A systematic review on the outcomes of local anaesthetic transperineal prostate biopsy.

OBJECTIVE: To conduct a systematic review of the literature to assess the diagnostic ability, complication rate, patient tolerability, and cost of local anaesthetic (LA) transperineal prostate biopsy. METHODS: Two reviewers searched Medline, the Cochrane Library, and Embase for publications on LA transperineal prostate biopsy up to March 2021. Outcomes of interest included cancer detection rates, complication rates, pain assessments and cost. RESULTS: A total of 35 publications with 113 944 men were included in this review. The cancer detection rate for LA transperineal prostate biopsy in patients undergoing primary biopsy was 52% (95% confidence interval [CI] 0.45-0.60; I2 = 97) and the clinically significant cancer detection rate (Gleason≥3 + 4) was 37% (95% CI 0.24-0.52; I2 = 99%). The rate of infection-related complications in the included studies was 0.15% (95% CI 0.0000-0.0043; I2 = 86). The LA transperineal procedures had a low rate of procedural abandonment (26/6954, 0.37%), with the greatest pain scores measured during LA administration. No formal cost analyses on LA transperineal prostate biopsies were identified in the literature. The overall risk of bias in the included studies was high, with considerable study heterogeneity and publication bias. CONCLUSION: Transperineal prostate biopsy performed under LA is a viable option for centres interested in avoiding the risk of infection associated with transrectal biopsy, and the logistical burden of general anaesthesia. Further investigation into LA transperineal prostate biopsy with comparative studies is warranted for its consideration as the standard in prostate biopsy technique.

Long-term oncological outcomes of the Agarwal loop-ligation technique for management of the distal ureter during laparoscopic radical nephroureterectomy.

OBJECTIVES: To describe the Agarwal loop-ligation technique for the management of the distal ureter during laparoscopic radical nephroureterectomy (LRNU) for upper tract urothelial carcinoma (UTUC) and report on long-term oncological outcomes. PATIENTS AND METHODS: In the Agarwal loop-ligation technique, the distal ureteric stump is controlled using endoscopic Endoloop® or PolyLoop® ligation to ensure en bloc excision of the bladder cuff and prevent spillage of upper tract urine into the perivesical space. A retrospective review of the medical records of 76 patients who underwent the Agarwal loop-ligation technique for UTUC at participating centres from July 2004 to December 2017 was performed. Data collected included demographics, perioperative, and long-term oncological outcomes. Survival was calculated using Kaplan-Meier survival analyses. RESULTS AND LIMITATIONS: A total of 76 patients were included. The median age was 71.5 years and median operative time was 4.3 h. The intramural ureter and bladder cuff were completely excised in all patients. Distal surgical margins were clear in all, with only two patients found to have tumour extending to the circumferential surgical margin. There were no cases of perivesical recurrence or port-site metastasis. The 5-year bladder, local, and contralateral recurrence-free survival was 59.6%, 89.0% and 93.5%, respectively. Metastasis-free survival at 5-years was 73.5%. The 5-year overall survival and cancer-specific survival rates were 70.3% and 84.7%, respectively. CONCLUSIONS: We have described the Agarwal loop-ligation technique for the management of the distal ureter in LRNU. This technique complies with oncological principles outlined in the European Association of Urology guidelines, which minimises tumour spillage. Long-term oncological outcomes are satisfactory, with no cases of perivesical recurrence detected in this series.

Training in minimally invasive surgery in urology: European Association of Urology/International Consultation of Urological Diseases consultation.

OBJECTIVES: To describe the progress being made in training for minimally invasive surgery (MIS) in urology. METHODS: A group of experts in the field provided input to agree on recommendations for MIS training. A literature search was carried out to identify studies on MIS training, both in general and specifically for urological procedures. RESULTS: The literature search showed the rapidly developing options for e-learning, box and virtual training, and suggested that box training is a relatively cheap and effective means of improving laparoscopic skills. Development of non-technical skills is an integral part of surgical skills training and should be included in training curricula. The application of modular training in surgical procedures showed more rapid skills acquisition. Training curricula for MIS in urology are being developed in both the USA and Europe. CONCLUSION: Training in MIS has shifted from 'see-one-do-one-teach-one' to a structured learning, from e-learning to skills laboratory and modular training settings.

Corrigendum to "RPN (Radius, Position of tumour, iNvasion of renal sinus) Classification and Nephrometry Scoring System: An Internationally Developed Clinical Classification To Describe the Surgical Difficulty for Renal Masses for Which Robotic Partial Nephrectomy Is Planned" [Eur. Urol. Open Sci. 54 (2023) 33-42].

[This corrects the article DOI: 10.1016/j.euros.2023.05.007.].

A Systematic Review of Intra- and Postoperative Complication Reporting and Grading in Urological Surgery: Understanding the Pitfalls and a Path Forward.

CONTEXT: Surgical outcomes and patient morbidity are often surrogate markers of health care quality and efficiency. These parameters can only be used with confidence if the reporting and grading of intra- and postoperative complications are reliable and reproducible. Without uniformity and regulation, the risk of under-reporting, and thus significant underestimation of the burden of intra- and postoperative morbidity, is high and should be of great concern to the international surgical community. OBJECTIVE: To assess the quality and utility of currently available reporting and classification systems for intra- and postoperative complications, recognise their advantages and pitfalls, discuss the overall implications of these systems for urological surgery, and identify potential solutions for future reporting and classification systems. EVIDENCE ACQUISITION: A comprehensive search was performed using multiple reputable databases and trial registries up to October 25, 2022. Only studies that adhered to predefined inclusion criteria were included. Study selection and data extraction were independently performed by two review authors. The review was performed according to strict methodological guidelines in line with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 statement. EVIDENCE SYNTHESIS: A total of 13 papers highlighting 13 various complication systems were critically assessed in this review. All studies proposed an intra- or postoperative complication reporting or grading system that was surgically related. At present, there is no single instrument in clinical practice to account for all relevant complication data. Six of the 13 studies were clinically validated (46%) and only three studies were urology-focused (23%). Meta-analysis was not possible. CONCLUSIONS: Current individual complication tools are flawed, so there is a need for a novel, all-inclusive, specialty-specific reporting and classification system for intra- and postoperative complications. If successfully validated and integrated worldwide, such an instrument would have the potential to play a significant role in reshaping efficiency in health care systems and improving surgical and patient quality of care. PATIENT SUMMARY: Current tools for reporting and classifying complications during and after surgery underestimate how burdensome such complications can be for patients. We summarise the reporting and classification tools currently available, discuss their advantages and drawbacks, and propose potential solutions for future systems. Our review can help in better understanding the changes required for future tools and how to improve overall surgical outcomes for patients.

Comparison of Robotic vs Open Cystectomy: A Systematic Review.

BACKGROUND: The benefits of a robot-assisted radical cystectomy (RARC) compared to an open approach is still under debate. Initial data on RARC were from trials where urinary diversion was performed by an extracorporeal approach, which does not represent a completely minimally invasive procedure. There are now updated data for RARC with intracorporeal urinary diversion that add to the evidence profile of RARC. OBJECTIVE: To perform a systematic review and meta-analysis of the effectiveness of RARC compared with open radical cystectomy (ORC). MATERIALS AND METHODS: Multiple databases were searched up to May 2022. We included randomised trials in which patients underwent RARC and ORC. Oncological and safety outcomes were assessed. RESULTS: Seven trials of 907 participants were included. There were no differences seen in primary outcomes: disease progression [RR 0.98, 95% CI 0.78 to 1.23], major complications [RR 0.95, 95% CI 0.72 to 1.24] and quality of life [SMD 0.05, 95% CI -0.13 to 0.38]. RARC resulted in a decreased risk of perioperative blood transfusion [RR 0.57, 95% CI 0.43 to 0.76], wound complications [RR 0.34, 95% CI 0.21 to 0.55] and reduced length of hospital stay [MD -0.62 days, 95% CI -1.11 to -0.13]. However, there was an increased risk of developing a ureteric stricture [RR 4.21, 95% CI 1.07 to 16.53] in the RARC group and a prolonged operative time [MD 70.4 minutes, 95% CI 34.1 to 106.7]. The approach for urinary diversion did not impact outcomes. CONCLUSION: RARC is an oncologically safe procedure compared to ORC and provides the benefits of a minimally invasive approach. There was an increased risk of developing a ureteric stricture in patients undergoing RARC that warrants further investigation. There was no difference in oncological outcomes between approaches.

Same day discharge for robot-assisted radical prostatectomy: a prospective cohort study documenting an Australian approach.

BACKGROUND: The introduction of robotic surgical systems has significantly impacted urological surgery, arguably more so than other surgical disciplines. The focus of our study was length of hospital stay - patients have traditionally been discharged day 1 post-robot-assisted radical prostatectomy (RARP), however, during the ongoing COVID-19 pandemic and consequential resource limitations, our centre has facilitated a cohort of same-day discharges with initial success. METHODS: We conducted a prospective tertiary single-centre cohort study of a series of all patients (n = 28) - undergoing RARP between January and April 2021. All patients were considered for a day zero discharge pathway which consisted of strict inclusion criteria. At follow-up, each patient's perspective on their experience was assessed using a validated post-operative satisfaction questionnaire. Data were reviewed retrospectively for all those undergoing RARP over the study period, with day zero patients compared to overnight patients. RESULTS: Overall, 28 patients 20 (71%) fulfilled the objective criteria for day zero discharge. Eleven patients (55%) agreed pre-operatively to day zero discharge and all were successfully discharged on the same day as their procedure. There was no statistically significant difference in age, BMI, ASA, Charlson score or disease volume. All patients indicated a high level of satisfaction with their procedure. Median time from completion of surgery to discharge was 426 min (7.1 h) in the day zero discharge cohort. CONCLUSION: Day zero discharge for RARP appears to deliver high satisfaction, oncological and safety outcomes. Therefore, our study demonstrates early success with unsupported same-day discharge in carefully selected and pre-counselled patients.

RPN (Radius, Position of tumour, iNvasion of renal sinus) Classification and Nephrometry Scoring System: An Internationally Developed Clinical Classification To Describe the Surgical Difficulty for Renal Masses for Which Robotic Partial Nephrectomy Is Planned.

Background: The surgical difficulty of partial nephrectomy (PN) varies depending on the operative approach. Existing nephrometry classifications for assessment of surgical difficulty are not specific to the robotic approach. Objective: To develop an international robotic-specific classification of renal masses for preoperative assessment of surgical difficulty of robotic PN. Design setting and participants: The RPN classification (Radius, Position of tumour, iNvasion of renal sinus) considers three parameters: tumour size, tumour position, and invasion of the renal sinus. In an international survey, 45 experienced robotic surgeons independently reviewed de-identified computed tomography images of 144 patients with renal tumours to assess surgical difficulty of robot-assisted PN using a 10-point Likert scale. A separate data set of 248 patients was used for external validation. Outcome measurements and statistical analysis: Multiple linear regression was conducted and a risk score was developed after rounding the regression coefficients. The RPN classification was correlated with the surgical difficulty score derived from the international survey. External validation was performed using a retrospective cohort of 248 patients. RPN classification was also compared with the RENAL (Radius; Exophytic/endophytic; Nearness; Anterior/posterior; Location), PADUA (Preoperative Aspects and Dimensions Used for Anatomic), and SPARE (Simplified PADUA REnal) scoring systems. Results and limitation: The median tumour size was 38 mm (interquartile range 27-49). The majority (81%) of renal tumours were peripheral, followed by hilar (12%) and central (7.6%) locations. Noninvasive and semi-invasive tumours accounted for 37% each, and 26% of the tumours were invasive. The mean surgical difficulty score was 5.2 (standard deviation 1.9). Linear regression analysis indicated that the RPN classification correlated very well with the surgical difficulty score (R2 = 0.80). The R2 values for the other scoring systems were: 0.66 for RENAL, 0.75 for PADUA, and 0.70 for SPARE. In an external validation cohort, the performance of all four classification systems in predicting perioperative outcomes was similar, with low R2 values. Conclusions: The proposed RPN classification is the first nephrometry system to assess the surgical difficulty of renal masses for which robot-assisted PN is planned, and is a useful tool to assist in surgical planning, training and data reporting. Patient summary: We describe a simple classification system to help urologists in preoperative assessment of the difficulty of robotic surgery for partial kidney removal for kidney tumours.

Lymphovascular Invasion at the Time of Radical Prostatectomy Adversely Impacts Oncological Outcomes.

Lymphovascular invasion, whereby tumour cells or cell clusters are identified in the lumen of lymphatic or blood vessels, is thought to be an essential step in disease dissemination. It has been established as an independent negative prognostic indicator in a range of cancers. We therefore aimed to assess the impact of lymphovascular invasion at the time of prostatectomy on oncological outcomes. We performed a multicentre, retrospective cohort study of 3495 men who underwent radical prostatectomy for localised prostate cancer. Only men with negative preoperative staging were included. We assessed the relationship between lymphovascular invasion and adverse pathological features using multivariable logistic regression models. Kaplan-Meier curves and Cox proportional hazard models were created to evaluate the impact of lymphovascular invasion on oncological outcomes. Lymphovascular invasion was identified in 19% (n = 653) of men undergoing prostatectomy. There was an increased incidence of lymphovascular invasion-positive disease in men with high International Society of Urological Pathology (ISUP) grade and non-organ-confined disease (p < 0.01). The presence of lymphovascular invasion significantly increased the likelihood of pathological node-positive disease on multivariable logistic regression analysis (OR 15, 95%CI 9.7-23.6). The presence of lymphovascular invasion at radical prostatectomy significantly increased the risk of biochemical recurrence (HR 2.0, 95%CI 1.6-2.4). Furthermore, lymphovascular invasion significantly increased the risk of metastasis in the whole cohort (HR 2.2, 95%CI 1.6-3.0). The same relationship was seen across D'Amico risk groups. The presence of lymphovascular invasion at the time of radical prostatectomy is associated with aggressive prostate cancer disease features and is an indicator of poor oncological prognosis.

Defining Prostatic Vascular Pedicle Recurrence and the Anatomy of Local Recurrence of Prostate Cancer on Prostate-specific Membrane Antigen Positron Emission Tomography/Computed Tomography.

Background: The term local recurrence in prostate cancer is considered to mean persistent local disease in the prostatic bed, most commonly at the site of the vesicourethral anastomosis (VUA). Since the introduction of prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) and magnetic resonance imaging for assessment of early biochemical recurrence (BCR), we have found histologically confirmed prostate cancer in the prostatic vascular pedicle (PVP). If a significant proportion of local recurrences are distant to the VUA, it may be possible to alter adjuvant and salvage radiation fields in order to reduce the potential morbidity of radiation in selected patients. Objective: To describe PVP local recurrence and to map the anatomic pattern of prostate bed recurrence on PSMA PET/CT. Design setting and participants: This was a retrospective multicentre study of 185 patients imaged with PSMA PET/CT following radical prostatectomy (RP) between January 2016 and November 2018. All patient data and clinical outcomes were prospectively collected. Recurrences were documented according to anatomic location. For patients presenting with local recurrence, the precise location of the recurrence within the prostate bed was documented. Intervention: PSMA PET/CT for BCR following RP. Results and limitations: A total of 43 local recurrences in 41/185 patients (22%) were identified. Tumour recurrence at the PVP was found in 26 (63%), VUA in 15 (37%), and within a retained seminal vesicle and along the anterior rectal wall in the region of the neurovascular bundle in one (2.4%) each. Histological and surgical evidence of PVP recurrence was acquired in two patients. The study is limited by its retrospective nature with inherent selection bias. This is an observational study reporting on the anatomy of local recurrence and does not include follow-up for patient outcomes. Conclusions: Our study showed that prostate cancer can recur in the PVP and is distant to the VUA more commonly than previously thought. This may have implications for RP technique and for the treatment of selected patients in the local recurrence setting. Patient summary: We investigated more precise identification of the location of tumour recurrence after removal of the prostate for prostate cancer. We describe a new definition of local recurrence in an area called the prostatic vascular pedicle. This new concept may alter the treatment recommended for recurrent disease.

A review of simulation training and new 3D computer-generated synthetic organs for robotic surgery education.

We conducted a comprehensive review of surgical simulation models used in robotic surgery education. We present an assessment of the validity and cost-effectiveness of virtual and augmented reality simulation, animal, cadaver and synthetic organ models. Face, content, construct, concurrent and predictive validity criteria were applied to each simulation model. There are six major commercial simulation machines available for robot-assisted surgery. The validity of virtual reality (VR) simulation curricula for psychomotor assessment and skill acquisition for the early phase of robotic surgery training has been demonstrated. The widespread adoption of VR simulation has been limited by the high cost of these machines. Live animal and cadavers have been the accepted standard for robotic surgical simulation since it began in the early 2000s. Our review found that there is a lack of evidence in the literature to support the use of animal and cadaver for robotic surgery training. The effectiveness of these models as a training tool is limited by logistical, ethical, financial and infection control issues. The latest evolution in synthetic organ model training for robotic surgery has been driven by new 3D-printing technology. Validated and cost-effective high-fidelity procedural models exist for robotic surgery training in urology. The development of synthetic models for the other specialties is not as mature. Expansion into multiple surgical disciplines and the widespread adoption of synthetic organ models for robotic simulation training will require the ability to engineer scalability for mass production. This would enable a transition in robotic surgical education where digital and synthetic organ models could be used in place of live animals and cadaver training to achieve robotic surgery competency.

There is a Need for a Universal Language in the Reporting and Grading of Complication and Intervention Events to Ensure Comparability and Improvement of Surgical Care.

To enhance the clarity and quality of complication reporting and grading for clinicians and patients, the CAMUS-Collaboration aims to develop the following: (1) a data dictionary; (2) parameters required for reporting; (3) risk-based reporting; (4) nursing and patient opinions; and (5) prospective reporting and grading of short- and long-term complications.

Phase 2 Study of Neoadjuvant FGFR Inhibition and Androgen Deprivation Therapy Prior to Prostatectomy.

BACKGROUND: Disease recurrence is common following prostatectomy in patients with localised prostate cancer with high-risk features. Although androgen deprivation therapy increases the rates of organ-confined disease and negative surgical margins, there is no significant benefit on disease recurrence. Multiple lines of evidence suggest that (Fibroblast Growth Factor/Fibroblast Growth Factor Receptor) FGF/FGFR-signalling is important in supporting prostate epithelial cell survival in hostile conditions, including acute androgen deprivation. Given the recent availability of oral FGFR inhibitors, we investigated whether combination therapy could improve tumour response in the neo-adjuvant setting. METHODS: We conducted an open label phase II study of the combination of erdafitinib (3 months) and androgen deprivation therapy (4 months) in men with localised prostate cancer with high-risk features prior to prostatectomy using a Simon's 2 stage design. The co-primary endpoints were safety and tolerability and pathological response in the prostatectomy specimen. The effect of treatment on residual tumours was explored by global transcriptional profiling with RNA-sequencing. RESULTS: Nine patients were enrolled in the first stage of the trial. The treatment combination was poorly tolerated. Erdafitinib treatment was discontinued early in six patients, three of whom also required dose interruptions/reductions. Androgen deprivation therapy for 4 months was completed in all patients. The most common adverse events were hyperphosphataemia, taste disturbance, dry mouth and nail changes. No patients achieved a complete pathological response, although patients who tolerated erdafitinib for longer had smaller residual tumours, associated with reduced transcriptional signatures of epithelial cell proliferation. CONCLUSIONS: Although there was a possible enhanced anti-tumour effect of androgen deprivation therapy in combination with erdafitnib in treatment naïve prostate cancer, the poor tolerability in this patient population prohibits the use of this combination in this setting.

Protocol for CAMUS Delphi Study: A Consensus on Comprehensive Reporting and Grading of Complications After Urological Surgery.

BACKGROUND: Reproducible assessment of postoperative complications is essential for reliable evaluation of quality of care to enable comparison between healthcare centres and ensure transparent patient counselling. Currently, significant discrepancies exist in complication reporting and grading due to heterogeneous definitions and methodologies. OBJECTIVE: To develop a standardised and reproducible assessment of perioperative complications and overall associated morbidity, to allow for the construction of a uniform language for complication reporting and grading. DESIGN, SETTING, AND PARTICIPANTS: The 12-part REDCap-based Delphi survey was developed in conjunction with methodologist review and experienced urologist opinion. International urologists, anaesthetists, and intensive care unit specialists will be included. A minimum sample size of 750 participants (500 urologists and 250 critical care specialities) is targeted. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The survey assesses participant demographics, opinion on complication reporting and the proposed Complications After Major & Minor Urological Surgery (CAMUS) reporting recommendations, grading of intervention events using the existing Clavien-Dindo classification and the proposed CAMUS classification, and rating of various clinical scenarios. Consensus will be defined as ≥75% majority agreement. If consensus is not reached, then subsequent Delphi rounds will be performed under steering committee guidance. RESULTS AND LIMITATIONS: Twenty-one participants completed the draft survey. The median survey completion time was 128 min (interquartile range 88-135). The survey revealed that 90% of participants believe that the current complication classification systems are useful but inaccurate, while 100% of participants believe that there is a universal demand for reporting consensus. Several amendments were made following feedback. Limitations include complexity of the proposed supplemental grades and time to completion of the survey. CONCLUSIONS: To ensure comprehensive and comparable complication reporting and grading across centres worldwide, a conclusive uniform language for complication reporting must be created. We intend to address shortcomings of the current complication reporting and classification systems with a new CAMUS classification system developed through multidisciplinary expert consensus obtained through a Delphi survey. Ultimately, standardisation of urological complication reporting and grading may improve patient counselling and quality of care. PATIENT SUMMARY: The reporting and grading of operative complications that occur during or after an operation and associated costs provide a means to stratify quality of patient care. Current complication reporting and classification systems are not standardised and somewhat inaccurate, and thus significantly underestimate patient morbidity and surgical risk. This Delphi survey will provide the basis for the creation of a uniform complication reporting and grading system. Our new system may allow improved reporting and grading between centres, and ultimately improve patient counselling and care.

Active involvement of nursing staff in reporting and grading complication-intervention events-Protocol and results of the CAMUS Pilot Nurse Delphi Study.

Objectives: The aim of this study is to gain experienced nursing perspective on current and future complication reporting and grading in Urology, establish the CAMUS CCI and quality control the use of the Clavien-Dindo Classification (CDC) in nursing staff. Subjects and Methods: The 12-part REDCap-based Delphi survey was developed in conjunction with expert nurse, urologist and methodologist input. Certified local and international inpatient and outpatient nurses specialised in urology, perioperative nurses and urology-specific advanced practice nurses/nurse practitioners will be included. A minimum sample size of 250 participants is targeted. The survey assesses participant demographics, nursing experience and opinion on complication reporting and the proposed CAMUS reporting recommendations; grading of intervention events using the existing CDC and the proposed CAMUS Classification; and rating various clinical scenarios. Consensus will be defined as ≥75% agreement. If consensus is not reached, subsequent Delphi rounds will be performed under Steering Committee guidance. Results: Twenty participants completed the pilot survey. Median survey completion time was 58 min (IQR 40-67). The survey revealed that 85% of nursing participants believe nurses should be involved in future complication reporting and grading but currently have poor confidence and inadequate relevant background education. Overall, 100% of participants recognise the universal demand for reporting consensus and 75% hold a preference towards the CAMUS System. Limitations include variability in nursing experience, complexity of supplemental grades and survey duration. Conclusion: The integration of experienced nursing opinion and participation in complication reporting and grading systems in a modern and evolving hospital infrastructure may facilitate the assimilation of otherwise overlooked safety data. Incorporation of focused teaching into routine nursing education will be essential to ensure quality control and stimulate awareness of complication-related burden. This, in turn, has the potential to improve patient counselling and quality of care.

The utility of magnetic resonance imaging in prostate cancer diagnosis in the Australian setting.

Objectives: To investigate the utility of Magnetic Resonance Imaging (MRI) for prostate cancer diagnosis in the Australian setting. Patients and methods: All consecutive men who underwent a prostate biopsy (transperineal or transrectal) at Royal Melbourne Hospital between July 2017 to June 2019 were included, totalling 332 patients. Data were retrospectively collected from patient records. For each individual patient, the risk of prostate cancer diagnosis at biopsy based on clinical findings was determined using the European Randomized study of Screening for Prostate Cancer (ERSPC) risk calculator, with and without incorporation of MRI findings. Results: MRI has good diagnostic accuracy for clinically significant prostate cancer. A PI-RADS 2 or lower finding has a negative predictive value of 96% for clinically significant cancer, and a PI-RADS 3, 4 or 5 MRI scan has a sensitivity of 93%. However, MRI has a false negative rate of 6.5% overall for clinically significant prostate cancers. Pre- biopsy MRI may reduce the number of unnecessary biopsies, as up to 50.0% of negative or ISUP1 biopsies have MRI PI-RADS 2 or lower. Incorporation of MRI findings into the ERSPC calculator improved predictive performance for all prostate cancer diagnoses (AUC 0.77 vs 0.71, P = .04), but not for clinically significant cancer (AUC 0.89 vs 0.87, P = .37). Conclusion: MRI has good sensitivity and negative predictive value for clinically significant prostate cancers. It is useful as a pre-biopsy tool and can be used to significantly reduce the number of unnecessary prostate biopsies. However, MRI does not significantly improve risk predictions for clinically significant cancers when incorporated into the ERSPC risk calculator.

Loss of SNAI2 in Prostate Cancer Correlates With Clinical Response to Androgen Deprivation Therapy.

PURPOSE: Androgen receptor (AR) signaling is important in prostate cancer progression, and therapies that target this pathway have been the mainstay of treatment for advanced disease for over 70 years. Tumors eventually progress despite castration through a number of well-characterized mechanisms; however, little is known about what determines the magnitude of response to short-term pathway inhibition. METHODS: We evaluated a novel combination of AR-targeting therapies (degarelix, abiraterone, and bicalutamide) and noted that the objective patient response to therapy was highly variable. To investigate what was driving treatment resistance in poorly responding patients, as a secondary outcome we comprehensively characterized pre- and post-treatment samples using both whole-genome and RNA sequencing. RESULTS: We find that resistance following short-term treatment differs molecularly from typical progressive castration-resistant disease, associated with transcriptional reprogramming, to a transitional epithelial-to-mesenchymal transition (EMT) phenotype rather than an upregulation of AR signaling. Unexpectedly, tolerance to therapy appears to be the default state, with treatment response correlating with the prevalence of tumor cells deficient for SNAI2, a key regulator of EMT reprogramming. CONCLUSION: We show that EMT characterizes acutely resistant prostate tumors and that deletion of SNAI2, a key transcriptional regulator of EMT, correlates with clinical response.

Ductal variant prostate carcinoma is associated with a significantly shorter metastasis-free survival.

BACKGROUND: Ductal adenocarcinoma is an uncommon prostate cancer variant. Previous studies suggest that ductal variant histology may be associated with worse clinical outcomes, but these are difficult to interpret. To address this, we performed an international, multi-institutional study to describe the characteristics of ductal adenocarcinoma, particularly focussing on the effect of presence of ductal variant cancer on metastasis-free survival. METHODS: Patients with ductal variant histology from two institutional databases who underwent radical prostatectomies were identified and compared with an independent acinar adenocarcinoma cohort. After propensity score matching, the effect of the presence of ductal adenocarcinoma on time to biochemical recurrence, initiation of salvage therapy and the development of metastatic disease was determined. Deep whole-exome sequencing was performed for selected cases (n = 8). RESULTS: A total of 202 ductal adenocarcinoma and 2037 acinar adenocarcinoma cases were analysed. Survival analysis after matching demonstrated that patients with ductal variant histology had shorter salvage-free survival (8.1 versus 22.0 months, p = 0.03) and metastasis-free survival (6.7 versus 78.6 months, p < 0.0001). Ductal variant histology was consistently associated with RB1 loss, as well as copy number gains in TAP1, SLC4A2 and EHHADH. CONCLUSIONS: The presence of any ductal variant adenocarcinoma at the time of prostatectomy portends a worse clinical outcome than pure acinar cancers, with significantly shorter times to initiation of salvage therapies and the onset of metastatic disease. These features appear to be driven by uncoupling of chromosomal duplication from cell division, resulting in widespread copy number aberration with specific gain of genes implicated in treatment resistance.

Vulvar hematoma secondary to spontaneous rupture of the internal iliac artery: clinical review.

Vulvar hematomas occur rarely outside the obstetric population but may present after other trauma to the pelvis or perineum. Spontaneous rupture of the internal iliac artery is described mostly in the presence of an aneurysm, with atherosclerosis, connective tissue disease, infection, and trauma as causative factors. It most often presents with abdominal pain and neurologic or urologic symptoms. We present an unusual case of a spontaneous rupture of the internal iliac artery that presented as a vulvar hematoma in a nulliparous woman that was successfully treated with selective arterial embolization and surgical evacuation. The literature is reviewed and management options discussed.