Central Adiposity Increases Risk of Kidney Stone Disease through Effects on Serum Calcium Concentrations.

SIGNIFICANCE STATEMENT: Kidney stone disease is a common disorder with poorly understood pathophysiology. Observational and genetic studies indicate that adiposity is associated with an increased risk of kidney stone disease. However, the relative contribution of general and central adipose depots and the mechanisms by which effects of adiposity on kidney stone disease are mediated have not been defined. Using conventional and genetic epidemiological techniques, we demonstrate that general and central adiposity are independently associated with kidney stone disease. In addition, one mechanism by which central adiposity increases risk of kidney stone disease is by increasing serum calcium concentration. Therapies targeting adipose depots may affect calcium homeostasis and help to prevent kidney stone disease. BACKGROUND: Kidney stone disease affects approximately 10% of individuals in their lifetime and is frequently recurrent. The disease is linked to obesity, but the mechanisms mediating this association are uncertain. METHODS: Associations of adiposity and incident kidney stone disease were assessed in the UK Biobank over a mean of 11.6 years/person. Genome-wide association studies and Mendelian randomization (MR) analyses were undertaken in the UK Biobank, FinnGen, and in meta-analyzed cohorts to identify factors that affect kidney stone disease risk. RESULTS: Observational analyses on UK Biobank data demonstrated that increasing central and general adiposity is independently associated with incident kidney stone formation. Multivariable MR, using meta-analyzed UK Biobank and FinnGen data, established that risk of kidney stone disease increases by approximately 21% per one standard deviation increase in body mass index (BMI, a marker of general adiposity) independent of waist-to-hip ratio (WHR, a marker of central adiposity) and approximately 24% per one standard deviation increase of WHR independent of BMI. Genetic analyses indicate that higher WHR, but not higher BMI, increases risk of kidney stone disease by elevating adjusted serum calcium concentrations (ß=0.12 mmol/L); WHR mediates 12%-15% of its effect on kidney stone risk in this way. CONCLUSIONS: Our study indicates that visceral adipose depots elevate serum calcium concentrations, resulting in increased risk of kidney stone disease. These findings highlight the importance of weight loss in individuals with recurrent kidney stones and suggest that therapies targeting adipose depots may affect calcium homeostasis and contribute to prevention of kidney stone disease.

Impact of COVID-19 on the management and outcomes of ureteric stones in the UK: a multicentre retrospective study.

OBJECTIVES: To determine if management of ureteric stones in the UK changed during the coronavirus disease 2019 (COVID-19) pandemic and whether this affected patient outcomes. PATIENTS AND METHODS: We conducted a multicentre retrospective study of adults with computed tomography-confirmed ureteric stone disease at 39 UK hospitals during a pre-pandemic period (23/3/2019-22/6/2019) and a period during the pandemic (the 3-month period after the first severe acute respiratory syndrome coronavirus-2 case at individual sites). The primary outcome was success of primary treatment modality, defined as no further treatment required for the index ureteric stone. Our study protocol was published prior to data collection. RESULTS: A total of 3735 patients were included (pre-pandemic 1956 patients; pandemic 1779 patients). Stone size was similar between groups (P > 0.05). During the pandemic, patients had lower hospital admission rates (pre-pandemic 54.0% vs pandemic 46.5%, P < 0.001), shorter mean length of stay (4.1 vs 3.3 days, P = 0.02), and higher rates of use of medical expulsive therapy (17.4% vs 25.4%, P < 0.001). In patients who received interventional management (pre-pandemic 787 vs pandemic 685), rates of extracorporeal shockwave lithotripsy (22.7% vs 34.1%, P < 0.001) and nephrostomy were higher (7.1% vs 10.5%, P = 0.03); and rates of ureteroscopy (57.2% vs 47.5%, P < 0.001), stent insertion (68.4% vs 54.6%, P < 0.001), and general anaesthetic (92.2% vs 76.2%, P < 0.001) were lower. There was no difference in success of primary treatment modality between patient cohorts (pre-pandemic 73.8% vs pandemic 76.1%, P = 0.11), nor when patients were stratified by treatment modality or stone size. Rates of operative complications, 30-day mortality, and re-admission and renal function at 6 months did not differ between the data collection periods. CONCLUSIONS: During the COVID-19 pandemic, there were lower admission rates and fewer invasive procedures performed. Despite this, there were no differences in treatment success or outcomes. Our findings indicate that clinicians can safely adopt management strategies developed during the pandemic to treat more patients conservatively and in the community.

Natural history of small asymptomatic kidney and residual stones over a long-term follow-up: systematic review over 25 years.

OBJECTIVE: To systematically review the natural history of small asymptomatic kidney and residual stones, as the incidental identification of small, asymptomatic renal calculi has risen with increasing use of high-resolution imaging. MATERIALS AND METHODS: We reviewed the natural history of small asymptomatic kidney and residual stones using the Cochrane and Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) methodology. We searched MEDLINE, Scopus, EMBASE, EBSCO, Cochrane library and Clinicaltrials.gov using themes of 'asymptomatic', 'nephrolithiasis', 'observation', 'symptoms', 'admission', 'intervention' and similar allied terms for all English language articles from 1996 to 2020 (25 years). Inclusion criteria were studies with ≥50 patients, stones ≤10 mm, and a mean follow-up of ≥24 months. Primary outcomes were occurrence of symptoms, emergency admission, and interventions. RESULTS: Our literature search returned 2247 results of which 10 papers were included in the final review. Risk of symptomatic episodes ranged from 0% to 59.4%. Meta-analysis did not identify any significant difference in the likelihood of developing symptoms when comparing stones <5 mm to those >5 mm, nor those <10 mm to those >10 mm. Risk of admission varied from 14% to 19% and the risk of intervention from 12% to 35%. Meta-analysis showed a significantly decreased likelihood of intervention for stones <5 vs >5 mm and <10 vs >10 mm. Studies had variable risk of bias due to heterogeneous reporting of outcome measures with significant likelihood that observed differences in results were compatible with chance alone (Symptoms: I2 =0%, Cochran's Q = 3.09, P = 0.69; Intervention: I2 =0%, Cochran's Q = 1.76, P = 0.88). CONCLUSIONS: The present systematic review indicates that stone size is not a reliable predictor of symptoms; however, risk of intervention is greater for stones >5mm vs <5 mm and >10 vs <10 mm. This review will inform urologists as they discuss management strategies with patients who have asymptomatic renal stones and offer insight to committees during the development of evidence-based guidelines.

The New Lithotripsy Index predicts success of shock wave lithotripsy.

AIM: The aim of this study is to evaluate the factors affecting treatment success in patients who underwent Shock wave lithotripsy (SWL) and to investigate the effect of the Storz Medical Lithotripsy Index (SMLI) on treatment effectiveness. METHODS: Prospective data were collected on patients undergoing SWL treatment for kidney stones between January 2013 and May 2021. Stone location, number and size were determined with non-contrast CT (NCCT) for all patients. All patients underwent SWL with a Storz Modulith SLK lithotripsy machine without anaesthesia. The total amount of energy applied to the stone was calculated using the SMLI. All patients were evaluated for stone-free status by X-ray at least 2 weeks after treatment. The success of the procedure was defined as the patient being completely stone free or the detection of residual fragments < 4 mm that did not require further treatment. RESULTS: A total of 1230 patients with kidney stones were included in the study. The mean age of the patients was 42.33 ± 11.78 (18-75), and the mean BMI was 28.47 ± 8.78 (19.25-38.52). During SWL, 75.6% of patients demonstrated excellent pain tolerance (930/1230). A total of 116 patients could not tolerate the pain during SWL (9.4%). Treatment success was associated with fewer treatment sessions (2.34 ± 1.75 vs. 2.90 ± 2.04; p < 0.001), smaller stone size (7.52 ± 3.29 vs 8.60 ± 3.93; p < 0.001) and higher SMLI/stone size (25.11 ± 13.63 vs. 22.27 ± 14.50; p < 0.001). In the univariate and multivariate regression analysis, the factors affecting the success of the treatment were the number of sessions (OR 1.170), stone size (OR 1.142), number of shocks (OR 1.005), SMLI/stone size (OR 1.024) and pain tolerance (OR 0.692). CONCLUSION: In the treatment of kidney stones with SWL, stone site, stone size, SMLI/stone size, and pain tolerance are the factors affecting success. SMLI per stone size is a statistically significant factor for predicting SWL success.

Natural History of Post-Treatment Kidney Stone Fragments: A Systematic Review and Meta-Analysis.

PURPOSE: We assessed the literature around post-treatment asymptomatic residual stone fragments and performed a meta-analysis. The main outcomes were intervention rate and disease progression. MATERIALS AND METHODS: We searched Ovid®, MEDLINE®, Embase™, the Cochrane Library and ClinicalTrials.gov using search terms: "asymptomatic", "nephrolithiasis", "ESWL", "PCNL", "URS" and "intervention." Inclusion criteria were all studies with residual renal fragments following treatment (shock wave lithotripsy, ureteroscopy or percutaneous nephrolithotomy). Analysis was performed using 'metafor' in R and bias determined using Newcastle-Ottawa scale. RESULTS: From 273 articles, 18 papers (2,096 patients) had details of intervention rate for residual fragments. Aggregate intervention rates for ≤4 mm fragments rose from 19% (20 months) to 22% (50 months), while >4 mm fragments rose from 22% to 47%. Aggregate disease progression rates for ≤4 mm rose from 25% to 47% and >4 mm rose from 26% to 88%. However, there was substantial difference in definition of "disease progression." Meta-analysis comparing >4 mm against ≤4 mm fragments: intervention rate for >4 mm (vs ≤4 mm): OR=1.50 (95% CI 0.70-2.30), p <0.001, I2=67.6%, tau2=0.48, Cochran's Q=11.4 (p=0.02) and Egger's regression: z=3.11, p=0.002. Disease progression rate for >4 mm: OR=0.06 (95% CI -0.98-1.10), p=0.91, I2=53.0%, tau2=0.57, Cochran's Q=7.11 (p=0.07) and Egger's regression: z=-0.75, p=0.45. Bias analysis demonstrated a moderate risk. CONCLUSIONS: Larger post-treatment residual fragments are significantly more likely to require further intervention especially in the long term. Smaller fragments, although less likely to require further intervention, still carry that risk. Notably, there is no significant difference in disease progression between fragment sizes. Patients with residual fragments should be appropriately counselled and informed decision-making regarding further management should be done.

Local anaesthetic transperineal (LATP) prostate biopsy using a probe-mounted transperineal access system: a multicentre prospective outcome analysis.

OBJECTIVES: To assess the feasibility of local anaesthetic transperineal (LATP) technique using a single-freehand transperineal (TP) access device, and report initial prostate cancer (PCa) detection, infection rates, and tolerability. PATIENTS AND METHODS: Observational study of a multicentre prospective cohort, including all consecutive cases. LATP was performed in three settings: (i) first biopsy in suspected PCa, (ii) confirmatory biopsies for active surveillance, and (iii) repeat biopsy in suspected PCa. All patients received pre-procedure antibiotics according to local hospital guidelines. Local anaesthesia was achieved by perineal skin infiltration and periprostatic nerve block without sedation. Ginsburg protocol principles were followed for systematic biopsies including cognitive magnetic resonance imaging-targeted biopsies when needed using the PrecisionPoint™ TP access device. Procedure-related complications and oncological outcomes were prospectively and consecutively collected. A validated questionnaire was used in a subset of centres to collect data on patient-reported outcome measures (PROMs). RESULTS: Some 1218 patients underwent LATP biopsies at 10 centres: 55%, 24%, and 21% for each of the three settings, respectively. Any grade PCa was diagnosed in 816 patients (67%), of which 634 (52% of total) had clinically significant disease. Two cases of sepsis were documented (0.16%) and urinary retention was observed in 19 patients (1.6%). PROMs were distributed to 419 patients, with a 56% response rate (n = 234). In these men, pain during the biopsy was described as either 'not at all' or 'a little' painful by 64% of patients. Haematuria was the most common reported symptom (77%). When exploring attitude to re-biopsy, 48% said it would be 'not a problem' and in contrast 8.1% would consider it a 'major problem'. Most of the patients (81%) described the biopsy as a 'minor or moderate procedure tolerable under local anaesthesia', while 5.6% perceived it as a 'major procedure that requires general anaesthesia'. CONCLUSION: Our data suggest that LATP biopsy using a TP access system mounted to the ultrasound probe achieves excellent PCa detection, with a very low sepsis rate, and is safe and well tolerated. We believe a randomised controlled trial comparing LATP with transrectal ultrasound-guided biopsy (TRUS) to investigate the relative trade-offs between each biopsy technique would be helpful.

Comparison of Transrectal Ultrasound Biopsy to Transperineal Template Mapping Biopsies Stratified by Multiparametric Magnetic Resonance Imaging Score in the PROMIS Trial.

PURPOSE: We evaluated the performance of transrectal ultrasound guided systematic and transperineal template mapping biopsies with a 5 mm sampling frame stratified by the multiparametric magnetic resonance imaging Likert score in the PROMIS (Prostate MR Imaging Study). MATERIALS AND METHODS: Biopsy naïve men due to undergo prostate biopsy for elevated prostate specific antigen and/or abnormal digital rectal examination underwent multiparametric magnetic resonance imaging, and transperineal template mapping and transrectal ultrasound guided systematic biopsies, which were performed and reported while blinded to other test results. Clinically significant prostate cancer was primarily defined as Gleason 4 + 3 or greater, or a maximum cancer core length of 6 mm or more of any grade. It was secondarily defined as Gleason 3 + 4 or greater, or a maximum cancer core length of 4 mm or more of any grade. RESULTS: In 41 months 740 men were recruited at a total of 11 centers, of whom 576 underwent all 3 tests. Eight of the 150 men (5.1%) with a multiparametric magnetic resonance imaging score of 1-2 had any Gleason 3 + 4 or greater disease on transrectal ultrasound guided systematic biopsy. Of the 75 men in whom transrectal ultrasound guided systematic biopsy showed Gleason 3 + 3 of any maximum cancer core length 61 (81%) had Gleason 3 + 4, 8 (11%) had Gleason 4 + 3 and 0 (0%) had Gleason 4 + 5 or greater disease. For definition 1 (clinically significant prostate cancer) transrectal ultrasound guided systematic biopsy sensitivity remained stable and low across multiparametric magnetic resonance imaging Likert scores of 35% to 52%. For definition 2 (clinically significant prostate cancer and any cancer) sensitivity increased with higher multiparametric magnetic resonance imaging scores. The negative predictive value varied due to varying disease prevalence but for all cancer thresholds it declined with increasing multiparametric magnetic resonance imaging scores. CONCLUSIONS: In the setting of multiparametric magnetic resonance imaging Likert scores 1-2 transrectal ultrasound guided systematic biopsy revealed Gleason 3 + 4 disease in only 1 of 20 men. Further, for any clinically significant prostate cancer definition transrectal ultrasound guided systematic biopsy had poor sensitivity and variable but a low negative predictive value across multiparametric magnetic resonance imaging scores. Men who undergo transrectal ultrasound guided systematic biopsy without targeting in the setting of a multiparametric magnetic resonance imaging score of 3 to 5 should be advised to undergo repeat (targeted) biopsy.

Evaluation of functional outcomes after a second focal high-intensity focused ultrasonography (HIFU) procedure in men with primary localized, non-metastatic prostate cancer: results from the HIFU Evaluation and Assessment of Treatment (HEAT) registry.

OBJECTIVES: To assess change in functional outcomes after a second focal high-intensity focused ultrasonography (HIFU) treatment compared with outcomes after one focal HIFU treatment. PATIENTS AND METHODS: In this multicentre study (2005-2016), 821 men underwent focal HIFU for localized non-metastatic prostate cancer. The patient-reported outcome measures of International Prostate Symptom Score (IPSS), pad usage and erectile function (EF) score were prospectively collected for up to 3 years. To be included in the study, completion of at least one follow-up questionnaire was required. The primary outcome was comparison of change in functional outcomes between baseline and follow-up after one focal HIFU procedure vs after a second focal HIFU procedure, using IPSS, Expanded Prostate Cancer Index Composite (EPIC) and International Index of Erectile Function (IIEF) questionnaires. RESULTS: Of 821 men, 654 underwent one focal HIFU procedure and 167 underwent a second focal HIFU procedure. A total of 355 (54.3%) men undergoing one focal HIFU procedure and 65 (38.9%) with a second focal HIFU procedure returned follow-up questionnaires, respectively. The mean age and prostate-specific antigen level were 66.4 and 65.6 years, and 7.9 and 8.4 ng/mL, respectively. After one focal HIFU treatment, the mean change in IPSS was -0.03 (P = 0.02) and in IIEF (EF score) it was -0.4 (P = 0.02) at 1-2 years, with no subsequent decline. Absolute rates of erectile dysfunction increased from 9.9% to 20.8% (P = 0.08), leak-free continence decreased from 77.9% to 72.8% (P = 0.06) and pad-free continence from 98.6% to 94.8% (P = 0.07) at 1-2 years, respectively. IPSS prior to second focal HIFU treatment compared to baseline IPSS prior to first focal HIFU treatment was lower by -1.3 (P = 0.02), but mean IPSS change was +1.4 at 1-2 years (P = 0.03) and +1.2 at 2-3 years (P = 0.003) after the second focal HIFU treatment. The mean change in EF score after the second focal HIFU treatment was -0.2 at 1-2 years (P = 0.60) and -0.5 at 2-3 years (P = 0.10), with 17.8% and 6.2% of men with new erectile dysfunction. The rate of new pad use was 1.8% at 1-2 years and 2.6% at 2-3 years. CONCLUSION: A second focal HIFU procedure causes minor detrimental effects on urinary function and EF. These data can be used to counsel patients with non-metastatic prostate cancer prior to considering HIFU therapy.

Defining a national reference level for intraoperative radiation exposure in urological procedures: FLASH, a retrospective multicentre UK study.

OBJECTIVES: To define reference levels for intraoperative radiation during stent insertion, ureteroscopy (URS), and percutaneous nephrolithotomy (PCNL); to identify variation in radiation exposure between individual hospitals across the UK, between low- and high-volume PCNL centres, and between grade of lead surgeon. PATIENTS/SUBJECTS AND METHODS: In all, 3651 patients were identified retrospectively across 12 UK hospitals over a 1-year period. Radiation exposure was defined in terms of total fluoroscopy time (FT) and dose area product (DAP). The 75th percentiles of median values for each hospital were used to define reference levels for each procedure. RESULTS: Reference levels: ureteric stent insertion/replacement (DAP, 2.3 Gy/cm2 ; FT, 49 s); URS (DAP, 2.8 Gy/cm2 ; FT, 57 s); PCNL (DAP, 24.1 Gy/cm2 ; FT, 431 s). Significant variations in the median DAP and FT were identified between individual centres for all procedures (P < 0.001). For PCNL, there was a statistically significant difference between DAP for low- (<50 cases/annum) and high-volume centres (>50 cases/annum), at a median DAP of 15.0 Gy/cm2 vs 4.2 Gy/cm2 (P < 0.001). For stent procedures, the median DAP and FT differed significantly between grade of lead surgeon: Consultant (DAP, 2.17 Gy/cm2 ; FT, 41 s) vs Registrar (DAP, 1.38 Gy/cm2 ; FT, 26 s; P < 0.001). CONCLUSION: This multicentre study is the largest of its kind. It provides the first national reference level to guide fluoroscopy use in urological procedures, thereby adding a quantitative and objective value to complement the principles of keeping radiation exposure 'as low as reasonably achievable'. This snapshot of real-time data shows significant variation around the country, as well as significant differences between low- and high-volume centres for PCNL, and grade of lead surgeon for stent procedures.

Development of a standardised training curriculum for robotic surgery: a consensus statement from an international multidisciplinary group of experts.

OBJECTIVES: To explore the views of experts about the development and validation of a robotic surgery training curriculum, and how this should be implemented. MATERIALS AND METHODS: An international expert panel was invited to a structured session for discussion. The study was of a mixed design, including qualitative and quantitative components based on focus group interviews during the European Association of Urology (EAU) Robotic Urology Section (ERUS) (2012), EAU (2013) and ERUS (2013) meetings. After introduction to the aims, principles and current status of the curriculum development, group responses were elicited. After content analysis of recorded interviews generated themes were discussed at the second meeting, where consensus was achieved on each theme. This discussion also underwent content analysis, and was used to draft a curriculum proposal. At the third meeting, a quantitative questionnaire about this curriculum was disseminated to attendees to assess the level of agreement with the key points. RESULTS: In all, 150 min (19 pages) of the focus group discussion was transcribed (21 316 words). Themes were agreed by two raters (median agreement κ 0.89) and they included: need for a training curriculum (inter-rater agreement κ 0.85); identification of learning needs (κ 0.83); development of the curriculum contents (κ 0.81); an overview of available curricula (κ 0.79); settings for robotic surgery training ((κ 0.89); assessment and training of trainers (κ 0.92); requirements for certification and patient safety (κ 0.83); and need for a universally standardised curriculum (κ 0.78). A training curriculum was proposed based on the above discussions. CONCLUSION: This group proposes a multi-step curriculum for robotic training. Studies are in process to validate the effectiveness of the curriculum and to assess transfer of skills to the operating room.

The "Is mpMRI Enough" or IMRIE Study: A Multicentre Evaluation of Prebiopsy Multiparametric Magnetic Resonance Imaging Compared with Biopsy.

BACKGROUND: Multiparametric magnetic resonance imaging (mpMRI) is now recommended prebiopsy in numerous healthcare regions based on the findings of high-quality studies from expert centres. Concern remains about reproducibility of mpMRI to rule out clinically significant prostate cancer (csPCa) in real-world settings. OBJECTIVE: To assess the diagnostic performance of mpMRI for csPCa in a real-world setting. DESIGN, SETTING, AND PARTICIPANTS: A multicentre, retrospective cohort study, including men referred with raised prostate-specific antigen (PSA) or an abnormal digital rectal examination who had undergone mpMRI followed by transrectal or transperineal biopsy, was conducted. Patients could be biopsy naïve or have had previous negative biopsies. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary definition for csPCa was International Society of Urological Pathology (ISUP) grade group (GG) ≥2 (any Gleason ≥7); the accuracy for other definitions was also evaluated. RESULTS AND LIMITATIONS: Across ten sites, 2642 men were included (January 2011-November 2018). Mean age and PSA were 65.3yr (standard deviation [SD] 7.8yr) and 7.5ng/ml (SD 3.3ng/ml), respectively. Of the patients, 35.9% had "negative MRI" (scores 1-2); 51.9% underwent transrectal biopsy and 48.1% had transperineal biopsy, with 43.4% diagnosed with csPCa overall. The sensitivity and negative predictive value (NPV) for ISUP GG≥2 were 87.3% and 87.5%, respectively. The NPVs were 87.4% and 88.1% for men undergoing transrectal and transperineal biopsy, respectively. Specificity and positive predictive value of MRI were 49.8% and 49.2%, respectively. The sensitivity and NPV increased to 96.6% and 90.6%, respectively, when a PSA density threshold of 0.15ng/ml/ml was used in MRI scores 1-2; these metrics increased to 97.5% and 91.2%, respectively, for PSA density 0.12ng/ml/ml. ISUP GG≥3 (Gleason ≥4+3) was found in 2.4% (15/617) of men with MRI scores 1-2. They key limitations of this study are the heterogeneity and retrospective nature of the data. CONCLUSIONS: Multiparametric MRI when used in real-world settings is able to rule out csPCa accurately, suggesting that about one-third of men might avoid an immediate biopsy. Men should be counselled about the risk of missing some significant cancers. PATIENT SUMMARY: Multiparametric magnetic resonance imaging (MRI) is a useful tool for ruling out prostate cancer, especially when combined with prostate-specific antigen density (PSAD). Previous results published from specialist centres can be reproduced at smaller institutions. However, patients and their clinicians must be aware that an early diagnosis of clinically significant prostate cancer could be missed in nearly 10% of patients by relying on MRI and PSAD alone.

Sexual function outcomes following interventions for prostate cancer: are contemporary reports on functional outcomes misleading?

Patients with primary localised prostate cancer (PCa) have a wide choice of curative therapeutic interventions, including active surveillance, surgical, focal and radiation therapies. Based on clinical and oncological characteristics, treatment decisions entail consideration of oncological and functional outcomes with important effects on quality of life. We aimed to highlight evidence surrounding present inconsistencies, the problems this presents to clinicians and patients alike and the rationale for using return to baseline as a more realistic and objective functional outcome measure for assessing sexual function in this particularly sensitive group of men. We performed a non-systematic literature review of numerous non-validated, arbitrary thresholds employed in evaluation of sexual function outcomes in men undergoing intervention for primary localised PCa. The literature presents much heterogeneity in measurement methods and outcome measures, which lack context and present difficulties when counselling patients to make informed, autonomous decisions. These include findings from the most widely used internationally validated tools, such as the International Index of Erectile Function (IIEF), UCLA prostate cancer index and European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 (QLQ-C30). There is a need for standardisation of reporting outcomes following PCa treatment to facilitate evaluation of existing and emerging technologies.

A prospective analysis of robotic targeted MRI-US fusion prostate biopsy using the centroid targeting approach.

Robotic prostate biopsy is an emerging technology. Recent development of this tool has allowed the performance of a transperineal prostate biopsy allowing pre-programmed standardized biopsy schemes. Prospective data collection was undertaken in 86 consecutive men who underwent robotically assisted transperineal prostate biopsy. All underwent a multi-parametric MRI pre-biopsy with centroid targeting followed by systematic template prostate biopsy. For the purposes of this study, our definition of clinically significant prostate cancer (csPCa) is any Gleason score > 6. Mean (SD) age, median (IQR) PSA, and median (IQR) prostate volume were 64.24 (6.97) years, of 7.79 ng/ml (6.5) and 45.06 cc (28), respectively. Overall, 44 (51.2%) men were diagnosed with csPCa. csPCa was detected in the targeted biopsies alone in 35 (40.1%) men. The addition of the 12-zone template biopsy increased the yield of csPCa for another 9 (10.5%) men. Of these 9 men, the majority (7) harbored primary pattern 3 disease and only 1 was identified to have high-grade disease. Out of these 9 men, 7 of them had the identification of csPCa in the sector, where a target was contained within that zone. Robotic-assisted prostate biopsy in our study has demonstrated a high detection of csPCa when combined with limited near-field sampling. Our study suggests the use of more accurate biopsy schemes such as ring-targeting of lesions to mitigate against systematic and random mathematical errors. Adoption of this tool and biopsy strategy would potentially avoid the increased morbidity associated with whole gland systematic unguided biopsies.

Prostate imaging features that indicate benign or malignant pathology on biopsy.

Accurate diagnosis of clinically significant prostate cancer is essential in identifying patients who should be offered treatment with curative intent. Modifications to the Gleason grading system in recent years show that accurate grading and reporting at needle biopsy can improve identification of clinically significant prostate cancers. Extracapsular extension of prostate cancer has been demonstrated to be an adverse prognostic factor with greater risk of metastatic spread than organ-confined disease. Tumor volume may be an independent prognostic factor and should be considered in conjunction with other factors. Multi-parametric magnetic resonance imaging (MP-MRI) has become an increasingly important tool in the diagnosis and characterization of prostate cancer. MP-MRI allows T2-weighted (T2W) anatomical imaging to be combined with functional and physiological assessment. Diffusion-weighted imaging (DWI) has shown greater sensitivity, specificity and negative predictive value compared to prostate specific antigen (PSA) testing and T2W imaging alone and has a more positive correlation with Gleason score and tumour volume. Dynamic gadolinium contrast-enhanced (DCE) imaging can exhibit difficulties in distinguishing prostatitis from malignancy in the peripheral zone, and between benign prostatic hyperplasia (BPH) and malignancies in the transition zone (TZ). Computer aided diagnosis utilizes software to aid radiologists in detecting and diagnosing abnormalities from diagnostic imaging. New techniques of quantitative MRI, such as VERDICT MRI use tissue-specific factors to delineate different cellular and microstructural phenotypes, characterizing tissue properties with greater detail. Proton MR spectroscopic imaging (MRSI) is a more technically challenging imaging modality than DCE and DWI MRI. Over the last decade, choline and prostate-specific membrane antigen (PSMA) positron emission tomography (PET) have developed as better tools for staging than conventional imaging. While hyperpolarized MRI shows promise in improving the imaging and differentiation of benign and malignant lesions there is further work required. Accurate reading and interpretation of diagnostic investigations is key to accurate identification of abnormal areas requiring biopsy, sparing those in whom benign or indolent disease can be managed by non-invasive means. Embracing and advancing existing technologies is essential in furthering this process.

Training Modalities in Robot-assisted Urologic Surgery: A Systematic Review.

CONTEXT: Novel surgical techniques demand that surgical training adapts to the need for technical and nontechnical skills. OBJECTIVE: To identify training methods available for robot-assisted surgical (RAS) training in urology, evaluate their effectiveness in terms of validation, educational impact, acceptability, and cost effectiveness, and assess their effect on learning curves (LCs). EVIDENCE ACQUISITION: A systematic review following Preferred Reporting Items for Systematic Reviews and Meta-analysis guidelines searched Ovid Medline, Embase, PsycINFO, and the Cochrane Library. Results were screened to include appropriate studies. Quality was evaluated. Each method was evaluated, and conclusions were drawn regarding LCs. EVIDENCE SYNTHESIS: Of 359 records, 24 were included (521 participants). Training methods included dry-lab training (n=7), wet-lab training (n=7), mentored training (n=7), and nonstructured pathways (n=5). Dry-lab training demonstrated educational impact by reducing console time and was acceptable in a study; 100% of participants confirmed face validity. Wet-lab training principally uses human cadaveric material; effectiveness is well rated, although dry-lab training and observation were rated as equally useful. Mentored programmes combine lectures, tutorials, observation, simulation, and proctoring. Minifellowships were linked to greater practice of RAS 1 yr later. LCs vary according to experience. One study found that surgeons from robot-related fellowships demonstrated fewer positive surgical margins than surgeons from laparoscopic-related fellowships (24% vs 34.6%; p=0.05) and reduced time (132 vs 152min; p=0.0003). Five studies examined nonstructured training pathways (clinical practice). Experience correlated with fewer complications (p=0.007), improved continence (p=0.049), and reduced time (p=0.002). CONCLUSIONS: RAS training methods include dry and wet lab, mentored training, and nonstructured pathways. Limited available evidence suggests that they affect LCs differently and are rarely used alone. The different methods of training appear effective when combined. Their benefits must be explored to facilitate validated acceptable training with educational impact. PATIENT SUMMARY: Robot-assisted training encompasses several methods used in combination, but more evidence is required to gain the greatest benefit and formulate future training pathways.

Simulation training in upper tract endourology: myth or reality?

Surgeons training in the twenty-first century are subject to a myriad of pressures, as has always been the case within surgical training. These include reduced hours available for training and increased threat of litigation against their operating practice. The Halstedian approach of "see one, do one, teach one" has been replaced within surgical training and simulation has become established to enable urology trainees to develop technical and non-technical skills away from the operating room. With the primary focus as patient safety and increasing operating skill, "simulation training" encompasses several modalities. These include wet-lab cadaveric and animal models, dry lab, high fidelity, low-fidelity and virtual reality (VR). These can be used to practice generic surgical skills, such as laparoscopic suturing or knot tying on a robotic console. Beyond this there is potential for simulation training courses and full-immersion simulation to address non-technical skills and team aspects within the operating room. To incorporate simulators into training, models must be carefully designed and evaluated according to certain considerations, ensuring that they address parameters such as face, content and construct validity. This review aimed to provide an overview of simulation platforms available within endourology, considering ureterorenoscopy and percutaneous nephrolithotomy and the status of their validation.

Modular Training for Robot-Assisted Radical Prostatectomy: Where to Begin?

OBJECTIVE: Effective training is paramount for patient safety. Modular training entails advancing through surgical steps of increasing difficulty. This study aimed to construct a modular training pathway for use in robot-assisted radical prostatectomy (RARP). It aims to identify the sequence of procedural steps that are learnt before surgeons are able to perform a full procedure without an intervention from mentor. DESIGN: This is a multi-institutional, prospective, observational, longitudinal study. We used a validated training tool (RARP Score). Data regarding surgeons' stage of training and progress were collected for analysis. A modular training pathway was constructed with consensus on the level of difficulty and evaluation of individual steps. We identified and recorded the sequence of steps performed by fellows during their learning curves. SETTING AND PARTICIPANTS: We included 15 urology fellows from UK, Europe, and Australia. RESULTS: A total of 15 surgeons were assessed by mentors in 425 RARP cases over 8 months (range: 7-79) across 15 international centers. There were substantial differences in the sequence of RARP steps according to the chronology of the procedure, difficulty level, and the order in which surgeons actually learned steps. Steps were not attempted in chronological order. The greater the difficulty, the later the cohort first undertook the step (p = 0.021). The cohort undertook steps of difficulty level I at median case number 1. Steps of difficulty levels II, III, and IV showed more variation in median case number of the first attempt. We recommend that, in the operating theater, steps be learned in order of increasing difficulty. A new modular training route has been designed. This incorporates the steps of RARP with the following order of priority: difficulty level > median case number of first attempt > most frequently undertaken in surgical training. CONCLUSIONS: An evidence-based modular training pathway has been developed that facilitates a safe introduction to RARP for novice surgeons.

Structured and Modular Training Pathway for Robot-assisted Radical Prostatectomy (RARP): Validation of the RARP Assessment Score and Learning Curve Assessment.

BACKGROUND: Use of robot-assisted radical prostatectomy (RARP) for prostate cancer is increasing. Structured surgical training and objective assessment are critical for outcomes. OBJECTIVE: To develop and validate a modular training and assessment pathway via Healthcare Failure Mode and Effect Analysis (HFMEA) for trainees undertaking RARP and evaluate learning curves (LCs) for procedural steps. DESIGN, SETTING, AND PARTICIPANTS: This multi-institutional (Europe, Australia, and United States) observational prospective study used HFMEA to identify the high-risk steps of RARP. A specialist focus group enabled validation. Fifteen trainees who underwent European Association of Urology robotic surgery curriculum training performed RARP and were assessed by mentors using the tool developed. Results produced LCs for each step. A plateau above score 4 indicated competence. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: We used a modular training and assessment tool (RARP Assessment Score) to evaluate technical skills. LCs were constructed. Multivariable Kruskal-Wallis, Mann-Whitney U, and κ coefficient analyses were used. RESULTS AND LIMITATIONS: Five surgeons were observed for 42 console hours to map steps of RARP. HFMEA identified 84 failure modes and 46 potential causes with a hazard score ≥8. Content validation created the RARP Assessment Score: 17 stages and 41 steps. The RARP Assessment Score was acceptable (56.67%), feasible (96.67%), and had educational impact (100%). Fifteen robotic surgery trainees were assessed for 8 mo. In 426 RARP cases (range: 4-79), all procedural steps were attempted by trainees. Trainees were assessed with the RARP Assessment Score by their expert mentors, and LCs for individual steps were plotted. LCs demonstrated plateaus for anterior bladder neck transection (16 cases), posterior bladder neck transection (18 cases), posterior dissection (9 cases), dissection of prostatic pedicle and seminal vesicles (15 cases), and anastomosis (17 cases). Other steps did not plateau during data collection. CONCLUSIONS: The RARP Assessment Score based on HFMEA methodology identified critical steps for focused RARP training and assessed surgeons. LCs demonstrate the experience necessary to reach a level of competence in technical skills to protect patients. PATIENT SUMMARY: We developed a safety and assessment tool to gauge the technical skills of surgeons performing robot-assisted radical prostatectomy. Improvement was monitored, and measures of progress can be used in future to guide mentors when training surgeons to operate safely.