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Background: Our goal is to review current literature regarding the role of multi-parametric magnetic resonance imaging (mpMRI) in the active surveillance (AS) of prostate cancer (PCa) and identify trends in rate of reclassification of risk category, performance of fusion biopsy (FB) versus systematic biopsy (SB), and progression-free survival., Methods: We performed a comprehensive literature search in PubMed and identified 121 articles. A narrative summary was performed., Results: Thirty-two articles were chosen to be featured in this review. SB and FB are complementary in detecting higher-grade disease in follow-up. While FB was more likely than SB to detect clinically significant disease, FB missed 6.4-11% of clinically significant disease. Imaging factors that predicted upgrading include number of lesions on magnetic resonance imaging (MRI), lesion density, and MRI suspicion level., Conclusion: Incorporating mpMRI FB in conjunction with SB should be part of contemporary AS protocols. mpMRI should additionally be used routinely for follow-up; however, mpMRI is not currently sensitive enough in detecting disease progression to replace biopsy in the surveillance protocol., Competing Interests: Competing Interests: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s), 2022.)

Objective: To describe our technique of robot-assisted synchronous bilateral nephrectomy (RASBN) for autosomal dominant polycystic kidney disease (ADPKD)., Methods: Given prior abdominal surgery/transplant in most patients, we prefer an open cut-down access to place a 12 mm port 10 cm infraumbilically. Four (8 mm) robotic ports are then placed under vision in a fan distribution along the umbilical level. The operating table is placed in reverse Trendelenburg and tilted opposite to the targeted side. Provided there are no concerns for malignancy, some cysts encountered in large kidneys (>2.5 L) may require puncture, to facilitate access and mobilization. The resected kidney is placed in a large bag and tucked in the pelvis. A similar procedure is carried out on the contralateral side after redocking the robot and tilting the table in the opposite direction. The specimen bags are extracted by elongating the lower midline 12 mm port site., Results: Seven cases of RASBN performed for ADPKD were identified (December 2015 to December 2018). Median (interquartile range, IQR) values for patient demographics were: Age = 59 years (47-63), body mass index = 29 (26-32), and American Society of Anaesthesiology grade = 3. Three patients had prior deceased- and 4 had prior living- donor transplants. Indication for nephrectomy were: pain (5), hemorrhage into cysts (3), and renal masses (2). Perioperative outcomes were: operating room time = 388 minutes, estimated blood loss = 200 mL, hemoglobin change = 1.3 g/dL, transfusion = 0, length of hospital stay = 3 days, Grade I Clavien-Dindo complications = 2 cases. All patients were alive at a median follow-up of 3.8 years., Conclusion: RASBN is safe and effective in ADPKD even in the context of prior renal transplant patients with attendant comorbidities., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Introduction: The use of volume-rendered images is gaining popularity in the surgical planning for complex procedures. IRIS™ is an interactive software that delivers three-dimensional (3D) virtual anatomical models. We aimed to evaluate the preoperative clinical utility of IRIS for patients with ≤T2 localized renal tumors who underwent either partial nephrectomy (PN) or radical nephrectomy (RN). Patients and Methods: Six urologists (four faculty and two trainees) reviewed CT scans of 40 cases over 2 study phases, using conventional two-dimensional (2D) CT alone (Phase-I), followed by the CT + IRIS 3D model (Phase-II). After each review, surgeons reported their decision on performing a PN or an RN and rated (Likert scale) their confidence in completing the procedure as well as how the imaging modality influenced specific procedural decisions. Modifications to the choice of procedure and confidence in decisions between both phases were compared for the same surgeon. Concordance between surgeons was also evaluated. Results: A total of 462 reviews were included in the analysis (231 in each phase). In 64% (95% CI: 58-70%) of reviews, surgeons reported that IRIS achieved a better spatial orientation, understanding of the anatomy, and offered additional information compared with 2D CT alone. IRIS impacted the planned procedure in 20% of the reviews (3.5% changed decision from PN to RN and 16.5% changed from RN to PN). In the remaining 80% of reviews, surgeons' confidence increased from 78% (95% CI: 72-84%) with 2D CT, to 87% (95% CI: 82-92%) with IRIS ( p  = 0.02); this confidence change was more pronounced in cases with a high RENAL score ( p  = 0.009). In 99% of the reviews, surgeons rated that the IRIS accurately represented the anatomical details of all kidney components. Conclusion: Application of IRIS 3D models could influence the surgical decision-making process and improve surgeons' confidence, especially for robot-assisted management of complex renal tumors.

Objectives: To incorporate and validate clinically relevant performance metrics of simulation (CRPMS) into a hydrogel model for nerve-sparing robot-assisted radical prostatectomy (NS-RARP)., Materials and Methods: Anatomically accurate models of the human pelvis, bladder, prostate, urethra, neurovascular bundle (NVB) and relevant adjacent structures were created from patient MRI by injecting polyvinyl alcohol (PVA) hydrogels into three-dimensionally printed injection molds. The following steps of NS-RARP were simulated: bladder neck dissection; seminal vesicle mobilization; NVB dissection; and urethrovesical anastomosis (UVA). Five experts (caseload >500) and nine novices (caseload <50) completed the simulation. Force applied to the NVB during the dissection was quantified by a novel tension wire sensor system fabricated into the NVB. Post-simulation margin status (assessed by induction of chemiluminescent reaction with fluorescent dye mixed into the prostate PVA) and UVA weathertightness (via a standard 180-mL leak test) were also assessed. Objective scoring, using Global Evaluative Assessment of Robotic Skills (GEARS) and Robotic Anastomosis Competency Evaluation (RACE), was performed by two blinded surgeons. GEARS scores were correlated with forces applied to the NVB, and RACE scores were correlated with UVA leak rates., Results: The expert group achieved faster task-specific times for nerve-sparing (P = 0.007) and superior surgical margin results (P = 0.011). Nerve forces applied were significantly lower for the expert group with regard to maximum force (P = 0.011), average force (P = 0.011), peak frequency (P = 0.027) and total energy (P = 0.003). Higher force sensitivity (subcategory of GEARS score) and total GEARS score correlated with lower nerve forces (total energy in Joules) applied to NVB during the simulation with a correlation coefficient (r value) of -0.66 (P = 0.019) and -0.87 (P = 0.000), respectively. Both total and force sensitivity GEARS scores were significantly higher in the expert group compared to the novice group (P = 0.003). UVA leak rate highly correlated with total RACE score r value = -0.86 (P = 0.000). Mean RACE scores were also significantly different between novices and experts (P = 0.003)., Conclusion: We present a realistic, feedback-driven, full-immersion simulation platform for the development and evaluation of surgical skills pertinent to NS-RARP. The correlation of validated objective metrics (GEARS and RACE) with our CRPMS suggests their application as a novel method for real-time assessment and feedback during robotic surgery training. Further work is required to assess the ability to predict live surgical outcomes., (© 2019 The Authors BJU International © 2019 BJU International Published by John Wiley & Sons Ltd.)

Background: Multiparametric magnetic resonance imaging (mpMRI) for prostate cancer detection without careful patient selection may lead to excessive resource utilization and costs., Objective: To develop and validate a clinical tool for predicting the presence of high-risk lesions on mpMRI., Design, Setting, and Participants: Four tertiary care centers were included in this retrospective and prospective study (BiRCH Study Collaborative). Statistical models were generated using 1269 biopsy-naive, prior negative biopsy, and active surveillance patients who underwent mpMRI. Using age, prostate-specific antigen, and prostate volume, a support vector machine model was developed for predicting the probability of harboring Prostate Imaging Reporting and Data System 4 or 5 lesions. The accuracy of future predictions was then prospectively assessed in 214 consecutive patients., Outcome Measurements and Statistical Analysis: Receiver operating characteristic, calibration, and decision curves were generated to assess model performance., Results and Limitations: For biopsy-naïve and prior negative biopsy patients (n=811), the area under the curve (AUC) was 0.730 on internal validation. Excellent calibration and high net clinical benefit were observed. On prospective external validation at two separate institutions (n=88 and n=126), the machine learning model discriminated with AUCs of 0.740 and 0.744, respectively. The final model was developed on the Microsoft Azure Machine Learning platform (birch.azurewebsites.net). This model requires a prostate volume measurement as input., Conclusions: In patients who are naïve to biopsy or those with a prior negative biopsy, BiRCH models can be used to select patients for mpMRI., Patient Summary: In this multicenter study, we developed and prospectively validated a calculator that can be used to predict prostate magnetic resonance imaging (MRI) results using patient age, prostate-specific antigen, and prostate volume as input. This tool can aid health care professionals and patients to make an informed decision regarding whether to get an MRI., (Copyright © 2018 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Background: Prostate multiparametric magnetic resonance imaging (mpMRI) may be recommended for patients with a prior negative systematic biopsy (SB). However, a proportion of these patients will continue to have no prostate cancer (PCa) identified on magnetic resonance/ultrasound fusion biopsy (FB) despite abnormal mpMRI findings., Methods: In this multi-institutional, retrospective study, clinical and mpMRI parameters were assessed for 285 consecutive patients with at least 1 prior negative biopsy who underwent FB for a Prostate Imaging Reporting and Data System (PI-RADS) score of 3 to 5 at the University of Rochester Medical Center from December 2014 to December 2016, or at the University of Alabama at Birmingham from February 2014 to February 2017. Nomograms were generated for predicting benign prostate pathology on both the targeted biopsy and the concurrent SB., Results: Benign pathology was found in 132 of 285 patients (46.3%). In a multivariate analysis, the predictors of benign prostate pathology on FB were age, prostate-specific antigen, prostate volume, and PI-RADS score. The predicted probabilities were plotted on a receiver operating characteristic curve, and the area under the curve was 0.825. The nomogram demonstrated excellent calibration and a high net benefit in a decision curve analysis. With a theoretical cutoff probability of ≥0.7 used to recommend deferment of FB, 61 of 285 patients (21.4%) would have avoided an unnecessary biopsy, and only 4 of 285 patients (1.4%) with PCa with a Gleason score ≥ 3 + 4 would have been missed., Conclusions: False-positive mpMRI examinations may occur in up to 46.3% of patients with a prior negative biopsy. Thus, a multi-institutional nomogram has been developed and validated for predicting benign pathology after FB in patients with a prior negative biopsy, and this may help to reduce the number of unnecessary biopsies in the setting of abnormal mpMRI findings. Cancer 2018;124:278-85. © 2017 American Cancer Society., (© 2017 American Cancer Society.)

Purpose: Recently a large body of evidence has emerged indicating that cribriform morphology is an aggressive prostate cancer morphological pattern associated with higher cancer specific mortality. In a comprehensive analysis we compared traditional and contemporary prostate biopsy techniques to detect prostate cancer with cribriform morphology with radical prostatectomy serving as the reference standard., Materials and Methods: We queried a retrospectively maintained, single institution, multiparametric magnetic resonance imaging database of 1,001 patients to identify 240 who underwent magnetic resonance imaging-ultrasound fusion targeted biopsy and concurrent systematic biopsy from December 2014 to December 2016. Of the 3,978 biopsy cores obtained 694 positive cores were rereviewed by a genitourinary pathologist for pattern 4 subtype (cribriform, fused and poorly formed glands). Using paired analysis pathological results among 3 biopsy methods (systematic biopsy, targeted biopsy and systematic plus targeted biopsy) were compared. Prostatectomy specimens were also pathologically reviewed., Results: Systematic plus targeted biopsy was superior to systematic biopsy alone or targeted biopsy alone to detect cribriform morphology (all p <0.0001). On final histopathology cribriform tumor foci were associated with an increased percent of pattern 4 involvement and extraprostatic extension (p <0.0001 and 0.003, respectively). Only 17.4% of cribriform tumors in pure form were visible on multiparametric magnetic resonance imaging. Based on final histopathology the sensitivity of systematic biopsy, targeted biopsy and systematic plus targeted biopsy for cribriform morphology was 20.7%, 28.6% and 37.1%, respectively., Conclusions: Although systematic plus targeted biopsy was the most accurate biopsy method to detect cribriform morphology, biopsy sensitivity and specificity remained poor., (Copyright © 2018 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Purpose: We determined whether Gleason pattern 4 architecture impacts tumor visibility on multiparametric magnetic resonance imaging and correlates with final histopathology., Materials and Methods: A total of 83 tumor foci were identified in 22 radical prostatectomy specimens from patients with a prior negative biopsy who underwent magnetic resonance/ultrasound fusion biopsy followed by radical prostatectomy from January 2015 to July 2016. A genitourinary pathologist rereviewed tumor foci for Gleason architectural subtype. Each prostate imaging reporting and data system category 3 to 5 lesion on multiparametric magnetic resonance imaging was paired with its corresponding pathological tumor focus. Univariable and multivariable analyses were performed to determine predictors of tumor visibility., Results: Of the 83 tumor foci identified 26 (31%) were visible on multiparametric magnetic resonance imaging, 33 (40%) were Gleason score 3+3 and 50 (60%) were Gleason score 3+4 or greater. Among tumor foci containing Gleason pattern 4, increasing tumor size and noncribriform predominant architecture were the only independent predictors of tumor detection on multivariable analysis (p = 0.002 and p = 0.011, respectively). For tumor foci containing Gleason pattern 4, 0.5 cm or greater, multiparametric magnetic resonance imaging detected 10 of 13 (77%), 5 of 14 (36%) and 9 of 10 (90%) for poorly formed, cribriform and fused architecture, respectively (p = 0.01). The size threshold for the detection of cribriform tumors was higher than that of other architectural patterns. Furthermore, cribriform pattern was identified more frequently on systematic biopsy than on targeted biopsy., Conclusions: Reduced visibility of cribriform pattern on multiparametric magnetic resonance imaging has significant ramifications for prostate cancer detection, surveillance and focal therapy., (Copyright © 2017 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Background: The Prostate Cancer Prevention Trial Risk Calculator 2.0 (PCPTRC) is a widely used risk-based calculator used to assess a man's risk of prostate cancer (PCa) before biopsy. This risk calculator was created from data of a patient cohort undergoing a 6-core sextant biopsy, and subsequently validated in men undergoing 12-core systematic biopsy (SBx). The accuracy of the PCPTRC has not been studied in patients undergoing magnetic resonance imaging/ultrasound (MRI/US) fusion-guided biopsy (FBx). We sought to assess the performance of the PCPTRC for straitifying PCa risk in a FBx cohort., Methods: A review of a prospective cohort undergoing MRI and FBx/SBx was conducted. Data from consecutive FBx/SBx were collected between August 2007 and February 2014, and PCPTRC scores using the PCPTRC2.0R-code were calculated. The risk of positive biopsy and high-grade cancer (Gleason ⩾7) on biopsy was calculated and compared with overall and high-grade cancer detection rates (CDRs). Receiver operating characteristic curves were generated and the areas under the curves (AUCs) were compared using DeLong's test., Results: Of 595 men included in the study, PCa was detected in 39% (232) by SBx compared with 48% (287) on combined FBx/SBx biopsy. The PCPTRC AUCs for the CDR were similar (P=0.70) for SBx (0.69) and combined biopsy (0.70). For high-grade disease, AUCs for SBx (0.71) and combined biopsy (0.70) were slightly higher, but were not statistically different (P=0.55)., Conclusions: In an MRI-screened population of men undergoing FBx, PCPTRC continues to represent a practical method of accurately stratifying PCa risk.

Use of transrectal ultrasound guided systematic prostate biopsy has poor diagnostic accuracy for prostate cancer (PCa) detection. Recently multiparametric MRI (mpMRI) of the prostate and MR/US fusion biopsy has been gaining popularity for men who have previously undergone a negative biopsy. We performed PubMed ® and Web of Science ® searches to identify studies on this subject, particularly focusing on studies consisting of patients who have had at least one previously negative biopsy. Across the literature, when a suspicious lesion is found on mpMRI, MR/US fusion biopsy has consistently demonstrated higher detection rate for any PCa and clinically significant PCa (csPCa) compared to the traditional repeat systematic biopsy (SB) approach. Furthermore, anteriorly located tumors are frequently identified using MR targeted biopsy (TB), suggesting that an MR guided approach allows for increased accuracy for detecting tumors commonly missed by systematic biopsies. We conclude that men with a prior negative biopsy and continued suspicion of PCa should strongly be encouraged to get a prostate mpMRI prior to a repeat biopsy., Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare.

Purpose: Active surveillance is an established option for men with low risk prostate cancer. Multiparametric magnetic resonance imaging with magnetic resonance imaging-transrectal ultrasound fusion guided biopsy may better identify patients for active surveillance compared to systematic 12-core biopsy due to improved risk stratification. To our knowledge the performance of multiparametric magnetic resonance imaging in following men on active surveillance with visible lesions is unknown. We evaluated multiparametric magnetic resonance imaging and magnetic resonance imaging-transrectal ultrasound fusion guided biopsy to monitor men on active surveillance., Materials and Methods: This retrospective review included men from 2007 to 2015 with prostate cancer on active surveillance in whom magnetic resonance imaging visible lesions were monitored by multiparametric magnetic resonance imaging and fusion guided biopsy. Progression was defined by ISUP (International Society of Urological Pathology) grade group 1 to 2 and ISUP grade group 2 to 3. Significance was considered at p ≤0.05., Results: A total of 166 patients on active surveillance with 2 or more fusion guided biopsies were included in analysis. Mean followup was 25.5 months. Of the patients 29.5% had pathological progression. Targeted biopsy alone identified 44.9% of patients who progressed compared to 30.6% identified by systematic 12-core biopsy alone (p = 0.03). Fusion guided biopsy detected 26% more cases of pathological progression on surveillance biopsy compared to systematic 12-core biopsy. Progression on multiparametric magnetic resonance imaging was the sole predictor of pathological progression at surveillance biopsy (p = 0.013). Multiparametric magnetic resonance imaging progression in the entire cohort had 81% negative predictive value, 35% positive predictive value, 77.6% sensitivity and 40.5% specificity in detecting pathological progression., Conclusions: Multiparametric magnetic resonance imaging progression predicts the risk of pathological progression. Patients with stable multiparametric magnetic resonance imaging findings have a low rate of progression. Incorporating fusion guided biopsy in active surveillance nearly doubled our detection of pathological progression compared to systematic 12-core biopsy., (Copyright © 2017 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Background: The high-spatial resolution of multiparametric magnetic resonance imaging (mpMRI) has improved the detection of clinically significant prostate cancer. mpMRI characteristics (extraprostatic extension [EPE], number of lesions, etc.) may predict final pathological findings (positive lymph node [pLN] and pathological ECE [pECE]) and biochemical recurrence (BCR). Tumor contact length (TCL) on MRI, defined as the length of a lesion in contact with the prostatic capsule, is a novel marker with promising early results. We aimed to evaluate TCL as a predictor of +pathological EPE (+pEPE),+pathological LN (+pLN), and BCR in patients undergoing robotic-assisted laparoscopic radical prostatectomy., Materials and Methods: A review was performed of a prospectively maintained single-institution database of men with prostate cancer who underwent prostate mpMRI followed by robotic-assisted laparoscopic radical prostatectomy without prior therapy from 2007 to 2015. TCL was measured using T2-weighted magnetic resonance images. Logistic and Cox regression analysis were used to assess associations of clinical, imaging, and histopathological variables with pEPE, pLN, and BCR. Receiver operating characteristic curves were used to characterize and compare TCL performance with Partin tables., Results: There were 87/379 (23.0%)+pEPE, 18/384 (4.7%)+pLN, and 33/371 (8.9%) BCR patients. Patients with adverse pathology/oncologic outcomes had longer TCL compared to those without adverse outcomes (+pEPE: 19.8 vs. 10.1mm, P<0.0001,+pLN: 38.0 vs. 11.7mm, P<0.0001, and BCR: 19.2 vs. 11.2mm, P = 0.001). On multivariate analysis, TCL remained a predictor of+pEPE (odds ratio: 1.04, P = 0.001),+pLN (odds ratio: 1.07, P<0.0001), and BCR (hazard ratio: 1.03, P = 0.02). TCL thresholds for predicting+pEPE and+pLN were 12.5 and 19.7mm, respectively. TCL alone was found to have good predictive ability for+pEPE and+PLN (pEPE:TCL AUC : 0.71 vs. Partin AUC : 0.66, P = 0.21; pLN:TCL AUC : 0.77 vs. Partin AUC : 0.88, P = 0.04)., Conclusion: We demonstrate that TCL is an independent predictor of+pEPE, +pLN, and BCR. If validated, this imaging biomarker may facilitate and inform patient counseling and decision-making., (Published by Elsevier Inc.)

Accurate risk stratification of prostate cancer is achieved with a number of existing tools to ensure the identification of at-risk patients, characterization of disease aggressiveness, prediction of cancer burden and extrapolation of treatment outcomes for appropriate management of the disease. Statistical tables and nomograms using classic clinicopathological variables have long been the standard of care. However, the introduction of multiparametric MRI, along with fusion-guided targeted prostate biopsy and novel biomarkers, are being assimilated into clinical practice. The majority of studies to date present the outcomes of each in isolation. The current review offers a critical and objective assessment regarding the integration of multiparametric MRI and fusion-guided prostate biopsy with novel biomarkers and predictive nomograms in contemporary clinical practice., Competing Interests: Financial & competing interests disclosure This research was supported by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research and the Center for Interventional Oncology. NIH and Philips Healthcare have a cooperative research and development agreement. NIH and Philips share intellectual property in the field. This research was also made possible through the National Institutes of Health Medical Research Scholars Program, a public-private partnership supported jointly by the NIH and generous contributions to the Foundation for the NIH from Pfizer Inc., The Doris Duke Charitable Foundation, The Alexandria Real Estate Equities, Inc. and Mr and Mrs Joel S Marcus and the Howard Hughes Medical Institute, as well as other private donors. For a complete list, please visit the Foundation website at: http://fnih.org/work/education-training-0/medical-research-scholars-program. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.

Purpose: MRI-TRUS fusion biopsy (FBx) has proven efficacy in targeting suspicious areas that are traditionally missed by systematic 12-core biopsy (SBx). Midline prostate lesions are undersampled during SBx, as traditional approaches aim laterally during TRUS biopsy. The aim of our study was to determine the utility of FBx for targeting midline lesions identified on multiparametric MRI (mpMRI)., Methods: A review was performed of a prospectively maintained database of patients undergoing mpMRI followed by FBx and SBx from 2007 to 2015. Midline location was defined as any lesion crossing the midline on axial imaging and involving both prostatic lobes. Index lesion was defined as lesion with highest Gleason score on biopsy. Patient demographic, imaging, and histopathologic data were collected. Multivariate logistic regression was conducted to determine independent predictors of having clinically significant (CS) cancer (Gleason ≥ 7) in midline lesions., Results: Out of 1266 patients, we identified 202 suspicious midline lesions in 190 patients [median (IQR) age 63 (10) years; PSA 7.6 (6.6)]. Eighty-eight (46.3 %) patients had cancer detection on FBx of midline lesion. A midline target represented the index lesion of the prostate in 63/190 (33.2 %) patients. Risk category upgrading based on FBx of a midline lesion compared to SBx occurred in 45/190 patients (23.7 %). On multivariate analysis, higher PSA (p = .001), lower MRI-derived prostate volume (p < .001), and moderate-high or high suspicion on mpMRI (p = .014) predicted CS cancer in midline lesions., Conclusions: MRI-TRUS FBx facilitates sampling of midline lesions. Integration of mpMRI and FBx for targeting of midline lesions improves detection of CS prostate cancer.

Purpose: Urologists face a dilemma when a lesion identified on multiparametric magnetic resonance imaging is benign on image guided fusion biopsy. We investigated the detection rate of prostate cancer on repeat fusion biopsy in multiparametric magnetic resonance imaging lesions initially found to be pathologically benign on fusion biopsy., Materials and Methods: We reviewed the records of all patients from 2007 to 2014 who underwent multiparametric magnetic resonance imaging and image guided fusion biopsy. We identified men who underwent rebiopsy of the same discrete lesion after initial fusion biopsy results were benign. Data were documented on a per lesion basis. We manually reviewed UroNav system (Invivo, Gainesville, Florida) needle tracking to verify accurate image registration. Multivariate analysis was used to identify clinical and imaging factors predictive of prostate cancer detection at repeat fusion biopsy., Results: A total of 131 unique lesions were rebiopsied in 90 patients. Of these 131 resampled lesions 21 (16%) showed prostate cancer, which in 13 (61.9%) was Gleason 3 + 3. On multivariate analysis only lesion growth on repeat multiparametric magnetic resonance imaging was significantly associated with prostate cancer detection at repeat biopsy (HR 3.274, 95% CI 1.205-8.896, p = 0.02)., Conclusions: Pathologically benign multiparametric magnetic resonance imaging lesions on initial image guided fusion biopsy are rarely found to harbor clinically significant prostate cancer on repeat biopsy. When prostate cancer was identified, most disease was low risk. An increase in lesion diameter was an independent predictor of prostate cancer detection. While these data are retrospective, they may provide some confidence in the reliability of negative initial image guided fusion biopsies despite a positive multiparametric magnetic resonance imaging finding., (Copyright © 2016 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Purpose: As the adoption of magnetic resonance imaging/ultrasound fusion guided biopsy expands, the reproducibility of outcomes at expert centers becomes essential. We sought to validate the comprehensive NCI (National Cancer Institute) experience with multiparametric magnetic resonance imaging and fusion guided biopsy in an external, independent, matched cohort of patients., Materials and Methods: We compared 620 patients enrolled in a prospective trial comparing systematic biopsy to fusion guided biopsy at NCI to 310 who underwent a similar procedure at Long Island Jewish Medical Center. The propensity score, defined as the probability of being treated outside NCI, was calculated using the estimated logistic regression model. Patients from the hospital were matched 1:1 for age, prostate specific antigen, magnetic resonance imaging suspicion score and prior negative biopsies. Clinically significant disease was defined as Gleason 3 + 4 or greater., Results: Before matching we found differences between the cohorts in age, magnetic resonance imaging suspicion score (each p <0.001), the number of patients with prior negative biopsies (p = 0.01), and the overall cancer detection rate and the cancer detection rate by fusion guided biopsy (each p <0.001). No difference was found in the rates of upgrading by fusion guided biopsy (p = 0.28) or upgrading to clinically significant disease (p = 0.95). A statistically significant difference remained in the overall cancer detection rate and the rate by fusion guided biopsy after matching. On subgroup analysis we found a difference in the overall cancer detection rate and the rate by fusion guided biopsy (p <0.001 and 0.003) in patients with prior negative systematic biopsy but no difference in the 2 rates (p = 0.39 and 0.51, respectively) in biopsy naïve patients., Conclusions: Improved detection of clinically significant cancer by magnetic resonance imaging and fusion guided biopsy is reproducible by an experienced multidisciplinary team consisting of dedicated radiologists and urologists., (Copyright © 2016 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Introduction: African-American (AA) men tend to harbor high-risk prostate cancer (PCa) and exhibit worse outcomes when compared to other groups. It has been postulated that AA men may harbor more anterior prostate lesions (APLs) that are undersampled by the standard transrectal ultrasound guided-biopsy (SBx), potentially resulting in greater degree of Gleason score (GS) upgrading at radical prostatectomy. We aimed to evaluate the detection rate of anterior PCa significance of APLs in AA men on multiparametric magnetic resonance imaging (mpMRI) and compare it to a matched cohort of White/Other (W/O) men., Materials and Methods: A review of 1,267 men who had an mpMRI with suspicious prostate lesions and who underwent magnetic resonance transrectal ultrasound fusion-guided biopsy (FBx) with concurrent SBx in the same biopsy session was performed. All AA men were matched to a control group of W/O using a 1:1 propensity score-matching algorithm with age, prostate-specific antigen, and prostate volume as matching variables. Logistic regression analysis was used to determine predictors of APLs in AA men., Results: Of the 195 AA men who underwent mpMRI, 93 (47.7%) men had a total of 109 APLs. Prior negative SBx was associated with the presence of APLs in AA men (Odds ratio = 1.81; 95% CI: 1.03-3.20; P = 0.04). On multivariate logistic regression analysis, smaller prostate (P = 0.001) and rising prostate-specific antigen (P = 0.007) were independent predictors of cancer-positive APLs in AA men. Comparative analysis of AA (93/195, 47.7%) vs. W/O (100/194, 52%) showed no difference in the rates of APLs (P = 0.44) or in cancer detection rate within those lesions or the distribution of GS within those cancers (P = 0.63) despite an overall higher cancer detection rate in AA men (AA: 124/195 [63.6%] vs. W/O: 97/194 [50.0%], P = 0.007). In cases where APLs were positive for PCa on FBx, the GS of APL was equal to the highest GS of the entire gland in 82.9% (29/35) and 90.9% (30/33) of the time in AA and W/O men, respectively., Conclusion: Cancer-positive APLs represented the highest risk GS in most cases. AA men with prior negative SBx are twice as likely to harbor a concerning APL. In our cohort, AA and W/O men had comparable rates of APLs on mpMRI. Thus, differences in APLs do not explain the higher risk of AA men for deahth due to PCa. However, targeting of APLs via FBx can clinically improve PCa risk stratification and guide appropriate treatment options., (Copyright © 2016. Published by Elsevier Inc.)

The diagnosis and treatment of prostate cancer continue to evolve with advances in science and technology. The utilization of multiparametric MRI (mp-MRI) to identify lesions in the prostate has given clinicians the ability to visualize malignancy in the prostate with greater confidence. With this new ability came the advancement of fusion biopsy platforms, which allow for direct targeting of these lesions. As with any new technology in medicine, the proper use of these modalities and how they fit into current clinical practice need to be addressed. This review summarizes the current knowledge on how to best optimize which men undergo mp-MRI and fusion biopsies both in the screening and treatment settings.

Purpose: The urology work force is contracting at a time when service demand is increasing due to demographic changes, especially in rural areas. We investigated the impact of rural status and urologist density on kidney and renal pelvis, bladder and prostate cancer mortality at the county level in Illinois., Materials and Methods: We stratified the 102 Illinois counties by 2003 RUCCs as urban (36, RUCCs 1 to 3) and rural (66, RUCCs 4 to 9). Area Health Resource Files were used for county demographic data and urologist density. County level age adjusted mortality rates from 1990 to 2010 were derived from National Center for Health Statistics data using SEER*Stat. We examined the associations of urological cancer mortality rates with rural status and urologist density., Results: Average urologist density significantly differed between rural and urban counties (1.9 vs 3.4/100,000 population, p < 0.01). The kidney and renal pelvis cancer mortality rate in rural counties was higher than in urban counties while that of prostate cancer was lower (4.9 vs 4.3 and 28.7 vs 32.2/100,000 population, respectively, each p < 0.01). Urologist density correlated with the mortality rate of kidney and renal pelvis cancer (Pearson coefficient -0.33, p < 0.01) but not with the bladder or prostate cancer mortality rate. Multiple regression analysis revealed that rurality and lower urologist density (p = 0.01 and < 0.05) were significantly associated with higher kidney and renal pelvis cancer mortality., Conclusions: Rural residence and low urologist density were associated with increased kidney and renal pelvis cancer mortality on the county level in Illinois. Further expansion and testing of evidence-based telemedicine is warranted because remote technical consultation is now technologically feasible, effective, inexpensive and satisfactory to patients., (Copyright © 2015 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Purpose: The human eye is a highly radiosensitive portion of the body and repeat radiation exposure can lead to cataract. The minimum fractionated long-term dose to initiate cataract formation is about 2,500 mSv. We determined whether further radiation related precautions are necessary to protect the eyes of the surgeon., Materials and Methods: Radiation doses received near the right eye of the operating surgeon were measured with a thermoluminescent dosimeter badge worn near the eye of 6 urologists for a single endourological procedure at an academic center. Procedures included stent insertion, ureteroscopic lithotripsy and percutaneous nephrolithotomy. The mean radiation dose was calculated. Extrapolated doses required to potentiate cataract formation were also calculated., Results: We assessed 28 urological procedures for radiation exposure, of which 13 were ureteroscopy done for calculus disease (range 0.05 to 0.66 mSv) and 7 were ureteral stent insertion (range 0.13 to 0.32 mSv). The mean radiation dose received during these cases was 0.208 mSv. Based on the mean dose and an average of 20 such cases per month, it would take about 50 years to reach the minimum threshold for progressive cataract formation. Eight percutaneous renal operations were performed and the mean dose received was 0.125 mSv (range 0.04 to 0.22). Based on 10 cases per month, this would require more than 160 years of exposure to reach the minimal threshold., Conclusions: Long-term radiation can lead to cataract formation. However, the accumulated lifetime exposure of the typical urologist may not necessitate further safety precautions, such as lead-lined glasses., (Copyright © 2013 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Vaccines encoding xenoantigens, "non-self" proteins that are highly homologous to their autologous counterparts, have been investigated as a means to increase immunogenicity and overcome tolerance to "self" antigens. We have previously shown that DNA vaccines encoding native prostatic acid phosphatase (PAP) were able to elicit PAP-specific T cells in both rats and humans, but required multiple immunization courses. In this study, we investigated in a preclinical model whether immunizations with a DNA vaccine encoding a xenoantigen could elicit a cross-reactive immune response to the native protein, potentially requiring fewer immunizations. Lewis rats were immunized with a DNA vaccine encoding human PAP and splenocytes from immunized rats were screened with a human peptide library containing overlapping, 15-mer PAP-derived peptides using T-cell proliferation and interferon γ (IFNγ) release as measures of the immune response. One dominant PAP-specific, RT1.A(l)-restricted, epitope was identified. Direct immunization with the immunodominant peptide (HP(201-215)) containing this epitope demonstrated that it included a naturally presented MHC Class I epitope recognized by CD8(+) T cells in Lewis rats. However, no cross-reactive immune response was elicited to the corresponding rat peptide despite a difference of only three amino acids. Immunization with DNA vaccines encoding rat PAP (rPAP) in which this foreign dominant epitope was included as well as with DNA vaccines coding for a variant of the xenoantigen from which this epitope was deleted, did not elicit responses to the native antigen. Overall, these results indicate that the immunization with a xenoantigen-coding DNA vaccine can lead to an immune response which potentially favors foreign epitopes and hence limits any cross-reactive response to the native antigen.

Prostatic acid phosphatase (PAP) has been investigated as the target of several antigen-specific anti-prostate tumor vaccines. The goal of antigen-specific active immunotherapies targeting PAP would ideally be to elicit PAP-specific CD8+ effector T cells. The identification of PAP-specific CD8+ T-cell epitopes should provide a means of monitoring the immunological efficacy of vaccines targeting PAP, and these epitopes might themselves be developed as vaccine antigens. In the current report, we hypothesized that PAP-specific epitopes might be identified by direct identification of pre-existing CD8+ T cells specific for HLA-A2-restricted peptides derived from PAP in the blood of HLA-A2-expressing individuals. 11 nonamer peptides derived from the amino acid sequence of PAP were used as stimulator antigens in functional ELISPOT assays with peripheral blood mononuclear cells from 20 HLA-A2+ patients with prostate cancer or ten healthy blood donors. Peptide-specific T cells were frequently identified in both groups for three of the peptides, p18-26, p112-120, and p135-143. CD8+ T-cell clones specific for three peptides, p18-26, p112-120, and p299-307, confirmed that these are HLA-A2-restricted T-cell epitopes. Moreover, HLA-A2 transgenic mice immunized with a DNA vaccine encoding PAP developed epitope-specific responses for one or more of these three peptide epitopes. We propose that this method to first identify epitopes for which there are pre-existing epitope-specific T cells could be used to prioritize MHC class I-specific epitopes for other antigens. In addition, we propose that the epitopes identified here could be used to monitor immune responses in HLA-A2+ patients receiving vaccines targeting PAP to identify potentially therapeutic immune responses.

Prostatic acid phosphatase (PAP) is a prostate cancer tumor antigen and a prostate-specific protein shared by rats and humans. Previous studies indicated that Copenhagen rats immunized with a recombinant vaccinia virus expressing human PAP (hPAP) developed PAP-specific cytotoxic T cells (CTL) with cross reactivity to rat PAP (rPAP) and evidence of prostate inflammation. Viral delivery of vaccine antigens is an active area of clinical investigation. However, a potential difficulty with viral-based immunizations is that immune responses elicited to the viral vector might limit the possibility of multiple immunizations. In this paper, we investigate the ability of another genetic immunization method, a DNA vaccine encoding PAP, to elicit antigen-specific CD8+ T cell immune responses. Specifically, Lewis rats were immunized with either a plasmid DNA-based (pTVG-HP) or vaccinia-based (VV-HP) vaccine each encoding hPAP. We determined that rats immunized with a DNA vaccine encoding hPAP developed a Th1-biased immune response as indicated by proliferating PAP-specific CD4+ and CD8+ cells and IFNgamma production. Rats immunized with vaccinia virus encoding PAP did not develop a PAP-specific response unless boosted with a heterologous vaccination scheme. Most importantly, multiple immunizations with a DNA vaccine encoding the rat PAP homologue (pTVG-RP) could overcome peripheral self-tolerance against rPAP and generate a Th1-biased antigen-specific CD4+ and CD8+ T cell response. Overall, DNA vaccines provide a safe and effective method of generating prostate antigen-specific T cell responses. These findings support the investigation of PAP-specific DNA vaccines in human clinical trials.

Prostatic acid phosphatase (PAP) is a prostate tumor antigen currently being investigated as a target antigen in several human vaccine trials, some with evidence of clinical benefit. We have previously demonstrated that plasmid DNA vaccines encoding either human or rat PAP can elicit antigen-specific cellular and humoral immunity in rat models. The current study was performed to determine the safety and potential immunological efficacy in rodents of large and repetitive doses of a GMP-grade plasmid DNA vaccine encoding human PAP, pTVG-HP. Fifty-four male Lewis rats were immunized intradermally at 2-week intervals with 100, 500, or 1,500 microg pTVG-HP with 5 microg recombinant rat GM-CSF protein given as a vaccine adjuvant. An additional 12 male Lewis rats served as controls with groups immunized with 1,500 microg of a parental DNA vector not encoding human PAP, and a group that received GM-CSF protein only without plasmid DNA. Groups of animals (n=3-6) were euthanized after two, four, or six immunizations with collections of tissues and blood for toxicity assessment and immunological analysis. No significant toxicities were observed in terms of animal weights, histopathology, hematological changes, or changes in serum chemistries. Six of fifty-four were found to have subtle evidence of possible renal toxicity, however these findings were not statistically different from control animals. The vaccine was found to be effective in eliciting PAP-specific CD4 and CD8 T cells, predominantly Th1 in type, in all immunized animals at all doses and numbers of immunizations. PAP-specific IgG were detected in a dose-dependent fashion, with titers increasing after multiple immunizations. These studies demonstrate that, in rats, immunization with the pTVG-HP vaccine is safe and effective in eliciting PAP-specific cellular and humoral immune responses. These findings support the further clinical evaluation of pTVG-HP in patients with prostate cancer.