Whole-exome sequencing reveals a comprehensive germline mutation landscape and identifies twelve novel predisposition genes in Chinese prostate cancer patients.

Prostate cancer is the most inheritable cancer with approximately 42% of disease risk attributed to inherited factors by studies of twins, indicating the importance of additional genetic screening to identify predisposition variants. However, only DNA damage repair (DDR) genes have been investigated thoroughly in prostate cancer. To determine the comprehensive germline mutation landscape in Chinese prostate cancer patients, we performed whole exome sequencing in 100 Han Chinese patients with prostate cancer in Hong Kong and identified deleterious germline mutations. A total of 36 deleterious germline variants in 25 genes were identified in 29% patients. Variants were found in eight pathways, including DNA methylation, DDR, and tyrosine-protein kinase. These findings were validated in an independent Chinese cohort of 167 patients with prostate cancer in Shanghai. Seven common deleterious-variant-containing genes were found in discovery cohort (7/25, 28%) and validation cohort (7/28, 25%) with three genes not described before (LDLR, MYH7 and SUGCT) and four genes previously reported (FANCI, ITGA6, PABPC1 and RAD54B). When comparing with that of a cohort of East Asian healthy individuals, 12 non-DDR novel potential predisposition genes (ADGRG1, CHD4, DNMT3A, ERBB3, GRHL1, HMBS, LDLR, MYH7, MYO6, NT5C2, NUP98 and SUGCT) were identified using the discovery and validation cohorts, which have not been previously reported in prostate cancer patients in all ethnic groups. Taken together, this study reveals a comprehensive germline mutation landscape in Chinese prostate cancer patients and discovers 12 novel non-DDR predisposition genes to lay the groundwork for the optimization of genetic screening.

Global burden, risk factors, and temporal trends of ureteral cancer: a comprehensive analysis of cancer registries.

BACKGROUND: Ureteral cancer is a rare cancer. This study aimed to provide an up-to-date and comprehensive analysis on the global trends of ureteral cancer incidence and its association with lifestyle and metabolic risk factors. METHODS: The incidence of ureteral cancer was estimated from the Cancer Incidence in Five Continents Plus and Global Cancer Observatory databases. We analyzed the (1) global incidence of ureteral cancer by region, country, sex, and age group by age-standardized rates (ASR); (2) associated risk factors on a population level by univariable linear regression with logarithm transformation; and (3) incidence trend of ureteral cancer by sex and age group in different countries by Average Annual Percentage Change (AAPC). RESULTS: The global age-standardized rate of ureteral cancer incidence in 2022 was 22.3 per 10,000,000 people. Regions with higher human development index (HDI), such as Europe, Northern America, and East Asia, were found to have a higher incidence of ureteral cancer. Higher HDI and gross domestic product (GDP) and a higher prevalence of smoking, alcohol drinking, physical inactivity, unhealthy dietary, obesity, hypertension, diabetes, and lipid disorder were associated with higher incidence of ureteral cancer. An overall increasing trend of ureteral cancer incidence was observed for the past decade, especially among the female population. CONCLUSIONS: Although ureteral cancer was relatively rare, the number of cases reported was rising over the world. The rising trends among females were more evident compared with the other subgroups, especially in European countries. Further studies could be conducted to examine the reasons behind these epidemiological changes and confirm the relationship with the risk factors identified.

Long-Term Outcomes of Orthotopic Neobladder Versus Ileal Conduit Urinary Diversion in Robot-Assisted Radical Cystectomy (RARC): Multicenter Results from the Asian RARC Consortium.

PURPOSE: Robot-assisted radical cystectomy (RARC) has gained traction in the management of muscle invasive bladder cancer. Urinary diversion for RARC was achieved with orthotopic neobladder and ileal conduit. Evidence on the optimal method of urinary diversion was limited. Long-term outcomes were not reported before. This study was designed to compare the perioperative and oncological outcomes of ileal conduit versus orthotopic neobladder cases of nonmetastatic bladder cancer treated with RARC. PATIENTS AND METHODS: The Asian RARC consortium was a multicenter registry involving nine Asian centers. Consecutive patients receiving RARC were included. Cases were divided into the ileal conduit and neobladder groups. Background characteristics, operative details, perioperative outcomes, recurrence information, and survival outcomes were reviewed and compared. Primary outcomes include disease-free and overall survival. Secondary outcomes were perioperative results. Multivariate regression analyses were performed. RESULTS: From 2007 to 2020, 521 patients who underwent radical cystectomy were analyzed. Overall, 314 (60.3%) had ileal conduit and 207 (39.7%) had neobladder. The use of neobladder was found to be protective in terms of disease-free survival [Hazard ratio (HR) = 0.870, p = 0.037] and overall survival (HR = 0.670, p = 0.044) compared with ileal conduit. The difference became statistically nonsignificant after being adjusted in multivariate cox-regression analysis. Moreover, neobladder reconstruction was not associated with increased blood loss, nor additional risk of major complications. CONCLUSIONS: Orthotopic neobladder urinary diversion is not inferior to ileal conduit in terms of perioperative safety profile and long-term oncological outcomes. Further prospective studies are warranted for further investigation.

Addition of neoadjuvant chemotherapy to a 'quadrifecta' composite in radical cystectomy.

OBJECTIVES: To evaluate the impact of incorporating neoadjuvant chemotherapy (NAC) into the 'quadrifecta' outcomes composite for reporting outcomes of radical cystectomy (RC) creating a pentafecta score. PATIENTS AND METHODS: This is a retrospective multicentre analysis of patients treated with RC, with or without NAC, for bladder cancer between 2002 and 2023. The primary outcome was the effect of adding NAC to a quadrifecta outcomes composite on cancer-specific (CSS) and overall survival (OS). The quadrifecta outcomes composite included a yield of ≥16 lymph nodes, negative soft tissue surgical margin, absence of major complication within 30 days from surgery, and no delay in RC. RESULTS: A total of 590 patients were included in the analyses. A total of 233 (39.5%) patients achieved all quadrifecta outcomes and 82 (13.9%) patients were additionally treated with NAC, achieving the pentafecta. Achieving the quadrifecta outcomes composite was significantly associated with better CSS (hazard ratio [HR] 0.49, 95% confidence interval [CI] 0.32-0.75; P = 0.001) and OS (HR 0.48, 95% CI 0.34-0.69; P < 0.01). The addition of NAC to the quadrifecta composite outcomes significantly improved the discrimination of patients more likely to have better CSS (HR 0.21, 95% CI 0.08-0.57; P = 0.002) and OS (HR 0.26, 95% CI 0.12-0.55; P < 0.01). CONCLUSION: We propose a new pentafecta that may serve as a tool for standardising outcomes reporting and measuring the quality of RC.

Adjuvant intravesical therapy in intermediate-risk non-muscle-invasive bladder cancer.

OBJECTIVE: To evaluate the impact of adjuvant therapy on oncological outcomes in patients with intermediate-risk non-muscle-invasive bladder cancer (NMIBC), as due to the poorly-defined and overlapping diagnostic criteria optimal decision-making remains challenging in these patients. PATIENTS AND METHODS: In this multicentre study, patients treated with transurethral resection of bladder tumour for Ta disease were retrospectively analysed. All patients with low- or high-risk NMIBC were excluded from the analysis. Associations between adjuvant therapy administration with recurrence-free survival (RFS) and progression-free survival (PFS) rates were assessed in Cox regression models. RESULTS: A total of 2206 patients with intermediate-risk NMIBC were included in the analysis. Among them, 1427 patients underwent adjuvant therapy, such as bacille Calmette-Guérin (n = 168), or chemotherapeutic agents, such as mitomycin C or epirubicin (n = 1259), in different regimens up to 1 year. The median (interquartile range) follow-up was 73.3 (38.4-106.9) months. The RFS at 1 and 5 years in patients treated with adjuvant therapy and those without were 72.6% vs 69.5% and 50.8% vs 41.3%, respectively. Adjuvant therapy was associated with better RFS (hazard ratio [HR] 0.79, 95% confidence interval [CI] 0.70-0.89, P < 0.001), but not with PFS (P = 0.09). In the subgroup of patients aged ≤70 years with primary, single Ta Grade 2 <3 cm tumours (n = 328), adjuvant therapy was not associated with RFS (HR 0.71, 95% CI 0.50-1.02, P = 0.06). While in the subgroup of patients with at least one risk factor including patient age >70 years, tumour multiplicity, recurrent tumour and tumour size ≥3 cm (n = 1878), adjuvant intravesical therapy was associated with improved RFS (HR 0.78, 95% CI 0.68-0.88, P < 0.001). CONCLUSION: In our study, patients with intermediate-risk NMIBC benefit from adjuvant intravesical therapy in terms of RFS. However, in patients without risk factors, adjuvant intravesical therapy did not result in a clear reduction in the recurrence rate.

Urinary function in female patients after traditional, organ-sparing and nerve-sparing radical cystectomy for bladder cancer: a systematic review and pooled analysis.

OBJECTIVES: To determine and summarize the available data on urinary, sexual, and health-related quality-of-life (HRQOL) outcomes after traditional radical cystectomy (RC), reproductive organ-preserving RC (ROPRC) and nerve-sparing RC (NSRC) for bladder cancer (BCa) in female patients. METHODS: The PubMed, SCOPUS and Web of Science databases were searched to identify studies reporting functional outcomes in female patients undergoing RC and urinary diversion for the treatment of BCa. The outcomes of interest were voiding function (for orthotopic neobladder [ONB]), sexual function and HRQOL. The following independent variables were derived and included in the meta-analysis: pooled rate of daytime and nighttime continence/incontinence, and intermittent self-catheterization (ISC) rates. Analyses were performed separately for traditional, organ- and/or nerve-sparing surgical approaches. RESULTS: Fifty-three studies comprising 2740 female patients (1201 traditional RC and 1539 organ-/nerve-sparing RC, and 264 nerve-sparing-alone RC) were eligible for qualitative synthesis; 44 studies comprising 2418 female patients were included in the quantitative synthesis. In women with ONB diversion, the pooled rates of daytime continence after traditional RC, ROPRC and NSRC were 75.2%, 79.3% and 71.2%, respectively. The pooled rate of nighttime continence after traditional RC was 59.5%; this rate increased to 70.7% and 71.7% in women who underwent ROPRC and NSRC, respectively. The pooled rate of ISC after traditional RC with ONB diversion in female patients was 27.6% and decreased to 20.6% and 16.8% in patients undergoing ROPRC and NSRC, respectively. The use of different definitions and questionnaires in the assessment of postoperative sexual and HRQOL outcomes did not allow a systematic comparison. CONCLUSIONS: Female organ- and nerve-sparing surgical approaches during RC seem to result in improved voiding function. There is a significant need for well-designed studies exploring sexual and HRQOL outcomes to establish evidence-based management strategies to support a shared decision-making process tailored towards patient expectations and satisfaction. Understanding expected functional, sexual and quality-of-life outcomes is necessary to allow individualized pre- and postoperative counselling and care delivery in female patients planned to undergo RC.

Incidence, risk factors, and temporal trends of penile cancer: a global population-based study.

OBJECTIVES: To examine the global disease burden and country-specific trends of penile cancer incidence by age group and investigate its associations with several factors. MATERIALS AND METHODS: The Global Cancer Observatory database was interrogated for penile cancer incidence. The 10-year cancer incidence rates were collected from the Cancer Incidence in Five Continents Plus. The country-specific data were extracted from the World Health Organization Global Health Observatory and Global Burden of Disease databases for conducting risk factors analysis. The penile cancer incidence was presented using age-standardised rates. Its associations with various factors were examined by linear regression, while the incidence trend was estimated using joinpoint regression and presented as average annual percentage change with 95% confidence intervals in different age groups. RESULTS: There were an estimated 36 068 new cases of penile cancer in 2020. There was a considerable geographical disparity in the disease burden of penile cancer, with South America reporting the highest incidence. Overall, alcohol drinking, human immunodeficiency virus (HIV) infection, and unsafe sex were positively associated with a higher penile cancer incidence, while circumcision was found to be a protective factor. There has been a mixed trend in penile cancer incidence overall, but an increasing trend was found among younger males. CONCLUSIONS: There was a global variation in the penile cancer burden associated with prevalence of alcohol drinking, HIV infection, unsafe sex, and circumcision. The increasing penile cancer incidence in the younger population is worrying and calls for early detection and preventive interventions.

A 2-year prospective evaluation of the Prostate Health Index in guiding biopsy decisions in a large cohort.

OBJECTIVES: To prospectively evaluate how the Prostate Health Index (PHI) impacts on clinical decision in a real-life setting for men with a prostate-specific antigen (PSA) level between 4 and 10 ng/mL and normal digital rectal examination. PATIENTS AND METHODS: Since 2016, the PHI has been available at no cost to eligible men in all Hong Kong public hospitals. All eligible patients who received PHI testing in all public Urology units (n = 16) in Hong Kong between May 2016 and August 2017 were prospectively included and followed up. All included men had a PHI test, with its result and implications explained; the subsequent follow-up plan was then decided via shared decision-making with urologists. Patients were followed up for 2 years, with outcomes including prostate biopsy rates and biopsy findings analysed in relation to the initial PHI measurements. RESULTS: A total of 2828 patients were followed up for 2 years. The majority (82%) had PHI results in the lower risk range (score <35). Knowing the PHI findings, 83% of the patients with elevated PSA decided not to undergo biopsy. In all, 11% and 45% opted for biopsy in the PHI score <35 and ≥35 groups, respectively. The initial detection rate of International Society of Urological Pathology (ISUP) Grade Group (GG) ≥2 cancer was higher in the PHI score ≥35 group (23%) than in the PHI score <35 group (7.9%). Amongst patients with no initial positive biopsy findings, the subsequent positive biopsy rate for ISUP GG ≥2 cancer was higher in the PHI score ≥35 group (34%) than the PHI score <35 group (13%) with a median follow-up of 2.4 years. CONCLUSION: In a real-life setting, with the PHI incorporated into the routine clinical pathway, 83% of the patients with elevated PSA level decided not to undergo prostate biopsy. The PHI pathway also improved the high-grade prostate cancer detection rate when compared to PSA-driven strategies. Higher baseline PHI predicted subsequent biopsy outcome at 2 years. The PHI can serve as a tool to individualise biopsy decisions and frequency of follow-up visits.

Retrograde intrarenal surgery for asymptomatic incidental renal stones: a retrospective, real-world data analysis.

OBJECTIVE: To determine surgical outcomes and stone-free rates (SFRs) when offering upfront retrograde intrarenal surgery (RIRS) to patients with asymptomatic incidental renal stones (AIRS), as active surveillance, shockwave lithotripsy or upfront intervention in patients with AIRS is still a debate among urologists. PATIENTS AND METHODS: This retrospective FLEXible Ureteroscopy Outcomes Registry (FLEXOR), supported by the Team of Worldwide Endourological Researchers (TOWER), examines adult patients who underwent RIRS. We analysed a subset of asymptomatic patients with renal stones on imaging who were treated with RIRS. Data includes patient characteristics, stone specifications, anaesthesia type, perioperative details, complications, and SFR. A multivariable logistic regression analysis was performed to assess factors associated with the SFR. RESULTS: Among 679 patients with AIRS, 640 met the inclusion criteria. The median age was 55 years, with 33.4% being female. In all, 22.1% had positive urine cultures. The median stone diameter was 12 mm, commonly in lower and interpolar locations. RIRS was preferentially performed under general anaesthesia using a reusable scope in 443 cases. Prophylactic antibiotics were administered to 314 patients. The median operation time was 58 min and the median laser time was 24 min. The SFR was 68.8%. The use of holmium laser (odds ratio [OR] 0.21, 95% confidence interval [CI] 0.06-0.63; P < 0.01) and multiple stones (OR 0.38, 95% CI 0.19-0.76; P < 0.01) were factors associated with lower odds of being stone free. Overall complications were minimal, with sepsis in 1.6% of patients. Re-interventions were performed in 76 cases (11.8%), with RIRS being the most common in 67 cases (10.6%). CONCLUSION: Our multicentre real-world study is the first of its kind that highlights the pros and cons of offering RIRS to patients with AIRS and demonstrates a favourable SFR with acceptable complications. Pre-emptively discussing potential re-intervention helps patients make informed decisions, particularly in cases involving large and multiple stones.

Thromboprophylaxis during neoadjuvant chemotherapy for bladder cancer reduces thromboembolism and bleeding.

OBJECTIVES: To assess the risk of venous thromboembolic events (VTEs) and bleeding with or without thromboprophylaxis during neoadjuvant chemotherapy in bladder cancer patients scheduled for radical cystectomy. MATERIALS AND METHODS: We conducted a retrospective cohort study in 4886 patients with non-metastatic bladder cancer undergoing cystectomy across 28 centres in 13 countries between 1990 and 2021. Inverse probability weighting analyses were performed to estimate the effect of thromboprophylaxis on VTE and bleeding. RESULTS: In 147 patients (3%) VTEs were recorded within the first year. These occurred a median (interquartile range [IQR]) of 127 (82-198) days after bladder cancer diagnosis. Bleeding events occurred in 131 patients (3%) within the first year. These occurred a median (IQR) of 101 (83-171) days after cancer diagnosis. In inverse probability weighting analyses, compared to patients without thromboprophylaxis during chemotherapy, patients with thromboprophylaxis had not only a lower risk of VTE (hazard ratio [HR] 0.32, 95% confidence interval [CI] 0.12-0.81; P = 0.016) but also a lower bleeding risk (HR 0.03, 95% CI 0.09-0.12; P <0.0001). The retrospective nature of the study was its main limitation. CONCLUSIONS: In this retrospective analysis, the benefit of thromboprophylaxis during neoadjuvant chemotherapy before cystectomy is in line with data from randomised trials in other malignancies. Our data suggest thromboprophylaxis is protective against VTEs and should be the standard of care during neoadjuvant chemotherapy.

Incidence of complications and urinary incontinence following endoscopic enucleation of the prostate in men with a prostate volume of 80 ml and above: results from a multicenter, real-world experience of 2512 patients.

PURPOSE: To evaluate complications and urinary incontinence (UI) after endoscopic enucleation of the prostate (EEP) stratified by prostate volume (PV). METHODS: We retrospectively reviewed patients with benign prostatic hyperplasia who underwent EEP with different energy sources in 14 centers (January 2019-January 2023). INCLUSION CRITERIA: prostate volume ≥ 80 ml. EXCLUSION CRITERIA: prostate cancer, previous prostate/urethral surgery, pelvic radiotherapy. PRIMARY OUTCOME: complication rate. SECONDARY OUTCOMES: incidence of and factors affecting postoperative UI. Patients were divided into 3 groups. Group 1: PV = 80-100 ml; Group 2 PV = 101-200 ml; Group 3 PV > 200 ml. Multivariable logistic regression analysis was performed to evaluate independent predictors of overall incontinence. RESULTS: There were 486 patients in Group 1, 1830 in Group 2, and 196 in Group 3. The most commonly used energy was high-power Holmium laser followed by Thulium fiber laser in all groups. Enucleation, morcellation, and total surgical time were significantly longer in Group 2. There was no significant difference in overall 30-day complications and readmission rates. Incontinence incidence was similar (12.1% in Group 1 vs. 13.2% in Group 2 vs. 11.7% in Group 3, p = 0.72). The rate of stress and mixed incontinence was higher in Group 1. Multivariable regression analysis showed that age (OR 1.019 95% CI 1.003-1.035) was the only factor significantly associated with higher odds of incontinence. CONCLUSIONS: PV has no influence on complication and UI rates following EEP. Age is risk factor of postoperative UI.

Experts' recommendations in laser use for the treatment of bladder cancer: a comprehensive guide by the European Section of Uro-Technology (ESUT) and Training and Research in Urological Surgery and Technology (TRUST)-Group.

PURPOSE: To identify laser settings and limits applied by experts during laser vaporization (vapBT) and laser en-bloc resection of bladder tumors (ERBT) and to identify preventive measures to reduce complications. METHODS: After a focused literature search to identify relevant questions, we conducted a survey (57 questions) which was sent to laser experts. The expert selection was based on clinical experience and scientific contribution. Participants were asked for used laser types, typical laser settings during specific scenarios, and preventive measures applied during surgery. Settings for a maximum of 2 different lasers for each scenario were possible. Responses and settings were compared among the reported laser types. RESULTS: Twenty-three of 29 (79.3%) invited experts completed the survey. Thulium fiber laser (TFL) is the most common laser (57%), followed by Holmium:Yttrium-Aluminium-Garnet (Ho:YAG) (48%), continuous wave (cw) Thulium:Yttrium-Aluminium-Garnet (Tm:YAG) (26%), and pulsed Tm:YAG (13%). Experts prefer ERBT (91.3%) to vapBT (8.7%); however, relevant limitations such as tumor size, number, and anatomical tumor location exist. Laser settings were generally comparable; however, we could find significant differences between the laser sources for lateral wall ERBT (p = 0.028) and standard ERBT (p = 0.033), with cwTm:YAG and pulsed Tm:YAG being operated in higher power modes when compared to TFL and Ho:YAG. Experts prefer long pulse modes for Ho:YAG and short pulse modes for TFL lasers. CONCLUSION: TFL seems to have replaced Ho:YAG and Tm:YAG. Most laser settings do not differ significantly among laser sources. For experts, continuous flow irrigation is the most commonly applied measure to reduce complications.

Functional and safety outcomes after benign prostatic enlargement surgeries in men with detrusor underactivity compared with normal detrusor contractility: Systematic review and meta-analysis.

INTRODUCTION: Men with detrusor underactivity (DUA) and concomitant bladder outlet obstruction (BOO) due to benign prostatic enlargement (BPE) may present poorer functional outcomes after surgical desobstruction. This study aimed to evaluate the safety and efficacy of BPE surgery in men with DUA compared with those with normal detrusor contractility (NC). MATERIALS AND METHODS: This review was performed according to the 2020 PRISMA framework. A comprehensive literature search was performed until May 7, 2023, using MEDLINE, EMBASE, and Cochrane Database. No date limits were imposed. Only comparative studies were accepted. The primary endpoint was to assess if there was any difference in short- and long-term functional outcomes after BPE surgery in men with DUA and NC. The secondary endpoint was to evaluate the differences in perioperative outcomes and postoperative complications between the two groups. Meta-analysis was performed using Review Manager (RevMan) software. RESULTS: There were 5 prospective nonrandomized studies and 12 retrospective studies, including 1701 DUA and 1993 NC patients. Regarding surgical procedures, there were eight TURP (transurethral resection of the prostate) studies, four GreenLight PVP (photoselective vaporization of the prostate) studies, two HoLEP (Holmium laser enucleation of the prostate) studies, one GreenLight PVP/HoLEP study, one Holmium laser incision of the prostate study, and one study did not report the type of surgery. We did not find a statistically significant difference between the two groups in terms of perioperative outcomes, including postoperative catheterization time, hospitalization time, urinary retention, need to recatheterization, transfusion rate, or urinary tract infections. Also, we found no significant differences in long-term complications, such as bladder neck stenosis or urethral stenosis. Posttreatment bladder recatheterization and retreatment rate for BPE regrowth could not be evaluated properly, because only one study reported these findings. When we analyzed functional outcomes at 3 months, those with NC had lower International Prostatic Symptom Score (IPSS), lower quality-of-life (QoL) score, better maximum flow rate (Qmax), and lower post-voiding residual (PVR) of urine. These results were maintained at 6 months postoperatively, with exception of PVR that showed no difference. However, at 12 and more than 12 months the functional outcomes became similar regarding IPSS and QoL. There were few data about Qmax and PVR at longer follow-up. CONCLUSION: In this meta-analysis, data suggest that BOO surgical treatment in patients with concomitant BPE and DUA appears to be safe. Despite patients with DUA may present worse functional outcomes in the short postoperative term compared with the NC population, IPSS and QoL scores become comparable again after a longer follow-up period after surgery.

Assessment of Prostate and Bladder Cancer Genomic Biomarkers Using Artificial Intelligence: a Systematic Review.

PURPOSE OF REVIEW: The aim of the systematic review is to assess AI's capabilities in the genetics of prostate cancer (PCa) and bladder cancer (BCa) to evaluate target groups for such analysis as well as to assess its prospects in daily practice. RECENT FINDINGS: In total, our analysis included 27 articles: 10 articles have reported on PCa and 17 on BCa, respectively. The AI algorithms added clinical value and demonstrated promising results in several fields, including cancer detection, assessment of cancer development risk, risk stratification in terms of survival and relapse, and prediction of response to a specific therapy. Besides clinical applications, genetic analysis aided by the AI shed light on the basic urologic cancer biology. We believe, our results of the AI application to the analysis of PCa, BCa data sets will help to identify new targets for urological cancer therapy. The integration of AI in genomic research for screening and clinical applications will evolve with time to help personalizing chemotherapy, prediction of survival and relapse, aid treatment strategies such as reducing frequency of diagnostic cystoscopies, and clinical decision support, e.g., by predicting immunotherapy response. These factors will ultimately lead to personalized and precision medicine thereby improving patient outcomes.

Psychological Health of Surgeons in a Time of COVID-19: A Global Survey.

OBJECTIVE: To assess the degree of psychological impact among surgical providers during the COVID-19 pandemic. SUMMARY OF BACKGROUND DATA: The COVID-19 pandemic has extensively impacted global healthcare systems. We hypothesized that the degree of psychological impact would be higher for surgical providers deployed for COVID-19 work, certain surgical specialties, and for those who knew of someone diagnosed with, or who died, of COVID-19. METHODS: We conducted a global web-based survey to investigate the psychological impact of COVID-19. The primary outcomes were the depression anxiety stress scale-21 and Impact of Event Scale-Revised scores. RESULTS: A total of 4283 participants from 101 countries responded. 32.8%, 30.8%, 25.9%, and 24.0% screened positive for depression, anxiety, stress, and PTSD respectively. Respondents who knew someone who died of COVID-19 were more likely to screen positive for depression, anxiety, stress, and PTSD (OR 1.3, 1.6, 1.4, 1.7 respectively, all P < 0.05). Respondents who knew of someone diagnosed with COVID-19 were more likely to screen positive for depression, stress, and PTSD (OR 1.2, 1.2, and 1.3 respectively, all P < 0.05). Surgical specialties that operated in the head and neck region had higher psychological distress among its surgeons. Deployment for COVID- 19-related work was not associated with increased psychological distress. CONCLUSIONS: The COVID-19 pandemic may have a mental health legacy outlasting its course. The long-term impact of this ongoing traumatic event underscores the importance of longitudinal mental health care for healthcare personnel, with particular attention to those who know of someone diagnosed with, or who died of COVID-19.

SARS-CoV-2 infection correlates with male benign prostatic hyperplasia deterioration.

INTRODUCTION: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) affects extra-respiratory systems, with small-scale studies showing worsened male lower urinary tract symptoms (LUTS) after coronavirus disease 2019 (COVID-19). This study explores the correlation between SARS-CoV-2 infection and male benign prostatic hyperplasia (BPH) complications using large-scale real world data. MATERIALS AND METHODS: All male patients attending the public healthcare system in Hong Kong receiving alpha-blocker monotherapy for LUTS from 2021 to 2022 were included in this study. Patients with and without positive polymerase chain reaction (PCR) test for SARS-CoV-2 are selected as the exposure group and control group, respectively. Baseline characteristics are retrieved, with propensity score matching performed to ensure balance of covariates between the two groups. BPH complications were then compared and subgroup analyses were performed. RESULTS: After propensity score matching, 17,986 patients were included for analysis, among which half had PCR-confirmed SARS-CoV-2 infection (n = 8993). When compared to controls, the SARS-CoV-2 group demonstrated statistically significant higher incidence of retention of urine (4.55% vs. 0.86%, p < 0.001), haematuria (1.36% vs. 0.41%, p < 0.001), clinical urinary tract infection (UTI) (4.31% vs. 1.49%, p < 0.001), culture-proven bacteriuria (9.02% vs. 1.97%, p < 0.001) and addition of 5ARI (0.50% vs. 0.02%, p < 0.001). Subgroup analysis demonstrated similar differences across different age groups. There are no statistically significance differences in incidence of retention, haematuria, or addition of 5ARI across different COVID-19 severities. CONCLUSIONS: SARS-CoV-2 infection is associated with increased incidence of urinary retention, haematuria, UTI and the addition of combination therapy in the short term, regardless of COVID-19 severity. This is the largest study demonstrating the detrimental urological effects of SARS-CoV-2 infection.

Comparison Between Holmium:YAG Laser with MOSES Technology vs Thulium Fiber Laser Lithotripsy in Retrograde Intrarenal Surgery for Kidney Stones in Adults: A Propensity Score-matched Analysis From the FLEXible Ureteroscopy Outcomes Registry.

PURPOSE: We evaluated stone-free rate and complications after flexible ureteroscopy for renal stones, comparing thulium fiber laser and holmium:YAG laser with MOSES technology. MATERIALS AND METHODS: Data from adults who underwent flexible ureteroscopy in 20 centers worldwide were retrospectively reviewed (January 2018-August 2021). Patients with ureteral stones, concomitant bilateral procedures, and combined procedures were excluded. One-to-one propensity score matching for age, gender, and stone characteristics was performed. Stone-free rate was defined as absence of fragments >2 mm on imaging within 3 months after surgery. Multivariable logistic regression analysis was performed to evaluate independent predictors of being stone-free. RESULTS: Of 2,075 included patients, holmium:YAG laser with MOSES technology was used in 508 patients and thulium fiber laser in 1,567 patients. After matching, 284 patients from each group with comparable baseline characteristics were included. Pure dusting was applied in 6.0% of cases in holmium:YAG laser with MOSES technology compared with 26% in thulium fiber laser. There was a higher rate of basket extraction in holmium:YAG laser with MOSES technology (89% vs 43%, P < .001). Total operation time and lasing time were similar. Nine patients had sepsis in thulium fiber laser vs none in holmium:YAG laser with MOSES technology (P = .007). Higher stone-free rate was achieved in thulium fiber laser (85% vs 56%, P < .001). At multivariable analysis, the use of thulium fiber laser and ureteral access sheath ≥8F had significantly higher odds of being stone-free. Lasing time, multiple stones, stone diameter, and use of disposable scopes showed significantly lower odds of being stone-free. CONCLUSIONS: This real-world study favors the use of thulium fiber laser over holmium:YAG laser with MOSES technology in flexible ureteroscopy for renal stones by way of its higher single-stage stone-free rate.

Prostate Health Index Density Outperforms Prostate-specific Antigen Density in the Diagnosis of Clinically Significant Prostate Cancer in Equivocal Magnetic Resonance Imaging of the Prostate: A Multicenter Evaluation.

PURPOSE: We compare Prostate Health Index, Prostate Health Index density, and PSA density in predicting clinically significant prostate cancer in MRI-guided prostate biopsy. MATERIALS AND METHODS: This is a multicenter evaluation of prospectively maintained prostate biopsy databases at 10 urology centers. Men with Prostate Health Index and MRI-guided targeted and systematic prostate biopsy performed and without prior prostate cancer diagnosis were included. The additional value of PSA density, Prostate Health Index, and Prostate Health Index density to MRI PI-RADS (Prostate Imaging Reporting & Data System) score was evaluated with multivariable analyses, area under the curve, and decision curve analyses. The proportion of unnecessary biopsies that can be avoided are estimated for clinically significant prostate cancer (International Society of Urological Pathology group ≥2 prostate cancer). RESULTS: A total of 1,215 men were analyzed. Prostate cancer and clinically significant prostate cancer were diagnosed in 51% (617/1,215) and 35% (422/1,215) of men, respectively. Clinically significant prostate cancer was diagnosed in 4.4% (3/68), 15% (72/470), 39% (176/446), and 74% (171/231) of highest PI-RADS score of 2, 3, 4, and 5 lesions, respectively. In multivariable analyses, independent predictors for clinically significant prostate cancer detection included Prostate Health Index (OR 1.04), prostate volume (OR 0.97), and PI-RADS score 4 (OR 2.81) and 5 (OR 8.34). Area under the curve for clinically significant prostate cancer of PI-RADS + Prostate Health Index density (0.85) was superior to PI-RADS + PSA density (0.81), Prostate Health Index density (0.81), Prostate Health Index (0.78), PI-RADS (0.76), PSA density (0.72), and PSA (0.60) in the whole cohort, and the superiority of Prostate Health Index density was also observed in PI-RADS 3 lesions. Decision curve analysis showed Prostate Health Index density achieving the best net clinical benefit in PI-RADS 3 or 4 cases. Among PI-RADS 3 lesions, using cutoffs of PSA density 0.15, Prostate Health Index 38.0, and Prostate Health Index density 0.83 could reduce 58%, 67%, and 72% of unnecessary biopsies, respectively. CONCLUSIONS: Prostate Health Index density outperformed Prostate Health Index or PSA density in clinically significant prostate cancer detection in men with multiparametric MRI performed, and further reduced unnecessary biopsies in PI-RADS 3 lesions.

Oncological and safety profiles in patients undergoing simultaneous transurethral resection (TUR) of bladder tumour and TUR of the prostate.

OBJECTIVES: To determine the oncological impact and adverse events of performing simultaneous transurethral resection of bladder tumour (TURB) and transurethral resection of the prostate (TURP), as evidence on the outcomes of simultaneous TURB for bladder cancer and TURP for obstructive benign prostatic hyperplasia is limited and contradictory. PATIENTS AND METHODS: Patients from 12 European hospitals treated with either TURB alone or simultaneous TURB and TURP (TURB+TURP) were retrospectively analysed. A propensity score matching (PSM) 1:1 was performed with patients from the TURB+TURP group matched to TURB-alone patients. Associations between surgery approach with recurrence-free (RFS) and progression-free (PFS) survivals were assessed in Cox regression models before and after PSM. We performed a subgroup analysis in patients with risk factors for recurrence (multifocality and/or tumour size >3 cm). RESULTS: A total of 762 men were included, among whom, 76% (581) underwent a TURB alone and 24% (181) a TURB+TURP. There was no difference in terms of tumour characteristics between the groups. We observed comparable length of stay as well as complication rates including major complications (Clavien-Dindo Grade ≥III) for the TURB-alone vs TURB+TURP groups, while the latest led to longer operative time (P < 0.001). During a median follow-up of 44 months, there were more recurrences in the TURB-alone (47%) compared to the TURB+TURP group (28%; P < 0.001). Interestingly, there were more recurrences at the bladder neck/prostatic fossa in the TURB-alone group (55% vs 3%, P < 0.001). TURB+TURP procedures were associated with improved RFS (hazard ratio [HR] 0.39, 95% confidence interval [CI] 0.29-0.53; P < 0.001), but not PFS (HR 1.63, 95% CI 0.90-2.98; P = 0.11). Within the PSM cohort of 254 patients, the simultaneous TURB+TURP was still associated with improved RFS (HR 0.33, 95% CI 0.22-0.49; P < 0.001). This was also true in the subgroup of 380 patients with recurrence risk factors (HR 0.41, 95% CI 0.28-0.62; P < 0.001). CONCLUSION: In our contemporary cohort, simultaneous TURB and TURP seems to be an oncologically safe option that may, even, improve RFS by potentially preventing disease recurrence at the bladder neck and in the prostatic fossa.

The current evidence on surgical management for synchronous bilateral renal tumors: results from a scoping review.

PURPOSE: Synchronous bilateral renal masses (SBRM) account for a low percentage of kidney tumors, and there is no current recommendation for their management. The objective was to review evidence regarding the best surgical approach for SBRM in terms of type and timing of surgery. METHODS: A broad literature search was performed on 28th January 2023 using Scopus, PubMed, and EMBASE. Only English papers dealing with adults were included. Meeting abstracts were excluded. RESULTS: Twenty-four papers were accepted and included. SBRM behave less aggressively than metachronous tumors, and partial nephrectomy (PN) is the preferred therapeutic option to preserve renal function. Open, laparoscopic, and robot-assisted approaches were found to be similar in oncological outcomes, though robot-assisted surgery resulted in lower comorbidities. Same-sitting PN was demonstrated to be a safe approach, particularly in the robotic-assisted one. Finally, the same-siting and staged NSS were similar in preserving renal function. CONCLUSIONS: PN should be the desirable treatment for SBRM whenever feasible and if patients are fit, but surgeon expertise should also be taken into the account.