Urine Biopsy as Dynamic Biomarker to Enhance Clinical Staging of Bladder Cancer in Radical Cystectomy Candidates.

PURPOSE: There is significant interest in identifying complete responders to neoadjuvant chemotherapy (NAC) before radical cystectomy (RC) to potentially avoid removal of a pathologically benign bladder. However, clinical restaging after NAC is highly inaccurate. The objective of this study was to develop a next-generation sequencing-based molecular assay using urine to enhance clinical staging of patients with bladder cancer. METHODS: Urine samples from 20 and 44 patients with bladder cancer undergoing RC were prospectively collected for retrospective analysis for molecular correlate analysis from two clinical trials, respectively. The first cohort was used to benchmark the assay, and the second was used to determine the performance characteristics of the test as it correlates to responder status as measured by pathologic examination. RESULTS: First, to benchmark the assay, known mutations identified in the tissue (MT) of patients from the Accelerated Methotrexate, Vinblastine, Doxorubicin, Cisplatin trial (ClinicalTrials.gov identifier: NCT01611662, n = 16) and a cohort from University of California-San Francisco (n = 4) were cross referenced against mutation profiles from urine (MU). We then determined the correlation between MU persistence and residual disease in pre-RC urine samples from a second prospective clinical trial (The pT0 trial; ClinicalTrials.gov identifier: NCT02968732). Residual MU status correlated strongly with residual disease status (pT0 trial; n = 44; P = .0092) when MU from urine supernatant and urine pellet were assessed separately and analyzed in tandem. The sensitivity, specificity, PPV, and NPV were 91%, 50%, 86%, and 63% respectively, with an overall accuracy of 82% for this second cohort. CONCLUSION: MU are representative of MT and thus can be used to enhance clinical staging of urothelial carcinoma. Urine biopsy may be used as a reliable tool that can be further developed to identify complete response to NAC in anticipation of safe RC avoidance.

Risk of Secondary Malignancies After Pelvic Radiation: A Population-based Analysis.

Background and objective: Radiation therapy has increasingly been used in the management of pelvic malignancies. However, the use of radiation continues to pose a risk of a secondary malignancy to its recipients. This study investigates the risk of secondary malignancy development following radiation for primary pelvic malignancies. Methods: A retrospective cohort review of the Surveillance, Epidemiology, and End Results database from 1975 to 2016 was performed. Primary pelvic malignancies were subdivided based on the receipt of radiation, and secondary malignancies were stratified as pelvic or nonpelvic to investigate the local effect of radiation. Key findings and limitations: A total of 2 102 192 patients were analyzed (1 189 108 with prostate, 315 026 with bladder, 88 809 with cervical, 249 535 with uterine, and 259 714 with rectal/anal cancer). The incidence rate (defined as cases per 1000 person years) of any secondary malignancies (including but not limited to secondary pelvic malignancies) was higher in radiation patients than in nonradiation patients (incidence rate ratio [IRR] 1.04, confidence interval [CI] 1.03-1.05), with significantly greater rates noted in radiation patients with prostate (IRR 1.22, CI 1.21-1.24), uterine (IRR 1.34), and cervical (IRR 1.80, CI 1.72-1.88) cancer. While the overall incidence rate of any secondary pelvic malignancy was lower in radiation patients (IRR 0.79, CI 0.78-0.81), a greater incidence was still noted in the same cohorts including radiation patients with prostate (IRR 1.42, CI 1.39-1.45), uterine (IRR 1.15, CI 1.08-1.21), and cervical (IRR 1.72, CI 1.59-1.86) cancer. Conclusions and clinical implications: Except for localized cervical cancer, when put in the context of median overall survival, the impact of radiation likely does not carry enough weight to change practice patterns. Radiation for pelvic malignancies increases the risk for several secondary malignancies, and more specifically, secondary pelvic malignancies, but with a relatively low absolute risk of secondary malignancies, the benefits of radiation warrant continued use for most pelvic malignancies. Practice changes should be considered for radiation utilization in malignancies with excellent cancer-specific survival such as cervical cancer. Patient summary: The use of radiation for the management of pelvic malignancies induces a risk of secondary malignancies to its recipients. However, the absolute risk being low, the benefits of radiation warrant its continued use, and a change in practice patterns is unlikely.

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.

Multiparametric MRI is not sufficient for prostate cancer staging: A single institutional experience validated by a multi-institutional regional collaborative.

OBJECTIVE: Multiparametric magnetic resonance imaging (mpMRI) has been increasingly utilized in prostate cancer (CaP) diagnosis and staging. While Level 1 data supports MRI utility in CaP diagnosis, there is less data on staging utility. We sought to evaluate the real-world accuracy of mpMRI in staging localized CaP. MATERIALS AND METHODS: Men who underwent radical prostatectomy (RP) for CaP in 2021 at our institution were identified. Sensitivity, specificity, positive predictive value and negative predictive value of mpMRI in predicting pT2N0 organ confined disease , extracapsular extension , seminal vesicle invasion , lymph node involvement, and bladder neck invasion were evaluated. Associations between MRI accuracy and AUA risk stratification (AUA RS), MRI institution (MRI-I), MRI strength (1.5 vs. 3T) (MRI-S), and MRI timing (MRI-T) were assessed. These analyses were repeated using Pennsylvania Urologic Regional Collaborative (PURC) data. RESULTS: Institutional and community mpMRI CaP staging data demonstrated poor sensitivity (2.9%-49.2%% vs. 16.8%-24.4%), positive predictive value (40%-100% vs. 35.8%-68.2%), and negative predictive value (56.3%-94.3% vs. 68.4%-96.2%) in predicting surgical pathologic features - in contrast, specificity (89.1%-100% vs. 93.9%-98.6%) was adequate. mpMRI accuracy for extracapsular extension, seminal vesicle invasion, and lymph node involvement was significantly (p < 0.001) associated with AUA RS. There was no association between mpMRI accuracy and MRI-I, MRI-S, and MRI-T. CONCLUSION: Despite enthusiasm for its use, in a real-world setting, mpMRI appears to be a poor staging study for localized CaP and is unreliable as the sole means of staging patients prior to prostatectomy. mpMRI should be used cautiously as a staging tool for CaP, and should be interpreted considering individual patient risk strata.

The use of individualized 3D-printed models on trainee and patient education, and surgical planning for robotic partial nephrectomies.

3D printing is a growing tool in surgical education to visualize and teach complex procedures. Previous studies demonstrating the usefulness of 3D models as teaching tools for partial nephrectomy used highly detailed models costing between $250 and 1000. We aimed to create thorough, inexpensive 3D models to accelerate learning for trainees and increase health literacy in patients. Patient-specific, cost-effective ($30-50) 3D models of the affected urologic structures were created using pre-operative imaging of 40 patients undergoing partial nephrectomy at Thomas Jefferson University Hospital (TJUH) between July 2020 and May 2021. Patients undergoing surgery filled out a survey before and after seeing the model to assess patient understanding of their kidney, pathophysiology, surgical procedure, and risks of surgery. Three urological residents, one fellow, and six attendings filled out separate surveys to assess their surgical plan and confidence before and after seeing the model. In a third survey, they ranked how much the model helped their comprehension and confidence during surgery. Patient understanding of all four subjects significantly improved after seeing the 3D model (P < 0.001). The urology residents (P < 0.001) and fellow (P < 0.001) reported significantly increased self-confidence after interacting with the model. Attending surgeon confidence increased significantly after seeing the 3D model (P < 0.01) as well. Cost-effective 3D models are effective learning tools and assist with the evaluation of patients presenting with renal masses, and increase patient, resident, and fellow understanding in partial nephrectomies. Further research should continue to explore the utility of inexpensive models in other urologic procedures.

Volumetric Quantitative Contrast-enhanced Ultrasonography Evaluation of Complex Renal Cysts: An Adjunctive Metric to the Bosniak Classification System to Predict Malignancy.

BACKGROUND: Management of complex renal cysts is guided by the Bosniak classification system, which may be inadequate for risk stratification of patients for intervention. Fractional tumor vascularity (FV) calculated from volumetric contrast-enhanced ultrasound (CEUS) images may provide additional useful information. OBJECTIVE: To evaluate CEUS and FV calculation for risk stratification of patients with complex renal cysts. DESIGN, SETTING, AND PARTICIPANTS: This was a pilot prospective study with institutional review board approval involving patients undergoing surgery for Bosniak IIF-IV complex renal cysts. CEUS was performed preoperatively on the day of surgery with two-dimensional (2D) and three-dimensional (3D) imaging and sulfur hexafluoride lipid-type A microspheres as the ultrasound contrast agent. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: A custom MATLAB program was used to select regions of interest on CEUS scans. FV was calculated according to FV = 1 - (total nonenhancing area/total lesion area). We assessed the ability of 2D- and 3D-derived percentage FV (2DFV%, and 3DFV%) and Bosniak classification schemes (pre-2019 [P2019B] and post-2019 [B2019]) to predict malignancy, aggressive histology, and upstaging on surgical pathology. Performance was assessed as area under the receiver operating characteristic curve (AUC). RESULTS AND LIMITATIONS: Twenty eligible patients were included in final analysis, of whom 85% (n = 17) had Bosniak IV cysts and 85% (n = 17) had malignant disease on final pathology. Four (24%) of the malignant lesions were International Society of Urological Pathology grade 3-4. The AUC for predicting malignancy was 0.980, 0.824, 0.863, and 0.824 with P2019B, B2019, 2DFV%, and 3DFV%, respectively. When the Bosniak classification was combined with FV%, three models had an AUC of 1, while the combined 2DFV% + B2019 model had AUC of 0.980. CONCLUSIONS: FV is a novel metric for evaluating complex cystic renal masses and enhances the ability of the Bosniak classification system to predict malignancy. This metric may serve as an adjunct in risk stratification for surgical intervention. Further prospective evaluation is warranted. PATIENT SUMMARY: Cysts in the kidney are currently classified using a scheme called the Bosniak system. We assessed measurement of the percentage of vascular tissue (called fractional vascularity) in cysts on a special type of ultrasound scan. This promising test adds information when combined with the Bosniak system and can help in guiding appropriate treatment.

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.

IL-15 Superagonist NAI in BCG-Unresponsive Non-Muscle-Invasive Bladder Cancer.

BACKGROUND: Patients with Bacillus Calmette­Guérin (BCG)­unresponsive non­muscle-invasive bladder cancer (NMIBC) have limited treatment options. The immune cell­activating interleukin-15 (IL-15) superagonist Nogapendekin alfa inbakicept (NAI), also known as N-803, may act synergistically with BCG to elicit durable complete responses (CRs) in this patient population. METHODS: In this open-label, multicenter study, patients with BCG-unresponsive bladder carcinoma in situ (CIS) with or without Ta/T1 papillary disease were treated with intravesical NAI plus BCG (cohort A) or NAI alone (cohort C). Patients with BCG-unresponsive high-grade Ta/T1 papillary NMIBC also received NAI plus BCG (cohort B). The primary end point was the incidence of CR at the 3- or 6-month assessment visit for cohorts A and C, and the disease-free survival (DFS) rate at 12 months for cohort B. Durability, cystectomy avoidance, progression-free survival, disease-specific survival (DSS), and overall survival were secondary end points for cohort A. RESULTS: In cohort A, CR was achieved in 58 (71%) of 82 patients (95% confidence interval [CI]=59.6 to 80.3; median follow-up, 23.9 months), with a median duration of 26.6 months (95% CI=9.9 months to [upper bound not reached]). At 24 months in patients with CR, the Kaplan­Meier estimated probability of avoiding cystectomy and of DSS was 89.2% and 100%, respectively. In cohort B (n=72), the Kaplan­Meier estimated DFS rate was 55.4% (95% CI=42.0% to 66.8%) at 12 months, with median DFS of 19.3 months (95% CI=7.4 months to [upper bound not reached]). Most treatment-emergent adverse events for patients receiving BCG plus NAI were grade 1 to 2 (86%); three grade 3 immune-related treatment-emergent adverse events occurred. CONCLUSIONS: In patients with BCG-unresponsive bladder carcinoma in situ and papillary NMIBC treated with BCG and the novel agent NAI, CRs were achieved with a persistence of effect, cystectomy avoidance, and 100% bladder cancer­specific survival at 24 months. The study is ongoing, with an estimated target enrollment of 200 participants (Funded by ImmunityBio.)

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.

Technology-enhanced AcceleRation of Germline Evaluation for Therapy (TARGET): A randomized controlled trial of a pretest patient-driven webtool vs. genetic counseling for prostate cancer germline testing.

BACKGROUND: Germline testing has an increasingly important role in prostate cancer care. However, a relative shortage of genetic counselors necessitates alternate strategies for delivery of pre-test education for germline testing. This study, funded by the Prostate Cancer Foundation, seeks to address the need for novel methods of delivery of pre-test germline education beyond traditional germline counseling to facilitate informed patient decision-making for germline testing. METHODS: This is a two-armed randomized controlled trial (RCT) with a target enrollment of 173 participants with prostate cancer per study arm (total anticipated n = 346). Patients who meet criteria for germline testing based on tumor features, family history or Ashkenazi Jewish ancestry are being recruited from 5 US sites including academic, private practice and Veterans healthcare settings. Consenting participants are randomized to the interactive pretest webtool or germline counseling with assessment of key patient-reported outcomes involved in informed decision-making for germline testing. RESULTS: Participants complete surveys at baseline, after pretest education/counseling, and following disclosure of germline results. The primary outcome of the study is decisional conflict for germline testing. Secondary outcomes include genetic knowledge, satisfaction, uptake of germline testing, and understanding of results. CONCLUSION: Our hypothesis is that the web-based genetic education tool is non-inferior to traditional genetic counseling regarding key patient-reported outcomes involved in informed decision-making for germline testing. If proven, the results would support deploying the webtool across various practice settings to facilitate pre-test genetic education for individuals with prostate cancer and developing collaborative care strategies with genetic counseling. CLINICALTRIALS: gov Identifier: NCT04447703.

Helix: A Digital Tool to Address Provider Needs for Prostate Cancer Genetic Testing in Clinical Practice.

BACKGROUND: Prostate cancer (PCA) germline testing (GT) is now standard-of-care for men with advanced PCA. Thousands of men may consider GT due to clinical and family history (FH) features. Identifying and consenting men for GT can be complex. Here we identified barriers and facilitators of GT across a spectrum of providers which informed the development of Helix - an educational and clinical/FH collection tool to facilitate GT in practice. MATERIALS AND METHODS: A 12-question survey assessing knowledge of genetics PCA risk and FH was administered December 2017 to March 2018 in the Philadelphia area and at the Mid-Atlantic AUA meeting (March 2018). Responses were analyzed using descriptive statistics. Semi-structured interviews were conducted with medical oncologists, radiation oncologists, and urologists across practice settings from March-October 2020 as part of a larger study based on the Tailored Implementation in Chronic Diseases framework. Helix was then developed followed by user testing. RESULTS: Fifty-six providers (50% urologists) responded to the survey. Multiple FH and genetic knowledge gaps were identified: only 66% collected maternal FH and 43% correctly identified BRCA2 and association to aggressive PCA. Genetic counseling gaps included low rates of discussing genetic discrimination laws (45%). Provider interviews (n = 14) identified barriers to FH intake including access to details and time needed. In user testing (n = 10), providers found Helix helpful for FH collection. All providers found Helix easy to use, suggesting expanded clinical use. CONCLUSION: Helix addressed multiple GT knowledge and practice gaps across a spectrum of providers. This tool will become publicly available soon to facilitate PCA GT in clinical practice.

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.

Salvage Low-Dose-Rate Prostate Brachytherapy: Clinical Outcomes of a Phase 2 Trial for Local Recurrence after External Beam Radiation Therapy (NRG Oncology/RTOG 0526).

PURPOSE: We report efficacy of a prospective phase 2 trial (NCT00450411) of salvage low-dose-rate (LDR) prostate brachytherapy (BT) for local failure (LF) after prior external beam radiation therapy (EBRT) with minimum 5-years' follow-up. METHODS AND MATERIALS: Eligible patients had low/intermediate risk prostate cancer (PCa) before EBRT and biopsy-proven LF >30 months after EBRT, with prostate-specific antigen <10 ng/mL and no regional/distant disease. The primary endpoint, late gastrointestinal and genitourinary adverse events (Common Terminology Criteria for Adverse Events v3.0) grade ≥3 were 14%. With minimum 5-year follow-up after salvage BT, secondary clinical outcomes including disease-free survival (DFS; includes death from any cause), disease-specific survival, and overall survival (OS) were estimated using the Kaplan-Meier method and modelled using Cox proportional hazards regression. Local tumor progression (ie, LF), distant failure (DF), and biochemical failure (BF) were estimated using cumulative incidence. Time to LF, DF, and BF were modeled by cause-specific Cox proportional hazards regression. RESULTS: From May 2007 to January 2014, 20 centers registered 100 patients (92 analyzable). Median follow-up is 6.7 years (range, 0.3-11.2); median age 70 years (range, 55-82); median prior EBRT dose 74 Gy [interquartile range (IQR):70 - 76] at a median of 85 months prior (IQR 60-119 months). Androgen deprivation was combined with salvage BT in 16%. Ten-year OS is 70% [95% confidence interval (CI) 58% - 83%]. Nineteen patients died (5 PCa, 10 other, 4 unknown). Ten-year failure rates are local 5% (95% CI, 1-11), distant 19% (95% CI, 10-29), and biochemical 46% (95% CI, 34-57). DFS is 61% at 5 years and 33% at 10 years. No baseline characteristic was significantly associated with any clinical outcome. CONCLUSIONS: This is the first prospective multicenter trial reporting outcomes of salvage LDR BT for LF after EBRT. Five-year freedom from BF is 68%, comparable to other salvage modalities. Although further LF is rare (5%), BF climbs to 46% by 10 years.

Pretest Genetic Education Video Versus Genetic Counseling for Men Considering Prostate Cancer Germline Testing: A Patient-Choice Study to Address Urgent Practice Needs.

PURPOSE: Germline testing (GT) for prostate cancer (PCA) is now central to treatment and hereditary cancer assessment. With rising demand for and shortage of genetic counseling (GC), tools to deliver pretest informed consent across practice settings are needed to improve access to GT and precision care. Here, we report on Evaluation and Management for Prostate Oncology, Wellness, and Risk (EMPOWER), a patient-choice study for pretest video-based genetic education (VBGE) versus GC to inform urgent practice needs. PATIENTS AND METHODS: Men with PCA or at risk for PCA (family history of PCA) were eligible and could choose pretest VBGE or GC. Outcomes included decisional conflict for GT, change in genetics knowledge, satisfaction, and intention to share results with family and/or providers. Descriptive statistics summarized results with counts and percentages for categorical variables and mean ± standard deviation for continuous variables. Data were compared with Fisher's exact, chi-squared, or Wilcoxon two-sample tests. Mean change in genetics knowledge was compared with t tests. The significance level was set a priori at .05. RESULTS: Data on the first 127 participants were analyzed. Characteristics were White (85.8%), bachelor's degree (66.9%), and PCA diagnosis (90.6%). The majority chose VBGE (71%) versus GC (29%; P < .001). No differences were observed in decisional conflict for GT or satisfaction. Cancer genetics knowledge improved in both groups without significant difference (+0.9 VBGE, +1.8 GC, P = .056). Men who chose VBGE had higher intention to share GT results (96.4% VBGE v 86.4% GC, P = .02). Both groups had high rates of GT uptake (VBGE 94.4%, GC 92%). CONCLUSION: A substantial proportion of men opted for pretest VBGE, with comparable patient-reported outcomes and uptake of GT. The results support the use of pretest video to address the critical GC shortage in the precision era.

Outcomes of Active Surveillance for Men With Intermediate Risk Prostate Cancer: A Population-Based Analysis.

OBJECTIVE: To assesses if active surveillance (AS) is an appropriate treatment modality for patients with intermediate risk (IR) prostate cancer (PCa) utilizing population-level data to compare the survival outcomes of men with low risk (LR) and IR PCa initially treated with AS, watchful waiting (WW) or active treatment (AT). METHODS: In total, 166,244 patients were initially identified in the surveillance, epidemiology, and end results database using biopsy Gleason grade group (GG) alone-GG1 and GG2. In total, 94,891 patients with GG1 and GG2 disease were further stratified by National Comprehensive Cancer Network risk categories-LR, favorable IR (fIR), and unfavorable IR (uIR). Predictors of cancer-specific (CSS) and overall survival (OS) were analyzed, stratified by risk classification and initial treatment-AT (first-line curative surgery or radiotherapy), AS or WW, utilizing the new "Watchful waiting recode (2010+)" variable. RESULTS: We found GG2 patients on AS had worse CSS and OS than GG2 patients who received AT and GG1 patients treated with AS or AT; these trends persist within the National Comprehensive Cancer Network fIR and uIR cohorts. WW patients (GG1, GG2, LR, fIR, and uIR) had the worst survival outcomes of any cohort (log-rank tests P < .05). CONCLUSIONS: We demonstrate a significantly worse 5-year CSS and OS for men with GG2, fIR, and uIR PCa treated with AS compared to AT. Our analysis suggests that AS should not be the preferred treatment modality for IR PCa.

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.

Preventing Prostate Biopsy Complications: to Augment or to Swab?

OBJECTIVE: To use data from a large, prospectively- acquired regional collaborative database to compare the risk of infectious complications associated with three American Urologic Association- recommended antibiotic prophylaxis pathways, including culture-directed or augmented antibiotics, following prostate biopsy. METHODS: Data on prostate biopsies and outcomes were collected from the Pennsylvania Urologic Regional Collaborative, a regional quality collaborative working to improve the diagnosis and treatment of prostate cancer. Patients were categorized as receiving one of three prophylaxis pathways: culture-directed, augmented, or provider-discretion. Infectious complications included fever, urinary tract infections or sepsis within one month of biopsy. Odds ratios of infectious complication by pathway were determined, and univariate and multivariate analyses of patient and biopsy characteristics were performed. RESULTS: 11,940 biopsies were included, 120 of which resulted in infectious outcomes. Of the total biopsies, 3246 used "culture-directed", 1446 used "augmented" and 7207 used "provider-discretion" prophylaxis. Compared to provider-discretion, the culture-directed pathway had 84% less chance of any infectious outcome (OR= 0.159, 95% CI = [0.074, 0.344], P < 0.001). There was no difference in infectious complications between augmented and provider-discretion pathways. CONCLUSIONS: The culture-directed pathway for transrectal prostate biopsy resulted in significantly fewer infectious complications compared to other prophylaxis strategies. Tailoring antibiotics addresses antibiotic-resistant bacteria and reduces future risk of resistance. These findings make a strong case for incorporating culture-directed antibiotic prophylaxis into clinical practice guidelines to reduce infection following prostate biopsies.