly higher in MCD patients when compared to SEER derived data (65.9% vs. 37.7%, p =< 0.001). MCD patients had significantly better cancer-specific survival (mean 20.4 vs. 18.3 months p = 0.028, median survival not reached). CONCLUSION: Our long term experience caring for patients with genitourinary malignancies such as bladder cancer in a uniform multidisciplinary team results in a high utilization of neoadjuvant therapies. When compared to a contemporary SEER-derived cohort, multidisciplinary patients were more likely to undergo radical cystectomy and had longer cancer-specific survival.

Contrast-Enhanced Ultrasound and Shear Wave Elastography: Novel Methods for the Evaluation of Urethral Stricture Disease.

PURPOSE: Urologists will benefit from an imaging modality which can assess intra and extraluminal characteristics of urethral strictures. We conducted a prospective pilot study evaluating the utility of contrast-enhanced ultrasound and shear wave elastography for the evaluation of bulbar urethral stricture disease. MATERIALS AND METHODS: Patients with a single, bulbar urethral stricture were prospectively recruited. Contrast-enhanced ultrasound and shear wave elastography were performed at the time of surgical repair and at 4 months' followup using an Aplio i800 scanner (Canon Medical Systems, Tustin, California) with an i8CX1 transducer. Sulfur hexafluoride lipid-type A microsphere ultrasound contrast (Lumason®, Bracco Imaging, Princeton, New Jersey) was injected retrograde through the urethra. Stiffness of the corpus spongiosum was measured at and adjacent to the stricture site. Stricture lengths based on retrograde urethrogram, grayscale ultrasound and contrast-enhanced ultrasound were correlated with measured intraoperative stricture length. RESULTS: Thirty men were enrolled. Contrast-enhanced ultrasound (R2=0.709) showed the best correlation with intraoperative measured stricture length compared to retrograde urethrogram (R2=0.016) or grayscale ultrasound (R2=0.471). Stiffness of the spongiosum was greater at the site of the stricture (32.6±5.4 vs 27.3±5.8 kPa, p=0.044) and in narrower caliber strictures (p=0.044) but did not differ by stricture length (p=0.182). At followup (4.3±1.1 months) contrast-enhanced ultrasound detected stricture recurrence with 80% sensitivity, 100% specificity, and 93% accuracy compared to cystoscopy. CONCLUSIONS: This pilot study demonstrates the ability of contrast-enhanced ultrasound and shear wave elastography to become safe, accurate, and potentially efficacious modalities for assessing bulbar urethral strictures and spongiofibrosis.

Does antithrombotic use enable earlier diagnosis of bladder cancer? A brief institutional assessment.

INTRODUCTION: Wallis et al (JAMA 2017) demonstrated use of antithrombotic medications (ATMs) is associated with increased prevalence of hematuria-related complications and subsequent bladder cancer diagnosis within 6 months. Stage of diagnosis was lacking in this highly publicized study. This study examined the association of ATM use on bladder cancer stage at the time of diagnosis. MATERIALS AND METHODS: We completed a retrospective chart review of patients with a bladder cancer diagnosis at our institution. Patient demographics and bladder cancer work up information were assessed. Patients were stratified based on use of ATMs at time diagnosis. Descriptive statistics were completed to identify association between ATM use and stage of bladder cancer diagnosis, as stratified by non-muscle invasive bladder cancer (NMIBC) versus muscle invasive bladder cancer (MIBC). RESULTS: A total of 1052 patient charts were reviewed. Eight hundred and forty-four were included and 208 excluded due to unavailability of diagnosis history. At diagnosis, 357 (42.3%) patients were taking ATMs. Patients on ATMs presented with NMIBC at similar rates as patients not taking ATMs (81.2% vs. 77.8%, p = 0.23). Subgroup analysis by ATM class similarly demonstrated no statistically significant differences in staging. CONCLUSION: While Wallis et al established that patients on blood thinners who present with hematuria are more likely to be diagnosed with genitourinary pathology, this factor does not appear to enable an earlier diagnosis of bladder cancer. Future study may assess hematuria at presentation (gross, microscopic), type of blood thinners, and low versus high risk NMIBC presentation.

Imaging urothelial bladder cancer: A VPAC PET targeted approach.

INTRODUCTION Accurate staging of urothelial bladder cancer (UBC) with imaging, which guides effective bladder cancer treatment, remains challenging. This investigation is to validate a hypothesis that targeting Vasoactive intestinal and pituitary adenylate cyclase activating peptide (VPAC) receptors using 64Cu-TP3805 can PET image UBC efficiently. MATERIALS AND METHODS: Nineteen patients (44-84 years of age) scheduled for radical cystectomy, underwent VPAC positron emission tomography (PET) imaging prior to surgery. Sixteen had completed neoadjuvant chemotherapy prior to imaging. All 19 received 64Cu-TP3805 (148 % ± 10% MBq) intravenously, and were imaged 60 to 90 minutes later. Standard uptake value (SUV)max for malignant lesions and SUVmean for normal tissues were determined and mean +/-SEM recorded. Following radical cystoprostatectomy, pelvic lymphadenectomy and urinary diversion imaging, results were compared with final surgical pathology. RESULTS: 64Cu-TP3805 had no adverse events, negligible urinary excretion and rapid blood clearance. UBC PET images for residual disease were true positive in 11 patients and true negative in four. Of remaining 4, one had false positive and 3 had false negative scans, equating to 79% sensitivity (95%, CI 49%-95%), 80% specificity (95%, CI 28%-100%), 92% positive predictive value (95%, CI 62%-100%) and 57% negative predictive value (95%, CI 18%-90%). CONCLUSIONS: These first in man results, in a group, heavily pretreated with neoadjuvant chemotherapy, indicate that VPAC PET imaging can identify UBC effeiciently and suggest, that VPAC PET can diagnose UBC in a treatment naïve cohort for accurate staging, guide biopsy and treatment in patients with suspected metastasis and determine response to therapy. Further investigation of this molecular imaging approach is warranted.

Effects of Contrast-Enhanced Ultrasound of Indeterminate Renal Masses on Patient Clinical Management: Retrospective Analysis From 2 Institutions.

OBJECTIVES: To investigate the long-term impact of contrast-enhanced ultrasound (CEUS) on the treatment of patients with indeterminate renal masses. METHODS: In this retrospective study, consecutive charts of all patients receiving renal CEUS at 1 of 2 academic medical centers between January 1, 2014, and December 31, 2018, were reviewed. Patients were included in the study if they had documented chronic renal disease (estimated glomerular filtration rate < 60 mL/min/1.73 m2 ) or prior nephrectomy and received CEUS for a previously untreated renal mass. RESULTS: A total of 215 lesions in 157 patients were used for analysis. Contrast-enhanced ultrasound provided a final treatment recommendation in 71.6% of lesions (154 of 215). Of these 154 lesions, 7.8% (12 of 154) were lost to follow-up despite CEUS suggesting malignancy; 15.6% (24 of 154) went directly for surgical intervention, with malignancy confirmed by pathologic results in 87.5% (21 of 24) of these cases; and the remaining 76.6% (118 of 154) were deemed benign and required no additional follow-up. Of the 118 lesions diagnosed by CEUS as benign and requiring no follow-up, none showed evidence of later renal cell carcinoma development and, only 5.1% (6 of 118) of the total population was referred for further cross-sectional imaging of the mass in question. In 28.4% of all lesions (61 of 215), CEUS resulted in a recommendation for surveillance imaging at a 6- to 12-month interval, and less than 10% (6 of 61) of these underwent additional cross-sectional imaging within the recommended 6 months after CEUS. CONCLUSIONS: These findings highlight the impact of CEUS on clinical treatment of indeterminate renal masses, including reducing the use of the potentially nephrotoxic contrast agents and providing a direct pathway to transplant.

Phase II Trial of Neoadjuvant Systemic Chemotherapy Followed by Extirpative Surgery in Patients with High Grade Upper Tract Urothelial Carcinoma.

PURPOSE: Data supporting neoadjuvant chemotherapy of high grade upper tract urothelial carcinoma are scant. In this multi-institution, prospective, phase II trial we investigated pathological complete responses after neoadjuvant chemotherapy of high grade upper tract urothelial carcinoma. MATERIALS AND METHODS: Patients with high grade upper tract urothelial carcinoma in whom nephroureterectomy was planned were assigned to 4 neoadjuvant chemotherapy cycles of accelerated methotrexate, vinblastine, doxorubicin and cisplatin in those with baseline creatinine clearance greater than 50 ml per minute or gemcitabine and carboplatin in those with creatinine clearance 30 to 50 ml per minute or less. The study primary end point was a pathological complete response (ypT0N0). The accrual goal was 30 patients per arm. An 18% pathological complete response was considered worth further study while a 4% pathological complete response would not have justified pursuing this regimen. With 28 eligible patients per arm success was defined as 3 or more pathological complete responses (10.7%) in a given arm. Secondary end points included safety, renal function and oncologic outcomes. RESULTS: A total of 30 patients enrolled in the accelerated methotrexate, vinblastine, doxorubicin and cisplatin arm from 2015 to 2017. Six patients enrolled in the gemcitabine and carboplatin arm, which closed due to poor accrual. Of the 29 patients eligible for accelerated methotrexate, vinblastine, doxorubicin and cisplatin, including 23 men and 6 women with a median age of 65 years (range 40 to 84), 80% completed all planned treatments, 3 (10.3%) achieved ypT0N0 and 1 achieved ypT0Nx for a pathological complete response in 13.8% (90% CI 4.9-28.8). In 1 patient receiving accelerated methotrexate, vinblastine, doxorubicin and cisplatin nephroureterectomy was deferred due to grade 4 sepsis. The grade 3-4 toxicity rate was 23% in the accelerated methotrexate, vinblastine, doxorubicin and cisplatin arm with no grade 5 event. CONCLUSIONS: Accelerated methotrexate, vinblastine, doxorubicin and cisplatin neoadjuvant chemotherapy in patients with high grade upper tract urothelial carcinoma and creatinine clearance greater than 50 ml per minute was safe and demonstrated predefined activity with a 14% pathological complete response rate. Final pathological stage ypT1 or less in more than 60% of patients is encouraging. Together the results of this prospective trial support the use of neoadjuvant chemotherapy in eligible patients with high grade upper tract urothelial carcinoma.

Hospital-specific antibiograms and antibiotic prophylaxis for prostate biopsies: a reexamination of AUA recommendations.

INTRODUCTION: To assess whether standard American Urological Association (AUA) and other recommendations for prostate biopsy prophylaxis provide sufficient coverage of common urinary organisms responsible for post biopsy infections by comparing local antibiograms in Philadelphia-area hospitals. MATERIALS AND METHODS: De-identified culture results derived from antibiograms were collected from six academic and community hospitals in the Philadelphia region. Analysis specifically focused on four major bacterial causes of urinary tract infection following prostate biopsy (Escherichia coli (E. coli), Klebsiella pneumoniae, Proteus mirabilis and Enterococcus faecalis) along with commonly recommended antibiotics including fluoroquinolones (FQ's), trimethoprim/sulfamethoxazole, ceftriaxone, and gentamicin. RESULTS: Bacterial sensitivities to each antibiotic across institutions showed variation in E.coli sensitivities to FQs (p < 0.001), trimethoprim/sulfamethoxazole (p < 0.001), ceftriaxone (p < 0.001) and gentamicin (p < 0.001). Klebsiella pneumoniae and Proteus mirabilis exhibited similar variations. Sensitivity comparisons for Enterococcus faecalis was unable to be performed due to absent or incomplete data across institutions. CONCLUSION: Institutional antibiograms vary within our regional hospitals. Standardized recommendations for commonly used antibiotic prophylaxis such as fluoroquinolones may be inadequate for peri-procedural prostate biopsy prophylaxis based on local resistance patterns. Valuable information about the potential effectiveness of antibiotic prophylaxis for prostate biopsies can be found in local institutional antibiograms, and should be consulted when considering antibiotic prophylaxis for prostate biopsy procedures.

Simple frameshifts in minimally invasive surgery postoperative pain management significantly reduce opiate prescriptions.

INTRODUCTION: To evaluate the impact of an 'opt-in' non-narcotic postoperative pain regimen on narcotic utilization and patient-reported pain scores. MATERIALS AND METHODS: A prospective, non-blinded pre- and post-interventional trial was conducted, including a lead-in period for baseline evaluation. The intervention group received a new pain protocol prioritizing non-narcotic medications, an 'opt-in' requirement for opiates, and standardized patient education. Study outcomes included opiate prescription and utilization (measured in Morphine Equivalent Doses) and reported pain scores on postoperative day (POD) 1, discharge and follow up. RESULTS: At discharge, 70% fewer patients were prescribed any opioids (ARR: -0.7; p < 0.001); the amount prescribed was reduced by 95% (pre-intervention 69.3 mg versus post-intervention 3.5 mg, p < 0.001). Mean opioids used following discharge decreased by 76% (14.7 mg versus 3.5 mg, p = 0.011). In a subgroup analysis of robotic prostatectomies, there was a 95% reduction in mean opioids prescribed at discharge (64.6 mg versus 3.2 mg, p < 0.001) and 82% reduction in utilization over entire postoperative course (87.6 mg versus 15.7 mg, p = 0.001). There was no significant difference in pain scores between intervention groups at POD 1, discharge and follow up for patients (entire cohort and post-prostatectomy). CONCLUSION: A standardized pain protocol with 'opt-in' requirements for opiate prescription, emphasis on non-narcotic medications, and patient education, resulted in significant reductions in opioid use. Simple frameshifts in pain management can yield significant gains in the opioid epidemic.

Superb Microvascular Imaging Improves Detection of Vascularity in Indeterminate Renal Masses.

OBJECTIVES: Vascular assessment of indeterminate renal masses (iRMs) remains a crucial element of diagnostic imaging, as the presence of blood flow within renal lesions suggests malignancy. We compared the utility of Superb Microvascular Imaging (SMI; Canon Medical Systems, Tustin, CA), a novel Doppler technique, to standard color Doppler imaging (CDI) and power Doppler imaging (PDI) for the detection of vascularity within iRMs. METHODS: Patients undergoing contrast-enhanced ultrasound (CEUS) evaluations for iRMs first underwent a renal ultrasound examination with the following modes: CDI, PDI, color Superb Microvascular Imaging (cSMI), and monochrome Superb Microvascular Imaging (mSMI), using an Aplio i800 scanner with an i8CX1 transducer (Canon Medical Systems). After image randomization, each mode was assessed for iRM vascularity by 4 blinded readers on a diagnostic confidence scale of 1 to 5 (5 = most confident). The results were compared to CEUS as the reference standard. RESULTS: Forty-one patients with 50 lesions met inclusion criteria. Relative to the other 3 modalities, mSMI had the highest sensitivity (63.3%), whereas cSMI had the highest specificity (62.1%). Both cSMI and mSMI also had the highest diagnostic accuracy (0.678 and 0.680, respectively; both P < 0.001) compared to CDI (0.568) and PDI (0.555). Although the reader-reported confidence interval of mSMI (mean ± SD, 3.6 ± 1.1) was significantly lower than CDI (4.1 ± 1.0) and PDI (4.0 ± 1.0; P < 0.001), the confidence level of cSMI (4.1 ± 0.9) was not (P > 0.173). CONCLUSIONS: Preliminary data suggest that SMI is a potentially useful modality in detecting microvasculature in iRMs compared to standard Doppler techniques. Future studies should aim to compare the efficacy of both SMI and CEUS and to assess the ability of SMI to characterize malignancy in iRMs.

Active Surveillance as Initial Management of Newly Diagnosed Prostate Cancer: Data from the PURC.

PURPOSE: We describe contemporary active surveillance utilization and variation in a regional prostate cancer collaborative. We identified demographic and disease specific factors associated with active surveillance in men with newly diagnosed prostate cancer. MATERIALS AND METHODS: We analyzed data from the PURC (Pennsylvania Urologic Regional Collaborative), a cooperative effort of urology practices in southeastern Pennsylvania and New Jersey. We determined the rates of active surveillance among men with newly diagnosed NCCN® (National Comprehensive Cancer Network®) very low, low or intermediate prostate cancer and compared the rates among participating practices and providers. Univariate and multivariable analyses were used to identify factors associated with active surveillance utilization. RESULTS: A total of 1,880 men met inclusion criteria. Of the men with NCCN very low or low risk prostate cancer 57.4% underwent active surveillance as the initial management strategy. Increasing age was significantly associated with active surveillance (p <0.001) while adverse clinicopathological variables were associated with decreased active surveillance use. Substantial variation in active surveillance utilization was observed among practices and providers. CONCLUSIONS: More than 50% of men with low risk disease in the PURC collaborative were treated with active surveillance. However, substantial variation in active surveillance rates were observed among practices and providers in academic and community settings. Advanced age and favorable clinicopathological factors were strongly associated with active surveillance. Analysis of regional collaboratives such as the PURC may allow for the development of strategies to better standardize treatment in men with prostate cancer and offer active surveillance in a more uniform and systematic fashion.

Overlapping surgeries: defining the 'critical portions' of the procedure.

INTRODUCTION: An important aspect of overlapping surgery is to determine the 'critical portion' of an operation. Currently, there are no guidelines that standardize the critical portions of common urologic procedures. We sought to determine the relationship between the critical portions of common urologic operations as defined by the primary surgeon compared to the trainee at a single academic medical center. MATERIALS AND METHODS: In an open-ended survey of the Urology Department at Thomas Jefferson University, attending surgeons and urology residents, were asked to list five of their most commonly performed surgeries and subsequently identify what they defined as the critical portion for each. Responses were examined for surgeon-trainee congruence. Response agreement was defined as identifying key words that provided reasonable evidence that the responders were referring to identical portions of the case. RESULTS: Nine residents and eight attending physicians provided 67 and 63 responses, respectively, encompassing 28 different procedures. Six procedures were chosen for further analysis based on high volume of responses. Overall, of the 67 resident-reported critical portions, 32 (47.8%) were in agreement with attending-reported critical portions. Year of training in residency was not a predictor of surgeon-trainee agreement. CONCLUSION: External pressures from the public and lawmakers alike may demand that providers be present during all 'critical portions' of a procedure. Our study shows that the understanding of critical portions of an operation is often incongruent between surgeons and trainees. Critical portions of all procedures should be established by the surgical team in order to accurately schedule overlapping surgeries.

VPAC1-targeted PET/CT scan: improved molecular imaging for the diagnosis of prostate cancer using a novel cell surface antigen.

PURPOSE: Current approaches to prostate cancer screening and diagnosis are plagued with limitations in diagnostic accuracy. There is a compelling need for biomolecular imaging that will not only detect prostate cancer early but also distinguish prostate cancer from benign lesions accurately. In this topic paper, we review evidence that supports further investigation of VPAC1-targeted PET/CT imaging in the primary diagnosis of prostate cancer. METHODS: A non-systematic review of Medline/PubMed was performed. English language guidelines on prostate cancer diagnosis and management, original articles, and review articles were selected based on their clinical relevance. RESULTS: VPAC1 receptors were overexpressed 1000 times more in prostate cancer than benign prostatic stromal tissue. In vitro and in vivo studies showed that Copper-64 labeled analogs of VPAC1 ligands can be synthesized with high radiochemical efficiency and purity. The radioactive probes had excellent VPAC1 receptor binding specificity and affinity. They had good biochemical stability in vitro and in mouse and human serum. They had minimal urinary excretion, which made them favorable for prostate cancer imaging. Initial feasibility study in men with prostate cancer showed that the probes were safe with no reported adverse reaction. 64Cu-TP3805 PET/CT detected 98% of prostate cancer lesions and nodal metastasis as confirmed with whole mount histopathological evaluation. CONCLUSIONS: VPAC1 receptors are promising targets for biomolecular imaging of primary prostate cancer that can distinguish malignant from benign lesions non-invasively. Further investigations are warranted to validate initial findings and define the clinical utilities of VPAC1-targeted PET imaging for prostate cancer diagnosis and management.

Decision Support and Shared Decision Making About Active Surveillance Versus Active Treatment Among Men Diagnosed with Low-Risk Prostate Cancer: a Pilot Study.

This study aimed to explore the effects of a decision support intervention (DSI) and shared decision making (SDM) on knowledge, perceptions about treatment, and treatment choice among men diagnosed with localized low-risk prostate cancer (PCa). At a multidisciplinary clinic visit, 30 consenting men with localized low-risk PCa completed a baseline survey, had a nurse-mediated online DS session to clarify preference for active surveillance (AS) or active treatment (AT), and met with clinicians for SDM. Participants also completed a follow-up survey at 30 days. We assessed change in treatment knowledge, decisional conflict, and perceptions and identified predictors of AS. At follow-up, participants exhibited increased knowledge (p < 0.001), decreased decisional conflict (p < 0.001), and more favorable perceptions of AS (p = 0.001). Furthermore, 25 of the 30 participants (83 %) initiated AS. Increased family and clinician support predicted this choice (p < 0.001). DSI/SDM prepared patients to make an informed decision. Perceived support of the decision facilitated patient choice of AS.

Decipher test impacts decision making among patients considering adjuvant and salvage treatment after radical prostatectomy: Interim results from the Multicenter Prospective PRO-IMPACT study.

BACKGROUND: Patients with prostate cancer and their providers face uncertainty as they consider adjuvant radiotherapy (ART) or salvage radiotherapy (SRT) after undergoing radical prostatectomy. The authors prospectively evaluated the impact of the Decipher test, which predicts metastasis risk after radical prostatectomy, on decision making for ART and SRT. METHODS: A total of 150 patients who were considering ART and 115 who were considering SRT were enrolled. Providers submitted a management recommendation before processing the Decipher test and again at the time of receipt of the test results. Patients completed validated surveys on prostate cancer (PCa)-specific decisional effectiveness and PCa-related anxiety. RESULTS: Before the Decipher test, observation was recommended for 89% of patients considering ART and 58% of patients considering SRT. After Decipher testing, 18% (95% confidence interval [95% CI], 12%-25%) of treatment recommendations changed in the ART arm, including 31% among high-risk patients; and 32% (95% CI, 24%-42%) of management recommendations changed in the salvage arm, including 56% among high-risk patients. Decisional Conflict Scale (DCS) scores were better after viewing Decipher test results (ART arm: median DCS before Decipher, 25 and after Decipher, 19 [P<.001]; SRT arm: median DCS before Decipher, 27 and after Decipher, 23 [P<.001]). PCa-specific anxiety changed after Decipher testing; fear of PCa disease recurrence in the ART arm (P = .02) and PCa-specific anxiety in the SRT arm (P = .05) decreased significantly among low-risk patients. Decipher results reported per 5% increase in 5-year metastasis probability were associated with the decision to pursue ART (odds ratio, 1.48; 95% CI, 1.19-1.85) and SRT (odds ratio, 1.41; 95% CI, 1.09-1.81) in multivariable logistic regression analysis. CONCLUSIONS: Knowledge of Decipher test results was associated with treatment decision making and improved decisional effectiveness among men with PCa who were considering ART and SRT. Cancer 2017;123:2850-59. © 2017 American Cancer Society.

Development of a voided urine assay for detecting prostate cancer non-invasively: a pilot study.

OBJECTIVE: To validate a hypothesis that prostate cancer can be detected non-invasively by a simple and reliable assay by targeting genomic VPAC receptors expressed on malignant prostate cancer cells shed in voided urine. PATIENTS/SUBJECTS AND METHODS: VPAC receptors were targeted with a specific biomolecule, TP4303, developed in our laboratory. With an Institutional Review Board exempt approval of use of de-identified discarded samples, an aliquot of urine collected as a standard of care, from patients presenting to the urology clinic (207 patients, 176 men and 31 women, aged ≥21 years) was cytospun. The cells were fixed and treated with TP4303 and 4,6-diamidino-2-phenylindole (DAPI). The cells were then observed under a microscope and cells with TP4303 orange fluorescence around the blue (DAPI) nucleus were considered 'malignant' and those only with a blue nucleus were regarded as 'normal'. VPAC presence was validated using receptor blocking assay and cell malignancy was confirmed by prostate cancer gene profile examination. RESULTS: The urine specimens were labelled only with gender and presenting diagnosis, with no personal health identifiers or other clinical data. The assay detected VPAC positive cells in 98.6% of the men with a prostate cancer diagnosis (141), and none of the 10 men with benign prostatic hyperplasia. Of the 56 'normal' patients, 62.5% (35 patients, 10 men and 25 women) were negative for VPAC cells; 19.6% (11, 11 men and no women) had VPAC positive cells; and 17.8% (10, four men and six women) were uninterpretable due to excessive crystals in the urine. Although data are limited, the sensitivity of the assay was 99.3% with a confidence interval (CI) of 96.1-100% and the specificity was 100% with a CI of 69.2-100%. Receptor blocking assay and fluorescence-activated cell sorting (FACS) analyses demonstrated the presence of VPAC receptors and gene profiling examinations confirmed that the cells expressing VPAC receptors were malignant prostate cancer cells. CONCLUSION: These preliminary data are highly encouraging and warrant further evaluation of the assay to serve as a simple and reliable tool to detect prostate cancer non-invasively.

Preoperative nomogram to predict the likelihood of complications after radical nephroureterectomy.

OBJECTIVES: To construct a nomogram based on preoperative variables to better predict the likelihood of complications occurring within 30 days of radical nephroureterectomy (RNU). PATIENTS AND METHODS: The charts of 731 patients undergoing RNU at eight academic medical centres between 2002 and 2014 were reviewed. Preoperative clinical, demographic and comorbidity indices were collected. Complications occurring within 30 days of surgery were graded using the modified Clavien-Dindo scale. Multivariate logistic regression determined the association between preoperative variables and post-RNU complications. A nomogram was created from the reduced multivariate model with internal validation using the bootstrapping technique with 200 repetitions. RESULTS: A total of 408 men and 323 women with a median age of 70 years and a body mass index of 27 kg/m2 were included. A total of 75% of the cohort was white, 18% had an Eastern Cooperative Oncology Group (ECOG) performance status ≥2, 20% had a Charlson comorbidity index (CCI) score >5 and 50% had baseline chronic kidney disease (CKD) ≥ stage III. Overall, 279 patients (38%) experienced a complication, including 61 events (22%) with Clavien grade ≥ III. A multivariate model identified five variables associated with complications, including patient age, race, ECOG performance status, CKD stage and CCI score. A preoperative nomogram incorporating these risk factors was constructed with an area under curve of 72.2%. CONCLUSIONS: Using standard preoperative variables from this multi-institutional RNU experience, we constructed and validated a nomogram for predicting peri-operative complications after RNU. Such information may permit more accurate risk stratification on an individual cases basis before major surgery.

Fluorescence in situ hybridization (FISH) in the diagnosis of bladder and upper tract urothelial carcinoma: the largest single-institution experience to date.

INTRODUCTION: We evaluated the UroVysion (Abbott Molecular, IL, USA) fluorescence in situ hybridization (FISH) assay for the diagnosis of urothelial cancer in patients diagnosed with or suspected to have bladder, upper tract urothelial carcinoma (UTUC), and combined upper and lower tract urothelial carcinoma (BC). MATERIALS AND METHODS: A single institution retrospective analysis comparing sensitivity, specificity, positive predictive value, and negative predictive values for FISH and urinary cytology. FISH within 6 months of endoscopic evaluation were obtained from outpatient voided urine samples. Our institutional pathology department confirmed pathologic disease from specimens obtained during endoscopic evaluations for lower tract disease. For upper tract disease, disease was confirmed by retrograde ureteroscopy, biopsies of visual lesions, and site-specific upper tract cytology. RESULTS: A total of 415 patients submitted FISH specimens. Overall, FISH was more sensitive than cytology 54.9% in comparison with cytology 42.2% (p = 0.01), specificity favored cytology 92.9% compared to 73.5% with FISH (p < 0.01). For BC only patients, the same significant finding of increased sensitivity and decreased specificity was identified, but for UTUC alone and combined UTUC and BC, there was no significant difference. Cytology had improved positive predictive value (PPV) over FISH, 76.9% in comparison to 64.6% (p = 0.02). Negative predictive value (NPV) also favored cytology 74.2% versus 64.9% (p = 0.02). When analyzing individual cohorts, cytology had improved PPV for BC alone patients. UTUC showed no difference for PPV and NPV. For both UTUC and BC, NPV was slightly favored for FISH over cytology 93.2% versus 91.2% (p = 0.03). CONCLUSIONS: Voided urine FISH testing does offer a higher detection of urothelial carcinoma for BC compared to voided cytology; however, specificity was worse. FISH does not appear to improve detection of urothelial carcinoma in patients with either UTUC only or both BC and UTUC.

Prevalence and Characteristics of Patients with Suspected Inherited Renal Cell Cancer: Application of the ACMG/NSGC Genetic Referral Guidelines to Patient Cohorts.

Patients with suspected hereditary renal cell cancer (RCC) are under-referred for genetic evaluation. Characterizing the prevalence and characteristics of suspected inherited RCC is a crucial step toward advancing personalized, genetically-based cancer risk management for patients and their families. To evaluate the prevalence and characteristics of suspected inherited RCC syndromes based on consensus criteria, we performed a cross-sectional analysis of patients with a diagnosis of RCC in SEER (2001-2011, n = 105,754) and in our institutional cancer registry (2004-2013, n = 998). Consensus criteria for referral of patients with RCC for genetic evaluation from the American College of Medical Genetics and Genomics and National Society of Genetic Counselors (ACMG/NSGC) were applied to the two cohorts. The associations between meeting referral criteria with demographic characteristics were assessed with chi-square tests. Overall, 24.0 % of the SEER cohort and 33.7 % of our institutional cohort met ACMG/NSGC referral criteria for genetic counseling. While white patients more commonly met early onset clear cell RCC criteria, black patients met papillary RCC criteria at twice the rate of whites in both cohorts (p < 0.0001). As many as 1 in 5 individuals with RCC meet referral criteria for genetic evaluation based on newly emerging guidelines, with differences in pathology noted by race. Prospective genetic testing studies utilizing emerging referral guidelines should help to refine the genetic spectrum of inherited kidney cancer. This study supports efforts to increase awareness of referral of patients with RCC for genetic counseling particularly among urologic providers.