The human gastrointestinal microbiota and prostate cancer development and treatment.

The human gastrointestinal microbiome contains commensal bacteria and other microbiota that have been gaining increasing attention in the context of cancer development and response to treatment. Microbiota play a role in the maintenance of host barrier surfaces that contribute to both local inflammation and other systemic metabolic functions. In the context of prostate cancer, the gastrointestinal microbiome may play a role through metabolism of estrogen, an increase of which has been linked to the induction of prostatic neoplasia. Specific microbiota such as Bacteroides, Streptococcus, Bacteroides massiliensis, Faecalibacterium prausnitzii, Eubacterium rectalie, and Mycoplasma genitalium have been associated with differing risks of prostate cancer development or extensiveness of prostate cancer disease. In this Review, we discuss gastrointestinal microbiota's effects on prostate cancer development, the ability of the microbiome to regulate chemotherapy for prostate cancer treatment, and the importance of using Next Generation Sequencing to further discern the microbiome's systemic influence on prostate cancer.

Antibiotic resistance, hospitalizations, and mortality related to prostate biopsy: first report from the Norwegian Patient Registry.

BACKGROUND: A 68-year-old man died of cerebral arterial embolism 6 days after transrectal prostate biopsy with a single p.o. dose of trimethoprim sulfamethoxazole (TMP-SMX) as prophylaxis. The case precipitated analysis of local antibiotic resistance and complication rates. MATERIALS AND METHODS: Data on E. coli resistance from Oslo University Hospital and national data on hospitalizations and mortality after biopsy were retrieved from local microbiology files and the Norwegian Patient Registry (NPR) 2011-2017. RESULTS: Urine E. coli resistance against TMP-SMX increased from 35% in 2013 to more than 60% in 2015. For ciprofloxacin, the resistance increased from 15% in 2013 to about 45% in 2016. The highest annual E. coli resistance in blood cultures for TMP-SMX and ciprofloxacin was 37% and 28%, respectively. 10% of patients were hospitalized with a diagnosis of infection within the first 60 days after biopsy and there was a relative increase in mortality rate of 261% within the first 30 days. Due to the severity of the figures, the story and the NPR data were published in Norway's leading newspaper and were succeeded by a series of chronicles and commentaries. CONCLUSIONS: Several critical points of the biopsy procedure were not performed according to current standards. We believe that the patient might have died of septic embolism after biopsy. As a result of the findings and the debate, local practice was changed from transrectal to transperineal prostate biopsies.

Metagenomics in diagnosis and improved targeted treatment of UTI.

INTRODUCTION: The genomic revolution has transformed our understanding of urinary tract infection. There has been a paradigm shift from the dogmatic statement that urine is sterile in healthy people, as we are becoming forever more familiar with the knowledge that bacterial communities exist within the urinary tracts of healthy people. Metagenomics can investigate the broad populations of microbial communities, analysing all the DNA present within a sample, providing comprehensive data regarding the state of the microenvironment of a patient's urinary tract. This permits medical practitioners to more accurately target organisms that may be responsible for disease-a form of 'precision medicine'. METHODS AND RESULTS: This paper is derived from an extensive review and analysis of the available literature on the topic of metagenomic sequencing in urological science, using the PubMed search engine. The search yielded a total of 406 results, and manual selection of appropriate papers was subsequently performed. Only one randomised clinical trial comparing metagenomic sequencing to standard culture and sensitivity in the arena of urinary tract infection was found. CONCLUSION: Out of this process, this paper explores the limitations of traditional methods of culture and sensitivity and delves into the recent studies involving new high-throughput genomic technologies in urological basic and clinical research, demonstrating the advances made in the urinary microbiome in its entire spectrum of pathogens and the first attempts of clinical implementation in several areas of urology. Finally, this paper discusses the challenges that must be overcome for such technology to become widely used in clinical practice.

Clinical Proof-of-concept of a Novel Platform Utilizing Biopsy-derived Live Single Cells, Phenotypic Biomarkers, and Machine Learning Toward a Precision Risk Stratification Test for Prostate Cancer Grade Groups 1 and 2 (Gleason 3 + 3 and 3 + 4).

OBJECTIVE: To examine the ability of a novel live primary-cell phenotypic (LPCP) test to predict postsurgical adverse pathology (P-SAP) features and risk stratify patients based on SAP features in a blinded study utilizing radical prostatectomy (RP) surgical specimens. METHODS: Two hundred fifty-one men undergoing RP were enrolled in a prospective, multicenter (10), and proof-of-concept study in the United States. Fresh prostate samples were taken from known areas of cancer in the operating room immediately after RP. Samples were shipped and tested at a central laboratory. Utilizing the LPCP test, a suite of phenotypic biomarkers was analyzed and quantified using objective machine vision software. Biomarkers were objectively ranked via machine learning-derived statistical algorithms (MLDSA) to predict postsurgical adverse pathological features. Sensitivity and specificity were determined by comparing blinded predictions and unblinded RP surgical pathology reports, training MLDSAs on 70% of biopsy cells and testing MLDSAs on the remaining 30% of biopsy cells across the tested patient population. RESULTS: The LPCP test predicted adverse pathologies post-RP with area under the curve (AUC) via receiver operating characteristics analysis of greater than 0.80 and distinguished between Prostate Cancer Grade Groups 1, 2, and 3/Gleason Scores 3 + 3, 3 + 4, and 4 + 3. Further, LPCP derived-biomarker scores predicted Gleason pattern, stage, and adverse pathology with high precision-AUCs>0.80. CONCLUSION: Using MLDSA-derived phenotypic biomarker scores, the LPCP test successfully risk stratified Prostate Cancer Grade Groups 1, 2, and 3 (Gleason 3 + 3 and 7) into distinct subgroups predicted to have surgical adverse pathologies or not with high performance (>0.85 AUC).

Transrectal Ultrasound-guided Versus Transperineal Mapping Prostate Biopsy: Complication Comparison.

Herein, the authors compare morbidity in men who underwent both transrectal ultrasound-guided (TRUS) prostate biopsy and transperineal mapping biopsy (TPMB) at two institutions with extensive experience in both procedures. We also identified strategies and predictive factors to reduce morbidity for both procedures. In our study, 379 men from two institutions, of which 265 (69.9%) had a prior TRUS-guided biopsy, also had TPMB performed via a template with biopsies taken at 5-mm intervals. Men in the TRUS group had a median of 12 cores sampled whereas the TPMB group had 51.5 (range, 16-151). The median biopsy density was 1.1 core/cc prostate volume. Median age and prostate-specific antigen (PSA) level were 65 years (range, 34-86) and 5.5 ng/mL (range, 0.02-118). Of these men, 11 of 265 (4.2%) who had TRUS biopsy developed urinary tract infection compared with 3 of 379 (0.79%) of those with mapping biopsy. Infection was 14.8% in TRUS biopsy group with 13 or more cores versus 2.9% in those with 12 or less (OR, 5.8; 95% CI, 1.6-21.2; P = 0.003). No men developed retention after TRUS biopsy whereas 30 of 379 (7.9%) did following TPMB. Older age, larger prostate volume (PV), and higher core number were associated with retention. On linear regression only age (P = 0.010) and PV (P = 0.016) remained as significant associations. Men older than 65 years had 12.8% versus 3.9% (OR, 3.7; 95% CI, 1.6-8.4, P = 0.001) and PV greater than 42 cc had 13.4% versus 2.7% (OR, 5.7; 95% CI, 2.1-15.1) retention incidence. In the present study TPMB is rarely associated with infection (0.78%) but more commonly with urinary retention (7.9%). Men older than 65 years and with PV greater than 42 cc were at four to five times greater retention risk. Consideration should be given to discharging these men with a urinary catheter following TPMB.

An implementation of next generation sequencing for prevention and diagnosis of urinary tract infection in urology.

INTRODUCTION: The changing face of current infection phenotypes from planktonic to biofilm type has been developed implicating bacterial biofilms in recurrent infection. To date, no specific medical treatment exists to specifically target biofilms in the human host. Similarly, the identification of a biofilm has relied upon the analysis of tissue samples with electron microscopy or DNA identification with polymerase chain reaction (PCR) and sequencing. Standard culture and sensitivity test is not able to detect a presence of biofilms. MATERIALS AND METHODS: Two types of molecular microbial diagnostic testing 'levels' are performed as noted below. In both types of analysis, the microbial DNA is extracted from the patient's sample. The patient report contains information about the pathogenic bacterial and fungal microorganisms detected, bacterial load and resistance genes to different antibiotics. Once the bacteria have been identified antibiotic recommendations are made based on research confirming the effectiveness of treatment. The technique was tested in 112 patients in different areas of urology for prevention and treatment purpose. RESULTS: The clinical application of next generation sequence in different clinical phase I-II trials (acute cystitis in 56 patients, rectal swabs before transrectal prostate biopsy in 32 men, neurogenic bladder in 13 patients, chronic bacterial prostatitis in 17 men) demonstrated that this novel approach extends our knowledge about the microbiome of the urogenital tract in both men and women. DNA sequence has a high sensitivity to detect a bacterial and fungal association with resistant genes to antibiotics revealed allowing to implement a targeted and individual prevention and treatment of urinary tract infection (UTI) with improved efficacy compared to standard culture and sensitivity technique. CONCLUSION: The next generation DNA sequence technology enables the discovery of new concepts regarding the role of microorganisms in diseases of the urinary tract with an individualized approach for a more accurate diagnosis, prevention, prophylaxis and treatment of UTI.

The 3DBiopsy Prostate Biopsy System: Preclinical Investigation of a Needle, Actuator, and Specimen Collection Device Allowing Sampling of Individualized Prostate Lengths Between 20 and 60 mm.

OBJECTIVE: To increase the likelihood of detecting anterior cancers within the prostate and provide a specimen that spans the length of the gland. Newly designed 17- and 15-gauge (G) biopsy needles, a variable actuator, and an integrated pathology system intended for the longer cores were developed and tested for this purpose. MATERIALS AND METHODS: Testing was performed comparing 2 common cannula tip grinds, a Vet-point (sharp tip) and a Menghini-point (atraumatic tip), and were tested against 18-G Bard Monopty in porcine kidney. A variable actuator was developed to fire the needle 20-60 mm and tested in cadaver prostates. RESULTS: The aggregate firings for 3 different shot lengths comparing the Vet- with the Menghini-tip cannulas demonstrated 91% vs 85.2% fill (length of specimen/length of core bed, P = .007). A 15-G trocar needle with the Vet-tip cannula also had the best performance, with an aggregate standard deviation of 6.4% across 3 firing ranges and a minimum to maximum specimen length of 81%-105% of potential fill. Cadaver testing with the Vet-tip needles in the actuator for the transrectal (17-G) and transperineal (15-G) biopsies demonstrated mean fills of 93.3% and 76.5%, respectively. The new transrectal ultrasound needle obtained a 2-fold increase in specimen length over the standard Bard device (P <.001). CONCLUSION: Longer and consistent cores were obtained using the new biopsy needles. Combined with an adjustable actuator, the physician can obtain specimens that include peripheral and anterior zone tissue in 1 core. Determination of cancer location on the longer specimens could enhance focal therapy planning.

Prostate Specific Antigen Nadir of 0.1 or Less Is a Predictor of Treatment Success in Men Undergoing Salvage Whole Prostate Gland Cryoablation.

PURPOSE: To assess factors that affect prostate biopsy results following salvage whole gland cryoablation. PATIENTS AND METHODS: One hundred seventy-four patients underwent prostate biopsy following salvage whole gland cryoablation of the prostate in the Cryo-OnLine Database registry. Wilcoxon rank-sum and χ2 tests and logistic regression analysis were used to assess predictors of positive biopsy. Prostate specific antigen (PSA) nadir was divided into a statistical tertile for comparisons between different nadir PSA cut points. RESULTS: Fifty-two of 174 (29.9%) of this highly select group of men who underwent biopsy had a posttreatment biopsy demonstrating malignant cancer. Men who had positive biopsy following salvage therapy had significantly higher median nadir PSA, shorter median time to prostate biopsy, and shorter median time to biochemical failure. Compared to the lowest tertile (PSA nadir defined as ≤0.1 ng/mL), PSA in the second tertile (0.11-0.8 ng/mL) and third tertile (>0.8 ng/mL) demonstrated increased odds ratio (OR) for positive biopsy, 4.34 (95% confidence interval [CI] 1.66, 11.4, p = 0.003) and 2.81 (95% CI 1.14, 7.00, p = 0.02), respectively, in adjusted models. In addition, men with a presalvage PSA >20 (OR 7.65; 95% CI 2.03, 28.9; p = 0.003) and Gleason score ≥8 (OR 2.26; 95% CI 0.93, 5.47; p = 0.07) had a higher OR of positive biopsy. CONCLUSIONS: Nadir PSA of 0.1 ng/mL or less following salvage cryotherapy is predictive of treatment success. Routine biopsy should be reserved for men with nadir PSA >0.1 ng/mL and patients with high risk features of prostate cancer before salvage cryoablation.

Rapid and Short-term Extracellular Matrix-mediated In Vitro Culturing of Tumor and Nontumor Human Primary Prostate Cells From Fresh Radical Prostatectomy Tissue.

OBJECTIVE: To culture prostate cells from fresh biopsy core samples from radical prostatectomy (RP) tissue. Further, given the genetic heterogeneity of prostate cells, the ability to culture single cells from primary prostate tissue may be of importance toward enabling single-cell characterization of primary prostate tissue via molecular and cellular phenotypic biomarkers. METHODS: A total of 260 consecutive tissue samples from RPs were collected between October 2014 and January 2016, transported at 4°C in serum-free media to an off-site central laboratory, dissociated, and cultured. A culture protocol, including a proprietary extracellular matrix formulation (ECMf), was developed that supports rapid and short-term single-cell culture of primary human prostate cells derived from fresh RP samples. RESULTS: A total of 251 samples, derived from RP samples, yielded primary human tumor and nontumor prostate cells. Cultured cells on ECMf exhibit (1) survival after transport from the operating room to the off-site centralized laboratory, (2) robust (>80%) adhesion and survival, and (3) expression of different cell-type-specific markers. Cells derived from samples of increasing Gleason score exhibited a greater number of focal adhesions and more focal adhesion activation as measured by phospho-focal adhesion kinase (Y397) immunofluorescence when patient-derived cells were cultured on ECMf. Increased Ki67 immunofluorescence levels were observed in cells derived from cancerous RP tissue when compared to noncancerous RP tissue. CONCLUSION: By utilizing a unique and defined extracellular matrix protein formulation, tumor and nontumor cells derived from primary human prostate tissue can be rapidly cultured and analyzed within 72 hours after harvesting from RP tissue.

A Head-to-Head Comparative Phase II Study of Standard Urine Culture and Sensitivity Versus DNA Next-generation Sequencing Testing for Urinary Tract Infections.

Many studies have discussed clinical practice guidelines for the treatment of cystitis and pyelonephritis. Treatment of uncomplicated urinary tract infections (UTIs) can be based on empiric antibiotic therapy. For complicated or recurrent UTIs, therapy can be based on laboratory-controlled culture and sensitivity (C&S) reports. The diagnosis of UTI by clinical criteria alone has an error rate of up to 33%. In addition, positive laboratory culture results do not always indicate a diagnosis of UTI. Comparison of urine in a conventional culture model versus DNA next-generation sequencing (NGS) to accurately identify and provide information on resistance factors (mobile genetic elements) is warranted. Our study was a head-to-head comparative phase II study of standard urine C&S versus DNA NGS testing for the diagnosis and treatment efficacy in patients with symptoms of acute cystitis based on short-term outcomes.

Diffusion of Robotic Technology Into Urologic Practice has Led to Improved Resident Physician Robotic Skills.

OBJECTIVE: To investigate whether propagation of robotic technology into urologic practice and training programs has improved baseline urology resident trainee robotic skills. DESIGN: Questionnaires were completed by each urology resident trainee participating in a training course and asked about access to robotic simulation, robot experience, and console time. Baseline resident trainee scores on the Mimic Robotic Simulator (Mimic Technologies, Inc., Seattle, WA) from 27 participants of 2012 course were compared with the 2015 scores of 34 trainees on 4 standard Mimic exercises using Wilcoxon rank-sum tests. p = 0.05 or less were considered statistically significant. PARTICIPANTS AND SETTING: Totally, 34 resident trainees from 17 programs in the Southeast Section of the American Urological Association participated in an annual 2-day robotic training course. RESULTS: Overall score, economy of motion score, and time to complete exercise were all significantly better in the 2015 trainee group compared with the 2012 trainee group (p < 0.001) for the Peg Board 1, Camera Targeting 2, and Energy Dissection exercises. Overall scores for needle targeting improved between 2012 and 2015 (p = 0.04). Trainee access to a simulator was not associated with overall score on any of the 4 exercises in the 2015 group. In the 2015 group, actual robotic console time was associated with better overall scores in Camera Targeting 2 (p = 0.02) and Peg Board 1 (p = 0.04). CONCLUSIONS: Baseline resident trainee performance on basic robotic simulator exercises has improved over the past 3 years irrespective of robotic simulator access or console time.

Safety of selective nerve sparing in high risk prostate cancer during robot-assisted radical prostatectomy.

D'Amico high risk prostate cancer is associated with higher incidence of extra prostatic disease. It is recommended to avoid nerve sparing in high risk patients to avoid residual cancer. We report our intermediate term oncologic and functional outcomes in patients with preoperative D'Amico high risk prostate cancer, who underwent selective nerve sparing robot-assisted radical prostatectomy (RARP). Between Jan 2008 till June 2013, 557 patients underwent RARP for D'Amico high risk prostate cancer. The criteria for nerve sparing were as follows-complete: non palpable disease with <3 cores involvement on prostate biopsy; partial: non palpable disease with <4 cores involvement on prostate biopsy; none: clinically palpable disease with ≥4 cores involvement on prostate biopsy and intraoperative visual cues of locally advanced disease (loss of dissection planes, focal bulge of prostatic capsule). Degree of nerve sparing (NS) was graded intraoperatively by the surgeon independently at either side as side specific margins were assessed to predict subjectivity of the intraoperative judgment. Various data were collected and analyzed. Of 557 patients who underwent RARP 140 underwent complete (group 1), 358 patients underwent partial (group 2), and 59 patients underwent non-nerve-sparing procedure (group 3). There were no difference in preoperative characteristic between the groups (p = 0.678), but group 3 had higher Gleason score sum (p = 0.001), positive cores on biopsy (p = 0.001) and higher t stage (p = 0.001). Postoperatively Extra prostatic extension (p = 0.001), seminal vesicle invasion (p = 0.001), and tumor volume (p < 0.001) were higher in Group 3. Side specific positive surgical margins (PSMs) rates were higher for non-nerve-sparing compared to partial and complete nerve sparing RARP (p < 0.001; overall PSMs = 25.2 %). On univariate and multivariate analysis, nerve sparing did not affect PSMs (p > 0.05). The overall biochemical recurrence (BCR) rate at mean follow-up of 24.3 months was 19.21 %. The continence rate at 3 month was significantly higher in complete NS group in comparison to non-NS group (p = 0.020), however, this difference was not statistically significant at 1 year. Similarly, mean time to continence was significantly lower in complete NS group in comparison to non-NS group (p = 0.030). The potency rate was significantly higher and mean time to potency was significantly lower in complete NS group in comparison to non-NS group (p = 0.010 and 0.020, respectively). In high risk prostate cancer patients, selective nerve sparing during RARP, using the preoperative clinical variables (clinical stage and positive cores on biopsy) and surgeon's intraoperative perception, could provide reasonable intermediate term oncologic, functional outcomes (continence and potency) with acceptable perioperative morbidity and positive surgical margins rate. Use of these preoperative factors and surgeon's intraoperative judgment can appropriately evaluate high risk prostate cancer patients for nerve sparing RARP.

Deflection Analysis of Different Needle Designs for Prostate Biopsy and Focal Therapy.

OBJECTIVE: The biopsy needles currently used were designed for a transrectal biopsy and are known to experience significant deflection from the point of entry into the gland to the needle tip. METHODS: Five designs were selected for testing: 18-gauge Bard, 15-gauge lancet tip needle with 12° vet-point cannula, and trocar tip needle with 12°, 15°, and 20° vet-point cannulas. The 15-gauge needle was designed to take a variable specimen sample between 20 and 60 mm, whereas the Bard needle specimen bed was fixed at 20 mm. The needles were bench tested on a spring-loaded platform and fired into gelatin matrix with modulus of elasticity similar to human prostate. RESULTS: The Bard device with lancet tip needle deflected an average of 0.9 mm (range 0.3-1.3 mm) and 1.9° (range 0.6°-2.8°). Increasing needle diameter from 18-gauge Bard to 15-gauge variable with the same lancet tip needle design resulted in an average deflection across the 3 test lengths of 0.9 mm (range 0-2.0 mm) and 0.9° (range 0°-2.0°) with no significant difference. On the contrary, the use of the 3-point trocar tip needles with 12°, 15°, and 20° vet-point cannulas demonstrated significant reduction in the extent of deflection in both millimeters and degrees. There was no deflection at the 2- and 4-cm shots for both spring loads and preloads for the 3 vet tip angles tested. At 6 cm, the 20° vet tip performed the best. CONCLUSION: We proposed a mechanism that provides more accurate prostate sampling by combining a 3-point trocar tip on the needle with a 20° vet tip on the cutting cannula. Using the phantom, mimicking prostate gland tissue density, no deflection was revealed between 20- and 60-mm biopsy lengths, which should permit a straight sample in the majority of prostate glands and improve cancer localization for focal therapy planning.

Predictive factors and oncological outcomes of persistently elevated prostate-specific antigen in patients following robot-assisted radical prostatectomy.

Our aim was to evaluate factors associated with persistently elevated prostate-specific antigen (PSA) and biochemical recurrence following robotic-assisted radical prostatectomy (RARP). The study population (N = 5300) consisted of consecutive patients who underwent RARP for localized prostate cancer by a single surgeon (VP) from January 2008 through July 2013. A query of our Institutional Review Board-approved registry identified 162 men with persistently elevated PSA (group A), defined as PSA level ≥0.1 ng/ml at 6 weeks after surgery, who were compared with rest of the cohort group having undetectable PSA, group B (<0.1 ng/ml). A univariate and multivariate logistic regression analysis was used to evaluate the significant association between various variables and the following: (1) persistently elevated PSA, (2) BCR (PSA value ≥0.2 ng/ml) on follow-up in the persistent PSA group. On multivariate analysis, only the following parameters were significantly associated with persistent PSA after RARP-preoperative [PSA >10 ng/ml (p = 0.01), Gleason Score ≥8 (p = 0.001) and clinical stage(p = 0.001)]; postoperative [pathologic stage (p = 0.001), extraprostatic extension (EPE, p = 0.01), lymph node positivity (p = 0.001), positive surgical margin (PSM, p = 0.02), Gleason score (p = 0.01) and tumor volume percent (p < 0.001)]. The mean follow-up was 38.1 months. The BCR was significantly higher in group A as compared to group B(52.47 vs 7.9 %) respectively; p = 0.01). The mean time to BCR was significantly lesser in group A as compared to group B(8.9 vs 21.1 months respectively; p = 0.01). The BCR-free survival rates at 1 year and 3 years were significantly lower statistically in the persistent PSA group in comparison to other groups (69.7 vs 97.3 % and 48.5 vs 92.1 %, respectively; p = 0.01). On multivariate logistic regression analysis in patients with persistent PSA on follow-up, preoperative PSA >10 ng/ml, postoperative Gleason score ≥8, postoperative stage ≥pT3, positive pelvic lymph nodes, PSM >3 mm and post-RARP PSA doubling time (DT) <10 months (p < 0.001) were significantly associated with BCR. In patients after RARP, factors associated with aggressive disease (high preoperative PSA, Gleason score ≥8, stage ≥T3, PSM, high tumor volume percent and EPE) predict PSA persistence. Although these patients with persistent PSA after RARP are more likely to have BCR and that too earlier than those patients with undetectable PSA after RARP, a significant proportion of these patients (47.53 %) remain free of BCR. This subset of patients is associated with these favorable parameters (preoperative PSA <10 ng/ml, post-RARP PSA DT ≥10 months, postoperative Gleason score <8, pathologic stage 

Current status of various neurovascular bundle-sparing techniques in robot-assisted radical prostatectomy.

Nerve-sparing procedures during robot-assisted radical prostatectomy (RARP) have demonstrated improved postoperative functional outcomes. This article provides an overview of clinically applied prostatic neuro-anatomy, various techniques of nerve sparing (NS), and recent innovations in NS and potency outcomes of NS RARP. We retrieved and reviewed all listed publications within PubMed using keywords: nerve sparing, robotic radical prostatectomy, prostate cancer, outcomes, pelvic neuroanatomy and potency. Studies reporting potency outcomes of NS RARP (comparative and non-comparative) were analysed using the Delphi method with an expert panel of urological robotic surgeons. Herein, we outline the published techniques of NS during RARP. Potency and continence outcomes of individual series are discussed in light of the evidence provided by case series and published trials. The potency outcomes of various comparative and non-comparative series of NS RARP have also been mentioned. There are numerous NS techniques reported for RARP. Each method is complimented with benefits and constrained by idiosyncratic caveats, and thus, careful patient selection, a wise intraoperative clinical judgment and tailored approach for each patient is required, when decision for nerve sparing is made. Further large prospective multi-institutional randomized controlled trials are required to evaluate potency and continence outcomes of these techniques, using a rigid standard patient selection criteria and definition of potency are warranted in the new era of functional outcome-driven research.

Urology residents experience comparable workload profiles when performing live porcine nephrectomies and robotic surgery virtual reality training modules.

In pursuit of improving the quality of residents' education, the Southeastern Section of the American Urological Association (SES AUA) hosts an annual robotic training course for its residents. The workshop involves performing a robotic live porcine nephrectomy as well as virtual reality robotic training modules. The aim of this study was to evaluate workload levels of urology residents when performing a live porcine nephrectomy and the virtual reality robotic surgery training modules employed during this workshop. Twenty-one residents from 14 SES AUA programs participated in 2015. On the first-day residents were taught with didactic lectures by faculty. On the second day, trainees were divided into two groups. Half were asked to perform training modules of the Mimic da Vinci-Trainer (MdVT, Mimic Technologies, Inc., Seattle, WA, USA) for 4 h, while the other half performed nephrectomy procedures on a live porcine model using the da Vinci Si robot (Intuitive Surgical Inc., Sunnyvale, CA, USA). After the first 4 h the groups changed places for another 4-h session. All trainees were asked to complete the NASA-TLX 1-page questionnaire following both the MdVT simulation and live animal model sessions. A significant interface and TLX interaction was observed. The interface by TLX interaction was further analyzed to determine whether the scores of each of the six TLX scales varied across the two interfaces. The means of the TLX scores observed at the two interfaces were similar. The only significant difference was observed for frustration, which was significantly higher at the simulation than the animal model, t (20) = 4.12, p = 0.001. This could be due to trainees' familiarity with live anatomical structures over skill set simulations which remain a real challenge to novice surgeons. Another reason might be that the simulator provides performance metrics for specific performance traits as well as composite scores for entire exercises. Novice trainees experienced substantial mental workload while performing tasks on both the simulator and the live animal model during the robotics course. The NASA-TLX profiles demonstrated that the live animal model and the MdVT were similar in difficulty, as indicated by their comparable workload profiles.

Primary Cryotherapy for High-Grade Clinically Localized Prostate Cancer: Oncologic and Functional Outcomes from the COLD Registry.

OBJECTIVE: To evaluate the oncological and functional outcomes of primary cryotherapy in men with clinically localized, high-grade prostate cancer. SUBJECTS AND METHODS: We included all men with biopsy Gleason score ≥8, localized (cT1-2) disease with a serum prostate-specific antigen (PSA) ≤50 ng/mL from the Cryo On-Line Data (COLD) registry. The primary outcome was biochemical progression free survival (BPFS) as defined by the Phoenix criteria (nadir PSA +2 ng/mL). Secondary outcomes of continence (defined as strictly no leak) and potency (able to have intercourse) were patient reported. Factors influencing BPFS were evaluated individually using Kaplan Meier and in a multivariate model using Cox regression. RESULTS: Altogether, 300 men were included for analysis. The median follow-up was 18.2 months (mean 28.4) and median BPFS was 69.8 months. Based on Kaplan-Meier analysis, the estimated 2- and 5-year BPFS rate was 77.2% and 59.1%, respectively. Neoadjuvant hormonal therapy was administered to 41% of men and this tended to occur in men with larger prostates, likely as a technical consideration for downsizing before cryosurgery. At multivariate analysis, the presence of Gleason score 9 or 10 (Hazard Ratio [HR] 1.9) and a posttreatment PSA nadir of ≥0.4 ng/mL (HR 5.7) were the only significant variables associated with biochemical progression using Cox regression. Complete continence was noted in 90.5% of men and potency in 17% of men at the 12-month follow-up. The incidence of rectourethral fistulae and urinary retention requiring intervention beyond temporary catheterization was 1.3% and 3.3%, respectively. CONCLUSION: Primary cryotherapy appears to be effective and safe in the community setting for high-grade, clinically localized prostate cancer in the short term.

Prevalence and risk factors of contralateral extraprostatic extension in men undergoing radical prostatectomy for unilateral disease at biopsy: A global multi-institutional experience.

INTRODUCTION: We assessed the incidence of contralateral prostate cancer (cPCa), contralateral EPE (cEPE) and contralateral positive surgical margins (cPSM) in patients diagnosed preoperatively with unilateral prostate cancer and evaluated risk factors predictive of contralateral disease extension. METHODS: The occurrence of cPCa, cEPE and cPSM and the side-specific nerve-sparing technique performed were collected postoperatively from 327 men diagnosed with unilateral prostate cancer at biopsy. Parameters, such as the localization, proportion, and percentage of cancer in positive cores, were prospectively collected. RESULTS: Overall, 50.5% of patients had bilateral disease, and were at higher risk when associated with a positive biopsy core at the apex (p = 0.016). The overall incidence of ipsilateral EPE and cEPE were 21.4% and 3.4%, respectively (p < 0.001). Compared to cPCa, ipsilateral disease was at an almost 4-fold higher risk of extending out of the prostate (p < 0.001). None of the criteria tested were identified as useful predictors for cEPE. The low incidence of cEPE in our cohort could limit our ability to detect significance. The overall incidence of ipsilateral PSM and cPSM were 15.3% and 5.8%, respectively (p < 0.001). More aggressive nerve-sparing was not associated with a higher incidence of PSM. Prostate sides selected for more aggressive nerve-sparing were associated with younger patients (p < 0.001), a smaller prostate (p = 0.006), and a lower percentage of cancer in biopsy material (p = 0.008). CONCLUSION: Although the risk of cPCa is high in patients diagnosed with unilateral prostate cancer at biopsy, the risk of cEPE and cPSM is low, yet not insignificant. Contralateral aggressive nerve-sparing should be used with caution and should not compromise oncological outcome.

A pretreatment nomogram for prediction of biochemical failure after primary cryoablation of the prostate.

BACKGROUND: To create a predictive nomogram for biochemical failure following primary whole-gland cryoablation of the prostate for localized prostate cancer (LPCa). METHODS: We retrospectively analyzed 2,242 patients from the Cryo On-Line Database (COLD) who were treatment naive and had undergone primary whole gland cryoablation of the prostate for biopsy-confirmed LPCa. Kaplan-Meier (KM) curves estimating 5 year biochemical progression-free survival (bPFS) were generated. Multivariable Cox proportional hazards analysis (CoxPH) was performed in order to construct the nomogram. The nomogram was internally validated using the bootstrap technique. RESULTS: Overall, the KM estimated 5 year bPFS was 72.8%. Stratified by D'Amico risk, The KM estimated 5 year bPFS was 82.6%, 71.1%, and 57.8% for low-, intermediate-, and high-risk groups, respectively. Statistically significant predictors of biochemical outcomes from CoxPH analysis were pre-treatment prostate specific antigen (PTPSA) (P < 0.001), total prostate volume (P = 0.004), clinical stage (P = 0.034), and Gleason score (0.004). A nomogram for predicted 5 year biochemical progression free probability was constructed with a concordance index of 0.652. An online risk calculator was also generated. CONCLUSIONS: To the best of our knowledge, this is the first predictive nomogram for biochemical outcomes after primary whole gland cryoablation of the prostate using socio-demographic, pretreatment, clinical, and prostate biopsy data. Our nomogram and online risk calculator can guide both patients and urologists for shared decision making regarding definitive treatment options.