A systematic review of robot-assisted simple prostatectomy outcomes by prostate volume.

PURPOSE: The aim of our study is to assess the differences in functional outcomes during the perioperative and postoperative period after RASP depending on BPH volume. METHODS: We searched 2 databases: MEDLINE (PubMed) and Google Scholar using the following search query: robot* AND "simple prostatectomy". The search strategy and review protocol are available at Prospero (CRD42024508071). RESULTS: We included 25 articles published between 2008 and 2023. Preoperatively, patients with prostate size < 100 cm3 had more severe symptoms while postoperatively all of them had only mild lower urinary tract symptoms (LUTS). In larger BPH, two authors reported moderate LUTS after RASP: Fuschi [1] (mean IPSS 8.09 ± 2.41) and Stolzenburg [2] (mean IPSS 8 ± 2.7). Postoperative Qmax was also noticeably higher in smaller BPH (mean value range 28.5-55.5 ml/s) compared to larger BPH (mean Qmax 18-29.6 ml/s), although in both groups it was within the normal range. Postoperative post-void residual (PVR) was normal as well except in one study by Stolzenburg et al. [2]. Blood loss was comparable between the groups. The complications rate in general was low. CONCLUSION: RASP is effective in terms of subjective and objective urination indicators, and a safe procedure for BPH. In the lack of data on implementation of RASP in small prostate volumes, this procedure can be seen as an upper size «limitless¼ treatment alternative. Currently, comparative data regarding prostate volume is lacking, and future trials with subgroups analysis related to BPH volume might help to address this issue.

Perioperative platform for muscle-invasive bladder cancer trials: designs and endpoints.

PURPOSE OF REVIEW: This review explores the design and endpoints of perioperative platforms in clinical trials for muscle-invasive bladder cancer (MIBC). RECENT FINDINGS: The choice of clinical trial design in perioperative platforms for MIBC must align with specific research objectives to ensure robust and meaningful outcomes. Novel designs in perioperative platforms for MIBC integrate bladder-sparing approaches. Primary endpoints such as pathological complete response and disease-free survival are highlighted for their role in expediting trial results in perioperative setting. Incorporating patient-reported outcomes is important to inform healthcare decision makers about the outcomes most meaningful to patients. Given the growing body of evidence, potential biomarkers, predictive and prognostic tools should be considered and implemented when designing trials in perioperative platforms for MIBC. SUMMARY: Effective perioperative platforms for MIBC trials are critical in enhancing patient outcomes. The careful selection and standardization of study designs and endpoints in the perioperative platform are essential for the successful implementation of new therapies and the advancement of personalized treatment approaches in MIBC.

The potential benefits of concomitant statins treatment in patients with non-muscle-invasive bladder cancer.

OBJECTIVE: To investigate the influence of statins on the survival outcomes of patients with non-muscle-invasive bladder cancer (NMIBC) treated with adjuvant intravesical bacille Calmette-Guérin (BCG) immunotherapy. PATIENTS AND METHODS: A retrospective cohort of consecutive patients with NMIBC who received intravesical BCG therapy from 2001 to 2020 and statins prescription were identified. Overall survival (OS), cancer-specific survival (CSS), recurrence-free survival (RFS), and progression-free survival (PFS) were analysed between the Statins Group vs No-Statins Group using Kaplan-Meier method and multivariable Cox regression. RESULTS: A total of 2602 patients with NMIBC who received intravesical BCG were identified. The median follow-up was 11.0 years. On Kaplan-Meier analysis, the Statins Group had significant better OS (P < 0.001), CSS (P < 0.001), and PFS (P < 0.001). Subgroup analysis indicated statins treatment started before BCG treatment had better CSS (P = 0.02) and PFS (P < 0.01). Upon multivariable Cox regression analysis, the 'statins before BCG' group was an independent protective factor for OS (hazard ratio [HR] 0.607, 95% confidence interval [CI] 0.514-0.716), and CSS (HR 0.571, 95% CI 0.376-0.868), but not RFS (HR 0.885, 95% CI 0.736-1.065), and PFS (HR 0.689, 95% CI 0.469-1.013). CONCLUSIONS: Statins treatment appears to offer protective effects on OS and CSS for patients with NMIBC receiving adjuvant intravesical BCG.

Young age and adequate BCG are key factors for optimal BCG treatment efficacy in non-muscle-invasive bladder cancer.

OBJECTIVE: To investigate the impact of ageing on survival outcomes in Bacillus Calmette-Guérin (BCG) treated non-muscle invasive bladder cancer (NMIBC) patients and its synergy with adequate BCG treatment. METHOD: Patients with NMIBC who received BCG treatment from 2001 to 2020 were divided into group 1 (< = 70 years) and group 2 (> 70 years). Overall Survival (OS), Cancer-Specific Survival (CSS), Recurrence-Free Survival (RFS), and Progression-Free Survival (PFS) were analyzed using the Kaplan-Meier method. Multivariable Cox regression analysis was used to adjust potential confounding factors and to estimate Hazard Ratio (HR) and 95% Confidence Interval (CI). Subgroup analysis was performed according to adequate versus inadequate BCG treatment. RESULTS: Overall, 2602 NMIBC patients were included: 1051 (40.4%) and 1551 (59.6%) in groups 1 and 2, respectively. At median follow-up of 11.0 years, group 1 (< = 70 years) was associated with better OS, CSS, and RFS, but not PFS as compared to group 2 (> 70 years). At subgroup analysis, patients in group 1 treated with adequate BCG showed better OS, CSS, RFS, and PFS as compared with inadequate BCG treatment in group 2, while patients in group 2 receiving adequate BCG treatment had 41% less progression than those treated with inadequate BCG from the same group. CONCLUSIONS: Being younger (< = 70 years) was associated with better OS, CSS, and RFS, but not PFS. Older patients (> 70 years) who received adequate BCG treatment had similar PFS as those younger with adequate BCG treatment.

Risk factors of hematoma after SWL for renal calculi: analysis from RCTs and a literature review.

OBJECTIVE: To identify risk factors of perinephric hematoma following extracorporeal shockwave lithotripsy (SWL) for renal calculi through combined analysis of two randomized controlled trials. PATIENTS AND METHODS: This post-hoc analysis included adult patients with solitary renal calculi ranging from 5 to 15 mm, treated with SWL between 2016 and 2022. All patients received cross-sectional imaging (either non-contrast computer tomography scan or magnetic resonance imaging) two days post-SWL to assess the presence and severity of perinephric hematoma. RESULTS: Among 573 patients analyzed, 173 (30.9%) developed perinephric hematoma by Day 2 post-SWL. Multivariate logistic regression identified higher total energy delivered (odds ratio [OR] = 1.533, p = 0.003), higher mean stone density (OR = 2.603, p = 0.01), higher maximal stone density (OR = 3.578, p = 0.03), and lower pole stone location (OR = 1.545, p = 0.029) were risk factors for the development of hematoma. Conversely, the stepwise ramping protocol was a protective factor for hematoma formation. (OR = 0.572, p = 0.042). CONCLUSIONS: This study elucidates key factors influencing the risk of perinephric hematoma post-SWL, highlighting the importance of procedural adjustments such as the stepwise ramping protocol to reduce complications. These insights call for targeted patient and treatment strategy optimization to enhance SWL safety and efficacy.

High Levels of Incidental COVID-19 Infection in Emergency Urology Admissions: A Propensity Score-Matched Real World Data Analysis across Surgical Specialties.

Background: An incidental COVID-19 infection is often found in patients admitted for non-COVID-19-related conditions. This study aims to investigate the incidence of COVID-19 infections across surgical specialties including urology, general surgery, and orthopaedic surgery. Methods: This is a retrospective cohort study based on a territory-wide electronic database in Hong Kong. All emergency in-hospital admissions under the urology, general surgery, and orthopaedic surgery divisions in the public healthcare system in Hong Kong from January to September 2022 were included. All patients were routinely screened for SARS-CoV-2, based on admission protocols during the investigation period. Baseline characteristics were retrieved, with 1:1:1 propensity score matching being performed. Incidental COVID-19 rates were then compared across specialties. Results: A total of 126,034 patients were included. After propensity score matching, the baseline characteristics were well balanced, and 8535 patients in each group were analysed. Urology admission was noted to have a statistically significant higher incidence of incidental COVID-19 at 9.3%, compared to general surgery (5.4%) or orthopaedic surgery (5.6%). Amongst urology patients with incidental COVID-19 infection, 35.8% were admitted for retention of urine, 27.9% for haematuria, and 8.6% for a urinary tract infection. Conclusions: This large-scale cohort study demonstrated that incidental COVID-19 rates differ between surgical specialties, with urology having the highest proportion of incidental COVID-19 infection.

Bladder sparing options for muscle-invasive bladder cancer.

PURPOSE OF REVIEW: This review critically evaluates the current state of bladder-sparing options in muscle-invasive bladder cancer (MIBC) and provides an overview of future directions in the field. RECENT FINDINGS: Bladder-sparing treatments have emerged as viable alternatives to radical cystectomy (RC) for selected patients with MIBC, especially in those who are unfit for RC or elect bladder preservation. Numerous studies have assessed the efficacy of trimodal therapy (TMT), with outcomes comparable to RC in a subgroup of well selected patients. Combining immunotherapy with conventional treatments in bladder-sparing approaches can yield promising outcomes. Current research is making significant progress in optimizing treatment protocols by exploring new combinations of systemic therapy agents, innovative drug delivery methods, and biomarker-based approaches. Furthermore, clinical markers of response are being tested to ensure adequate response assessment. SUMMARY: Bladder preservation promise to offer a viable alternative to RC for selected patients with MIBC with the potential to improve patient quality of life. Careful patient selection and ongoing research are essential to optimize patient selection, response assessment, and salvage strategies. As evidence continues to evolve, the role of bladder preservation in MIBC is likely to expand, providing patients with more treatment options tailored to their needs and preferences.

The Association of Obstructive Sleep Apnea with Urological Cancer Incidence and Mortality-A Systematic Review and Meta-analysis.

BACKGROUND AND OBJECTIVE: While obstructive sleep apnea (OSA) and urological cancer are both strongly associated with hypoxia, controversy exists regarding their association with each other. This study aims to summarize and synthesize evidence to clarify the association between OSA and urological cancer incidence and mortality. METHODS: According to a prespecified protocol, PubMed, Embase, Cochrane Library, and Scopus were searched from inception to November 16, 2023, for observational and randomized studies reporting the association of OSA with urological cancer incidence or mortality. We pooled maximally covariate-adjusted hazard ratios (HRs) using a random-effects inverse variance-weighted model. Two reviewers independently assessed the quality of evidence using the Newcastle-Ottawa Scale and the Grading of Recommendations, Assessment, Development and Evaluation framework. KEY FINDINGS AND LIMITATIONS: From 1814 records, we included 12 studies comprising 9 290 818 participants in total, of which nine studies were analyzed quantitatively. OSA patients had an increased risk of kidney (HR: 1.75, 95% confidence interval [CI]: 1.21-2.53) and bladder (HR: 1.76, 95% CI: 1.05-2.96) cancer. However, OSA was not associated with prostate cancer incidence (HR: 1.29, 95% CI: 0.82-2.04). We systematically reviewed evidence surrounding OSA and testicular cancer incidence and urological cancer mortality. CONCLUSIONS AND CLINICAL IMPLICATIONS: OSA may be associated with a higher risk of kidney and bladder cancer, but not prostate cancer. Future work may help clarify the possibility of a dose-response relationship between OSA and urological cancer, and the effect of OSA treatment on urological cancer incidence or progression. PATIENT SUMMARY: This research highlights a potential longitudinal association between OSA and kidney and bladder cancer, but not prostate cancer.

Impact of Pre-Operative Ureteroscopy on Bladder Recurrence Following Nephroureterectomy for UTUC.

(1) Introduction: Diagnostic ureteroscopy (URS) is an important component in the workup of upper tract urothelial carcinoma (UTUC). Whether URS was associated with increased recurrence in the bladder was not fully concluded. The current study aimed to evaluate the implication of URS on the incidences of intravesical recurrence following radical nephroureterectomy (RNU) in non-metastatic UTUC patients without prior history of bladder cancer via multi-institutional data. (2) Patients and Methods: Data were obtained from the Clinical Research Office of the Endourology Society Urothelial Carcinomas of the Upper Tract (CROES-UTUC) registry, a prospective, multicentre database. Patients with non-metastatic UTUC treated with RNU were divided into two groups: those undergoing upfront RNU and those having diagnostic URS prior to RNU. Intravesical recurrence-free survival (IVRS) was the primary endpoint, evaluated through Kaplan-Meier analysis and multivariate Cox regression. Cases with adequate follow-up data were included. (3) Results: The analysis included 269 patients. Of these, 137 (50.9%) received upfront RNU and 132 (49.1%) received pre-RNU URS. The URS group exhibited an inferior 24-month IVRS compared to the upfront RNU group (HR = 1.705, 95% CI = 1.082-2.688; p = 0.020). Multivariate analysis confirmed URS as the only significant predictor of IVR (p = 0.019). Ureteric access sheath usage, flexible ureteroscopy, ureteric biopsy, retrograde contrast studies, and the duration of URS did not significantly affect IVRS. (4) Conclusions: Diagnostic URS prior to RNU was found to be associated with an increased risk of IVR in patients with UTUC. The risk was not significantly influenced by auxiliary procedures during URS. Physicians were advised to meticulously evaluate the necessity of diagnostic URS.

Robot-assisted Single-port Radical Prostatectomy with the SHURUI SP and da Vinci SP Platforms: Comparison of the Technology, Intraoperative Performance, and Outcomes.

Background and objective: The purpose-built SHURUI single-port (SP) robotic platform has recently been introduced for several procedures in urology, general surgery, and gynecology. However, comparative evidence on its performance in relation to earlier models such as the da Vinci SP is lacking. Our aim was to compare the step-by-step techniques and 1-yr outcomes for radical prostatectomy (RP) between the SHURUI SP and da Vinci SP robots. Methods: Data were retrieved from two prospectively maintained databases. The SHURUI SP robot was used to perform RP in 34 patients in China (September 2021 to August 2022); the da Vinci SP robot was used to perform 100 consecutive RP cases in the USA (June 2019 to October 2020). A comparative analysis was conducted before and after 1:1 propensity score matching for age, body mass index, American Urological Association symptom score, prostate size, prostate-specific antigen (PSA) levels, biopsy grade group, and D'Amico risk group. Intraoperative performance and short-term oncological and continence outcomes were compared between the groups. Biochemical recurrence was defined as two consecutive postoperative PSA levels >0.2 ng/ml. Continence was defined as full recovery of urinary control without the use of pads. The Kaplan-Meier method was used to estimate continence recovery curves, and a log-rank test for trend was used to detect ordered differences in continence recovery between the SHURUI SP and da Vinci SP groups after surgery. Key findings and limitations: For the matched SHURUI and da Vinci groups, median age (69 vs 69 yr), median PSA (8.4 vs 7.1 ng/ml), and the proportion of patients with low-risk (33.3% vs 29.6%), intermediate-risk (66.7% vs 63%), and high-risk disease (0% vs 7.4%) were comparable (all p > 0.05). All surgeries were successfully accomplished without conversion. A higher percentage of cases in the SHURUI group involved extraperitoneal access (81.5% vs 0%; p < 0.001) and a pure SP approach (25.9% vs 0%; p = 0.01), while a higher percentage of cases in the da Vinci group had nerve-sparing surgery. The median total operative (215 vs 110 min; p < 0.001) and median console time (162 vs 75 min; p < 0.001) were significantly longer in the SHURUI group. No intraoperative or major postoperative complications were observed in either group. Rates of positive surgical margins (18.5% vs 14.8%; p = 1.0) and extraprostatic extension (14.8% vs 29.6%; p = 0.19) were similar. At median follow-up of 13.5 versus 15.9 mo, none of the patients had experienced biochemical recurrence. At 1 yr after surgery, the continence rate was 96.3% in both groups. Conclusions: Despite differences in driving mechanisms between the two SP robotic systems, RP can be performed safely and effectively with the SHURUI RP robot during the initial learning phase, with similar short-term oncological and continence outcomes to those with the da Vinci SP robot. Patient summary: We compared two surgical robots (SHURUI SP and da Vinci SP) used to perform robotic surgery to remove the prostate through a single keyhole incision instead of multiple incisions. Our results show comparable technology and similar surgical and short-term cancer control outcomes for the two robots.

Monopolar versus bipolar transurethral resection of bladder Tumour: post-hoc analysis of a prospective trial.

INTRODUCTION: Previously, in a randomised trial we demonstrated bipolar transurethral resection of bladder tumor (TURBT) could achieve a higher detrusor sampling rate than monopolar TURBT. We hereby report the long-term oncological outcomes following study intervention. METHODS: This is a post-hoc analysis of a randomized phase III trial comparing monopolar and bipolar TURBT. Only patients with pathology of non-muscle invasive bladder cancer (NMIBC) were included in the analysis. Per-patient analysis was performed. Primary outcome was recurrence-free survival (RFS). Secondary outcomes included progression-free survival (PFS), cancer-specific survival (CSS) and overall survival (OS). RESULTS: From the initial trial, 160 cases were randomised to receive monopolar or bipolar TURBT. 24 cases of non-urothelial carcinoma, 22 cases of muscle-invasive bladder cancer, and 9 cases of recurrences were excluded. A total of 97 patients were included in the analysis, with 46 in the monopolar and 51 in the bipolar group. The median follow-up was 97.1 months. Loss-to-follow-up rate was 7.2%. Regarding the primary outcome of RFS, there was no significant difference (HR = 0.731; 95%CI = 0.433-1.236; P = 0.242) between the two groups. PFS (HR = 1.014; 95%CI = 0.511-2.012; P = 0.969), CSS (HR = 0.718; 95%CI = 0.219-2.352; P = 0.584) and OS (HR = 1.135; 95%CI = 0.564-2.283; P = 0.722) were also similar between the two groups. Multifocal tumours were the only factor that was associated with worse RFS. CONCLUSION: Despite the superiority in detrusor sampling rate, bipolar TURBT was unable to confer long-term oncological benefits over monopolar TURBT.

Pre-Op Hydronephrosis Predicts Outcomes in Patients Receiving Robot-Assisted Radical Cystectomy.

INTRODUCTION: Robot-assisted radical cystectomy (RARC) has gained momentum in the management of muscle invasive bladder cancer (MIBC). Predictors of RARC outcomes are not thoroughly studied. We aim to investigate the implications of preoperative hydronephrosis on oncological outcomes. PATIENTS AND METHODS: This study analysed data from the Asian RARC consortium, a multicentre registry involving nine Asian centres. Cases were divided into two groups according to the presence or absence of pre-operative hydronephrosis. Background characteristics, operative details, perioperative outcomes, and oncological results were reviewed. Outcomes were (1) survival outcomes, including 10-year disease-free survival (DFS) and overall survival (OS), and (2) perioperative and pathological results. Multivariate regression analyses were performed on survival outcomes. RESULTS: From 2007 to 2020, 536 non-metastatic MIBC patients receiving RARC were analysed. 429 had no hydronephrosis (80.0%), and 107 (20.0%) had hydronephrosis. Hydronephrosis was found to be predictive of inferior DFS (HR = 1.701, p = 0.003, 95% CI = 1.196-2.418) and OS (HR = 1.834, p = 0.008, 95% CI = 1.173-2.866). Subgroup analysis demonstrated differences in the T2-or-above subgroup (HR = 1.65; p = 0.004 in DFS and HR = 1.888; p = 0.008 in OS) and the T3-or-above subgroup (HR = 1.757; p = 0.017 in DFS and HR = 1.807; p = 0.034 in OS). CONCLUSIONS: The presence of preoperative hydronephrosis among MIBC patients carries additional prognostic implications on top of tumour staging. Its importance in case selection needs to be highlighted.

Artificial intelligence for predicting response to neoadjuvant chemotherapy for bladder cancer A comprehensive systematic review and meta-analysis.

INTRODUCTION: Neoadjuvant cisplatin-based combination chemotherapy (NAC) followed by radical cystectomy is the standard of care for cisplatin-fit patients harboring muscle-invasive bladder cancer (MIBC). Prediction of response to NAC is essential for clinical decision-making regarding alternatives in case of non-response, and bladder-sparing in case of complete response. This research aimed to assess the performance of machine learning in predicting therapeutic response following NAC treatment in patients with MIBC. METHODS: A systematic review adhering to the PRISMA guidelines was conducted until July 2023. The study integrated articles relating to artificial intelligence and NAC response in MIBC from various databases. The quality of articles was evaluated using the Quality Assessment Tool for Diagnostic Accuracy Studies 2 (QUADAS-2). A meta-analysis was subsequently performed on selected studies to determine the sensitivity and specificity of machine learning algorithms in predicting NAC response. RESULTS: Of 655 articles identified, 12 studies comprising 1523 patients were included, and four studies were eligible for meta-analysis. The sensitivity and specificity of the studies were 0.62 (95% confidence interval [CI] 0.50-0.72) and 0.82 (95% CI 0.72-0.89), respectively, with a heterogeneity score (I2) of 38.5%. The machine learning algorithms used computed tomography, genetic, and anatomopathologic data as input and exhibited promising potential for predicting NAC response. CONCLUSIONS: Machine-learning algorithms, especially those using computed tomography, genetic, and pathologic data, demonstrate significant potential for predicting NAC response in MIBC. Standardization of methodologic data analysis and response criteria are needed as validation studies.

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.

Cardio-oncology in advanced prostate cancer.

Treatment intensification with androgen deprivation therapy (ADT) and androgen receptor pathway inhibitors (ARPi) have led to improved survival in advanced prostate cancer. However, ADT is linked to significant cardiovascular toxicity, and ARPi also negatively impacts cardiovascular health. Together with a higher prevalence of baseline cardiovascular risk factors reported among prostate cancer survivors at diagnosis, there is a pressing need to prioritise and optimise cardiovascular health in this population. Firstly, While no dedicated cardiovascular toxicity risk calculators are available, other tools such as SCORE2 can be used for baseline cardiovascular risk assessment. Next, selected patients on combination therapy may benefit from de-escalation of ADT to minimise its toxicities while maintaining cancer control. These patients can be characterised by an exceptional PSA response to hormonal treatment, favourable disease characteristics and competing comorbidities that warrant a less aggressive treatment regime. In addition, emerging molecular and genomic biomarkers hold the potential to identify patients who are suited for a de-escalated treatment approach either with ADT or with ARPi. One such biomarker is AR-V7 splice variant that predicts resistance to ARPi. Lastly, optimization of modifiable cardiovascular risk factors for patients through a coherent framework (ABCDE) and exercise therapy is equally important. This article aims to comprehensively review the cardiovascular impact of hormonal manipulation in metastatic hormone-sensitive prostate cancer, propose overarching strategies to mitigate cardiovascular toxicity associated with hormonal treatment, and, most importantly, raise awareness about the detrimental cardiovascular effects inherent in our current management strategies involving hormonal agents.

PiRNA-4447944 promotes castration-resistant growth and metastasis of prostate cancer by inhibiting NEFH expression through forming the piRNA-4447944-PIWIL2-NEFH complex.

Castration-resistant prostate cancer (CRPC) is the leading cause of prostate cancer (PCa)-related death in males, which occurs after the failure of androgen deprivation therapy (ADT). PIWI-interacting RNAs (piRNAs) are crucial regulators in many human cancers, but their expression patterns and roles in CRPC remain unknown. In this study, we performed small RNA sequencing to explore CRPC-associated piRNAs using 10 benign prostate tissues, and 9 paired hormone-sensitive PCa (HSPCa) and CRPC tissues from the same patients. PiRNA-4447944 (piR-4447944) was discovered to be highly expressed in CRPC group compared with HSPCa and benign groups. Functional analyses revealed that piR-4447944 overexpression endowed PCa cells with castration resistance ability in vitro and in vivo, whereas knockdown of piR-4447944 using anti-sense RNA suppressed the proliferation, migration and invasion of CRPC cells. Additionally, enforced piR-4447944 expression promoted in vitro migration and invasion of PCa cells, and reduced cell apoptosis. Mechanistically, piR-4447944 bound to PIWIL2 to form a piR-4447944/PIWIL2 complex and inhibited tumor suppressor NEFH through direct interaction at the post-transcriptional level. Collectively, our study indicates that piR-4447944 is essential for prostate tumor-propagating cells and mediates androgen-independent growth of PCa, which extends current understanding of piRNAs in cancer biology and provides a potential approach for CRPC treatment.

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.

Outcomes and considerations for retrograde intrarenal surgery (RIRS) in the setting of multiple and large renal stones (>15 mm) in children: Findings from multicentre and real-world setting.

Purpose: The aim of this study is to evaluate the outcomes of retrograde intra renal surgery (RIRS) in the setting of large or multiple stones in children (<18 years). Materials and Methods: Retrospective analysis was performed of paediatric RIRS cases at nine centres worldwide over a 6-year period. Patients were divided into two groups: Group 1 had a single stone <15 mm. Group 2 had either multiple stones, maximum stone diameter of >15 mm, or both. Outcomes included stone free rate (SFR) and complications within 30 days. Results: In total, 344 patients were included with 197 and 147 in Groups 1 and 2, respectively. Ureteric access sheaths were more frequently used in Group 2 (39.5% vs. 56.8%, p = 0.021). The operation time was significantly longer in Group 2 (p < 0.001). SFR after a single procedure was 84.7% in Group 1 and 63.7% in Group 2. Overall complication rates in Groups 1 and 2 were 7.6% and 33.3%, respectively. The most frequently reported complication in both groups was post-operative fever (4.4% vs. 14%, p = 0.004). The rate of Clavien I/II complications in groups 1 and 2 was 6% and 25.1%, respectively (p < 0.05). The rate of Clavien ≥ III complications in groups 1 and 2 was 1.6% and 8.1%, respectively (p < 0.05). On multivariate analysis, total operation time, stone size and multiplicity were significant predictors of residual fragments. Conclusions: RIRS can be performed in paediatric cases with large and multiple stone burdens, but the complication rate is significantly higher when compared to smaller stones.

The establishment of kidney cancer organoid line in drug testing.

INTRODUCTION: Kidney cancer is a common urological malignancy worldwide with an increasing incidence in recent years. Among all subtypes, renal cell carcinoma (RCC) represents the most predominant malignancy in kidney. Clinicians faced a major challenge to select the most effective and suitable treatment regime for patients from a wide range of modalities, despite improved understanding and diagnosis of RCC. OBJECTIVE: Recently, organoid culture gained more interest as the 3D model is shown to be highly patient specific which is hypothetically beneficial to the investigation of precision medicine. Nonetheless, the development and application of organotypic culture in RCC is still immature, therefore, the primary objective of this study was to establish an organoid model for RCC. MATERIALS AND METHODS: Patients diagnosed with renal tumor and underwent surgical intervention were recruited. RCC specimen was collected and derived into organoids. Derived organoids were validated by histological examminations, sequencing and xenograft. Drug response of organoids were compared with resistance cell line and patients' clinical outcomes. RESULTS: Our results demonstrated that organoids could be successfully derived from renal tumor and they exhibited high concordance in terms of immunoexpressional patterns. Sequencing results also depicted concordant mutations of driver genes in both organoids and parental tumor tissues. Critical and novel growth factors were discovered during the establishment of organoid model. Besides, organoids derived from renal tumor exhibited tumorigenic properties in vivo. In addition, organoids recapitulated patient's in vivo drug resistance and served as a platform to predict responsiveness of other therapeutic agents. CONCLUSION: Our RCC organoid model recaptiluated histological and genetic features observed in primary tumors. It also served as a potential platform in drug screening for RCC patients, though future studies are necessary before translating the outcomes into clinical practices.