Myoid gonadal stromal tumours are characterised by recurrent chromosome-level copy number gains: molecular assessment of a multi-institutional series.

Myoid gonadal stromal tumours (MGST) represent a rare type of testicular sex cord-stromal tumour that has recently been recognised as a distinct entity by the World Health Organization (WHO) classification of genitourinary tumours. MGSTs affect adult men and have been reported to behave in an indolent fashion. Histologically, MGSTs are pure spindle cell neoplasms that coexpress SMA and S100 protein. Given that the molecular features of these neoplasms remain largely undescribed, we evaluated a multi-institutional series of MGSTs using DNA and RNA sequencing. This study included 12 tumours from 12 patients aged 28 to 57 years. Tumour sizes ranged from 0.6 to 4.3 cm. Aggressive histologic features, such as vascular invasion, necrosis, invasive growth, and atypical mitoses were invariably absent. Mitotic activity was low, with a median of less than 1 mitosis per 10 high power fields (HPF; maximum: 3 mitoses per 10 HPF). Molecular analyses did not identify recurrent mutations or gene fusions. All cases with interpretable copy number variant data (9/10 cases sequenced successfully) demonstrated a consistent pattern of chromosome arm-level and whole-chromosome-level copy number gains indicative of ploidy shifts, with recurrent gains involving chromosomes 3, 6, 7, 8, 9, 11, 12, 14q, 15q, 17, 18q, 20, and 21q. Similar findings have also been recognised in pure spindle cell and spindle-cell predominant sex cord-stromal tumours without S100 protein expression. MGSTs are characterised by ploidy shifts and may be part of a larger spectrum of spindle cell-predominant sex cord-stromal tumours, including cases without S100 protein expression.

Prostate cancer local staging using biparametric MRI: assessment and comparison with multiparametric MRI.

PURPOSE: The value of adding dynamic contrast-enhanced (DCE) imaging to T2-weighted (T2W) magnetic resonance imaging (MRI) and diffusion-weighted imaging (DWI) to improve the detection and staging of prostate cancer (PCa) is unclear. The aim of this retrospective study was to compare the diagnostic performance of non-contrast biparametric MRI (bpMRI) with multiparametric MRI (mpMRI), for local staging of PCa. METHODS: Ninety-two patients who underwent prostate MRI on a 3-Tesla MRI system before radical prostatectomy for PCa were included retrospectively. Four readers independently assigned a Likert score (ranging from 1 to 5) for predicting extra-prostatic extension (EPE) on T2W + DWI (bpMRI) and then on T2W + DWI + DCE imaging (mpMRI). MRI-based staging results were compared with radical prostatectomy histology. A prediction of EPE generalized linear mixed model was used to assess the added-value of DCE and discriminative power of staging accuracy by area under the receiver-operating curve (AUC ROC). RESULTS: AUC was not significantly improved by DCE (mpMRI, AUC = 0.73 [95%CI: 0.655‒0.827] vs. bpMRI, AUC = 0.76 [95%CI: 0.681‒0.846]). After applying a selection procedure, only MRI criteria were retained in a multivariate model. The following criteria were significantly associated with local extension: localization in the peripheral zone (p < 0.001), maximal diameter of the lesion (<0.0001), curvilinear capsular contact on T2W (p < 0.0001), capsular irregularity on T2W (p < 0.0001), bulging on T2W (p < 0.001) and seminal vesicle hypo-signal (p < 0.001). CONCLUSION: Use of bpMRI did not result in a decrease in local staging accuracy.

Risk Stratification Tools and Prognostic Models in Non-muscle-invasive Bladder Cancer: A Critical Assessment from the European Association of Urology Non-muscle-invasive Bladder Cancer Guidelines Panel.

CONTEXT: This review focuses on the most widely used risk stratification and prediction tools for non-muscle-invasive bladder cancer (NMIBC). OBJECTIVE: To assess the clinical use and relevance of risk stratification and prediction tools to enhance clinical decision making and counselling of patients with NMIBC. EVIDENCE ACQUISITION: The most frequent, currently used risk stratification tools and prognostic models for NMIBC patients were identified by the members of the European Association of Urology (EAU) Guidelines Panel on NMIBC. EVIDENCE SYNTHESIS: The 2006 European Organization for Research and Treatment of Cancer (EORTC) risk tables are the most widely used and validated tools for risk stratification and prognosis prediction in NMIBC patients. The EAU risk categories constitute a simple alternative to the EORTC risk tables and can be used for comparable risk stratification. In the subgroup of NMIBC patients treated with a short maintenance schedule of bacillus Calmette-Guerin (BCG), the Club Urológico Español de Tratamiento Oncológico (CUETO) scoring model is more accurate than the EORTC risk tables. Both the EORTC risk tables and the CUETO scoring model overestimate the recurrence and progression risks in patients treated according to current guidelines. The new concept of conditional recurrence and progression estimates is very promising during follow-up but should be validated. CONCLUSIONS: Risk stratification and prognostic models enable outcome comparisons and standardisation of treatment and follow-up. At present, none of the available risk stratification and prognostic models reflects current standards of treatment. The EORTC risk tables and CUETO scoring model should be updated with previously unavailable data and recalculated. PATIENT SUMMARY: Non-muscle-invasive bladder cancer is a heterogeneous disease. A risk-based therapeutic approach is recommended. We present available risk stratification and prediction tools and the degree of their validation with the aim to increase their use in everyday clinical practice.

The European Prostate Cancer Centres of Excellence: A Novel Proposal from the European Association of Urology Prostate Cancer Centre Consensus Meeting.

BACKGROUND: High-quality management of prostate cancer is needed in the fields of clinics, research, and education. OBJECTIVE: The objective of this project was to develop the concept of "European Prostate Cancer Centres of Excellence" (EPCCE), with the specific aim of identifying European centres characterised by high-quality cancer care, research, and education. DESIGN, SETTING, AND PARTICIPANTS: A task force of experts aimed at identifying the general criteria to define the EPCCE. Discussion took place in conference calls and by e-mail from March 2017 to November 2017, and the final consensus meeting named "European Association of Urology (EAU) Prostate Cancer Centre Consensus Meeting" was held in Barcelona on November 16, 2017. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The required criteria were grouped into three main steps: (1) clinics, (2) research, and (3) education. A quality control approach for the three steps was defined. RESULTS AND LIMITATIONS: The definition of EPCCE consisted of the following steps: (1) clinical step-five items were identified and classified as core team, associated services, multidisciplinary approach, diagnostic pathway, and therapeutic pathway; (2) research step-internal monitoring of outcomes was required; clinical data had to be collected through a prespecified database, clinical outcomes had to be periodically assessed, and prospective trials had to be conducted; (3) educational step-it consists of structured fellowship programmes of 1yr, including 6mo of research and 6mo of clinics; and (4) quality assurance and quality control procedures, related to the quality assessment of the previous three steps. A limitation of this project was that the definition of standards and items was mainly based on a consensus among experts rather than being an evidence-based process. CONCLUSIONS: The EAU Prostate Cancer Centre Consensus Meeting defined the criteria for the identification of the EPCCE in the fields of clinics, research, and education. The inclusion of a quality control approach represents the novelty that supports the excellence of these centres. PATIENT SUMMARY: A task force of experts defined the criteria for the identification of European Prostate Cancer Centres of Excellence, in order to certify the high-quality centres for prostate cancer management.

Prevalence, management, and prognosis of bladder cancer in patients with neurogenic bladder: A systematic review.

AIM: To perform a systematic review of the literature regarding epidemiology, diagnosis, management and prognosis of bladder cancer in the neuro-urological patient population, in order to serve as a basis for future recommendations and research. METHODS: A systematic review was performed according to the PRISMA-Preferred Reporting Items for Systematic Reviews and Meta-Analyzes Statement. Embase was searched for studies providing data on epidemiology, diagnosis, management and prognosis of bladder cancer in neuro-urological patients. RESULTS: After screening 637 abstracts, 15 studies (13 retrospective and 2 prospective studies) were included in this study. We identified 332 patients (0.3%) who were diagnosed with bladder cancer. This mostly affected mostly men (59.3%) and spinal cord injured patients (98.8%). Mean age at diagnosis was 56.1 years. Bladder cancer occurred after a long period of evolution of the neurological disease (24.9 years). Gross hematuria was the predominating presenting symptom (31.6% of cases). Indwelling urethral or supra-pubic catheters were used in 44.5% of patients. The most frequent histological subtype of bladder cancer was transitional cell carcinoma (53.1%), followed by squamous cell carcinoma (33.5%). Muscle-invasive bladder cancer was reported in 67.7% of patients. The mean cancer-specific mortality rate was of 47.1%. CONCLUSIONS: The prevalence and high mortality rate of bladder cancer in neuro-urological patients underlines the importance of long-term follow-up in this specific population. This highlights the necessity of further studies in this field.

Immunochemical and molecular assessment of urothelial neoplasms and aspects of the 2016 World Health Organization classification.

The new World Health Organization classification of tumours of the urinary system and male genital organs (4th edn) has several changes from previous versions, and was published in January 2016. New pathways have been discovered in the development of bladder cancer, and were included in this new classification. Guidance from the International Collaboration on Cancer Reporting (ICCR) helped to clarify open questions, in conjunction with the new classification. The histological groups of urothelial carcinoma evolved. Grading remained the same, despite controversy among European urologists. Substaging of pT1 tumours is recommended for the first time, and the ICCR has made recommendations on how to report this. Furthermore, worldwide advice has been published on the use of immunohistochemistry, and recommendations have been made to try to standardize the handling of bladder cancer from a histopathological point of view. At a molecular level, bladder cancer groups have been stratified, and an upcoming molecular classification permits a novel view of this malignancy. This review will try to summarize the most important changes.

Noninvasive contrast-enhanced US quantitative assessment of tumor microcirculation in a murine model: effect of discontinuing anti-VEGF therapy.

PURPOSE: To determine, by using contrast material-enhanced ultrasonography (US), how quickly renal tumors grafted in mice begin to revascularize after stopping bevacizumab treatment. MATERIALS AND METHODS: All experiments were approved by the regional ethics committee. A human tumor cell line SK-NEP-1 was grafted at day 0 in the left kidney of 50 nude mice. Forty-two mice developed tumors and longitudinal follow-up was performed on 32 surviving mice. From day 13, 14 controls received biweekly saline; 11 mice received biweekly bevacizumab until day 35 (continuous); and seven received biweekly bevacizumab until day 22, then biweekly placebo until day 35 (discontinued). Contrast-enhanced US was performed on days 13, 14, 22, 27, and 35. Once the injected contrast material distribution reached an equilibrium phase, high-acoustic pressure pulses were applied to destroy microbubbles in the capillary bed in the imaged plane. Reperfusion was monitored, and time-signal intensity (SI) curves were obtained from the linear average of SIs in intratumoral and matched-depth renal cortex regions of interest. A kinetic parameter calculated from reperfusion curves reflects local perfusion, normalized with respect to adjacent renal cortex perfusion. Normalized perfusion obtained from each group was compared with that from the other groups and with necrosis percentages and microvascular density assessed histologically at day 35. Comparisons were made by using analyses of variance and Tukey-Kramer tests. RESULTS: The lowest excised mean tumor weights (+/- standard deviation) corresponded to the longest bevacizumab-treatment duration: 1.4 g +/- 1.1 (continuous-treatment) compared with 2.3 g +/- 2.1 (discontinued) and 3.7 g +/- 1.9 (control) (P = .01). On day 35, the respective control and continuously treated groups had comparable and significantly larger necrotic areas: 37% +/- 14 and 32% +/- 17 larger than the discontinued-treatment group (15% +/- 9; P < .05). Normalized perfusion increased significantly with time (P = .02) in the discontinued-treatment group after therapy ceased (day 22). CONCLUSION: Noninvasively measured contrast-enhanced US parameters demonstrated tumor revascularization after stopping antiangiogenic therapy in this murine tumor model.

Mapping of transrectal ultrasonographic prostate biopsies: quality control and learning curve assessment by image processing.

OBJECTIVE: Mapping of transrectal ultrasonographic (TRUS) prostate biopsies is of fundamental importance for either diagnostic purposes or the management and treatment of prostate cancer, but the localization of the cores seems inaccurate. Our objective was to evaluate the capacities of an operator to plan transrectal prostate biopsies under 2-dimensional TRUS guidance using a registration algorithm to represent the localization of biopsies in a reference 3-dimensional ultrasonographic volume. METHODS: Thirty-two patients underwent a series of 12 prostate biopsies under local anesthesia performed by 1 operator using a TRUS probe combined with specific third-party software to verify that the biopsies were indeed conducted within the planned targets. RESULTS: The operator reached 71% of the planned targets with substantial variability that depended on their localization (100% success rate for targets in the middle and right parasagittal parts versus 53% for targets in the left lateral base). Feedback from this system after each series of biopsies enabled the operator to significantly improve his dexterity over the course of time (first 16 patients: median score, 7 of 10 and cumulated median biopsy length in targets of 90 mm; last 16 patients, median score, 9 of 10 and a cumulated median length of 121 mm; P = .046). CONCLUSIONS: In addition to being a useful tool to improve the distribution of prostate biopsies, the potential of this system is above all the preparation of a detailed "map" of each patient showing biopsy zones without substantial changes in routine clinical practices.