Editor’s Note: The 39th Annual European Association of Urology (EAU) Conference was grandly held from April 5th to 8th, 2024, in Paris, France. As a top-tier event in the global field of urology, the EAU Conference gathered numerous experts and scholars in the urology field to discuss cutting-edge advancements and future trends in urology. At this year’s EAU Conference, Professor Qiang Wei and Professor Lu Yang’s research team from West China Hospital of Sichuan University had multiple studies selected, representing the latest developments in urology in China and contributing significantly to the global advancement of urology. The “Oncology Frontier” magazine has compiled the relevant research below for readers’ enjoyment.
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Prostate Cancer
RARPKB: A Knowledge-Guide Decision Support Platform for Personalized Robot-Assisted Surgery in Prostate Cancer Abstract Number: A0180 First Author: Dr. Jia Kun Li
Background: Robot-assisted radical prostatectomy (RARP) has become a primary surgical intervention for treating prostate cancer. To better address the challenges posed by the complexity of clinical cases, the diversity of prostate cancer, and the limitations of clinical experience, the research team created an online platform called the RARP Knowledge Base (RARPKB), which integrates knowledge from past cases. It aims to provide references for personalized treatment plans for robot-assisted surgery in prostate cancer.
Methods: Over the past twenty years, surgical details, patient information, surgical data, and various statistical results were collected and inputted. Using tools such as MySQL, DataTable, ECharts, and JavaScript, a knowledge-based decision support tool was established, and it was validated and compared using ChatGPT-4 and two evaluation scales.
Results: The platform incorporates 583 studies, 1,589 patient groups, 1,911,968 patients, and 11,986 records, generating a total of 54,834 data entries. This decision support tool can provide personalized surgical plan suggestions and potential complication risks based on patient demographics and surgical information. Compared to ChatGPT-4, RARPKB demonstrated superior performance in authenticity (100% vs. 73%), matching (100% vs. 53%), personalized recommendations (100% vs. 20%), patient matching (100% vs. 0%), and personalized complication recommendations (100% vs. 20%). After use, the system’s usability score averaged 88.88±15.03, and RARPKB achieved a net promoter score of 85.
Conclusion: In summary, RARPKB is the first knowledge base dedicated to robot-assisted surgery in prostate cancer, providing assistance for personalized and complex surgical planning and offering valuable references for the application of artificial intelligence in clinical practice.
Melatonin Inhibits Tumor Growth and Metastasis by Promoting NRF2-Mediated Iron Death Activated via Decrease of Liquid-Liquid Phase Separation Behavior of Androgen Receptor in Prostate Cancer Abstract Number: A0546 First Author: Dr. Xian Yanling Yi
Background: Advanced prostate cancer (PCa) lacks effective treatment methods and is often associated with increased expression of androgen receptors (ARs). Melatonin (MEL) is a multifunctional indoleamine molecule that can inhibit the proliferation of prostate cancer cells, but its specific mechanism is not clear. This study aims to explore the specific molecular mechanism of MEL in PCa to provide a basis for the development of new treatment methods.
Methods: The effects of MEL on prostate cancer proliferation and metastasis were studied through in vitro and in vivo experiments. Co-focal microscopy was used to observe the liquid-liquid phase separation of molecules inside cells. The potential mechanism was preliminarily explored through transcriptome sequencing, and further validation of candidate gene expression levels was conducted using quantitative polymerase chain reaction (qPCR) and Western blotting (WB). In addition, rescue experiments and co-immunoprecipitation (Co-IP) were used to determine the regulatory relationships between genes.
Results: MEL inhibited the proliferation of prostate cancer cells, promoted apoptosis of prostate cancer cells, and reversed the resistance of prostate cancer cells to enzalutamide. Transwell and high-content experiments showed that MEL could also inhibit the metastasis of PCa cells. In vivo experiments showed that intraperitoneal injection of MEL significantly inhibited the growth of subcutaneous transplant tumors and prolonged the survival time of mice. Mechanistically, we found that MEL intervention hindered the liquid-liquid phase separation (LLPS) behavior of ARs, and damaged ARs could form transcriptionally active condensates, leading to a significant decrease in protein levels. The reduced ARs suppressed the expression of GPX4 by reducing the phosphorylation of Nrf2, leading to iron death phenotypes in PCa, namely decreased total glutathione (T-GSH) content and increased reactive oxygen species (ROS) levels. Furthermore, reduced ARs could also decrease the expression of the MCM family (MCM2-10), inhibit the cell cycle, and reduce cell proliferation.
Conclusion: Our research results suggest promising prospects for MEL in the treatment of PCa and may provide new insights for the treatment of advanced PCa.
Is Ipsilateral Systematic Biopsy Combined With Targeted Biopsy the Optimal Substitute for Bilateral Systematic Biopsy Combined With Targeted Biopsy? A Systematic Review and Meta-analysis
Abstract Number: A0058
First Author: Master Qiyou Wu
Background: The detection rate of PCa is high, and currently, it is recommended to perform bilateral systematic biopsy (SB) combined with targeted biopsy (TB) for patients with MRI-visible lesions. However, concerns about its cost, overdiagnosis, overtreatment, and complications have prompted a reassessment of this approach. This study aimed to evaluate the effectiveness of ipsilateral SB (ips-SB) combined with TB (ips-SB+TB) and contralateral SB (con SB) combined with TB (con SB+TB) as potential alternatives to SB+TB.
Methods: Comprehensive literature searches were conducted in the Cochrane, Embase, Ovid, and PubMed databases up to December 2023, and 8 studies were included in the analysis. The relative sensitivities (RRs) and 95% confidence intervals (CIs) of PCa and clinically significant PCa (csPCa) detected by ips-SB, con SB+TB, and SB+TB were calculated. Additionally, the RRs between con SB+TB, con SB+TB, and SB+TB were determined, and subgroup analyses were performed based on the number of unilateral intraglandular lesions in included patients.
Results: The study included 1,874 patients. For the detection rate of csPCa, ips SB+TB showed a detection rate equivalent to SB+TB (RR 0.98, 95% CI: 0.92–1.05, P=0.60). There was a statistically significant difference in csPCa detection between con SB+TB and SB+TB (RR 0.92, 95% CI: 0.86–0.99, P=0.02). Compared to con SB+TB, ips SB+TB diagnosed more PCa and csPCa (PCa: RR 1.04, 95% CI: 0.98–1.09, P=0.18; csPCa: RR 1.07, 95% CI: 1.00–1.14, P=0.07). The detection rates of clinically insignificant prostate cancer (ciPC) were comparable between con-SB+TB and SB+TB (con-SB+TB vs. SB+TB: RR 0.90, 95% CI: 0.79–1.04, P=0.15). However, compared to SB+TB, fewer cases of ciPCa were detected in ips-SB+TB (RR 0.86, 95% CI: 0.75–0.99, P=0.04). Results from subgroup analyses in patients with a single unilateral intraglandular lesion and patients with one or more unilateral intraglandular lesions were similar to the overall analysis.
Conclusion: The conclusion of the review is that ips-SB+TB is more effective than con SB+TB in detecting PCa and csPCa. Additionally, ips SB+TB is equivalent to SB+TB in detecting PCa and csPCa and may potentially replace SB+TB with fewer cores and fewer ciPCa detections.
Insights into the Impact of Neuropsychiatric Disorders on Prostate Diseases: A Two-sample Mendelian Randomization Study
Abstract Number: A0558
First Author: Master Zeyu Han
Background: With the increasing prevalence of prostate diseases in the elderly male population, identifying related risk factors aids in early detection and intervention. Many studies have explored the causal relationship between neuropsychiatric disorders and various diseases affecting important organs. However, there is currently a lack of comprehensive exploration of the causal relationship between neuropsychiatric disorders and prostate diseases. Therefore, this study aimed to elucidate the causal relationship between neuropsychiatric disorders and three prostate diseases, including PCa, benign prostatic hyperplasia (BPH), and prostatitis.
Methods: Univariate, multivariate, and mediation Mendelian randomization (MR) analysis methods were used. Exposure factors included 10 psychiatric disorders and 6 neurological disorders. Summary statistics for exposure and outcome were extracted from genome-wide association studies, and genetic instruments associated with exposure were extracted for subsequent analysis at the genome-wide significance level.
Results: Preliminary analysis suggested that autism spectrum disorders and bipolar affective disorder increased the risk of prostate cancer, while dementia decreased the risk of prostate cancer. Major depressive disorder increased the risk of BPH, and Parkinson’s disease and demyelinating diseases increased the risk of prostatitis. After adjusting for body mass index (BMI), the positive correlation between bipolar affective disorder and prostate cancer and the negative correlation between dementia and prostate cancer persisted. Mediation MR showed a weaker influence of BMI on the causal association. No other diseases were found to have a causal relationship with prostate diseases.
Conclusion: This study provides valuable insights into the risk factors for the occurrence of prostate diseases in patients with neuropsychiatric disorders, aiding in early screening and preventive interventions for patients.
The Impact of Prostate Volume on Prostate Cancer Detection: Comparing mpMRI with TRUS in Biopsy-Naïve Men
Abstract Number: A0658
First Author: Master Jianjun Ye
Background: This study aimed to explore the role of prostate-specific antigen density (PSAD) detected by transrectal ultrasound (TRUS) and multiparametric magnetic resonance imaging (mpMRI) in the diagnosis of prostate cancer (PCa) in men undergoing initial biopsy.
Methods: A retrospective analysis of clinical data from 875 patients who underwent prostate biopsy within 3 months after mpMRI examination between January 2016 and December 2021. The linear relationship between TRUS-prostate volume (TRUS-PV) and mpMRI-prostate volume (mpMRI-PV) was assessed using Pearson correlation coefficients. The diagnostic performance of TRUS-PSAD and mpMRI-PSAD in predicting any PCa and clinically significant PCa (csPCa) was evaluated using ROC curves and compared using the DeLong test.
Results: There was a strong linear correlation and good consistency between TRUS and mpMRI in assessing prostate volume (PV). Significant differences were observed between paired TRUS-PV and mpMRI-PV in each patient. The sensitivity, specificity, positive predictive value, negative predictive value, and area under the curve (AUC) of TRUS-PSAD and mpMRI-PSAD for diagnosing PCa and csPCa were comparable in the overall group.
Conclusion: There was no significant clinical significance in PSAD between significantly different paired PV obtained by different measurement methods. TRUS can be a reliable tool for PV assessment and PSAD dynamic monitoring. TRUS-PSAD can effectively guide PSAD-dominated clinical decisions, optimizing active surveillance diagnostic strategies for suspected PCa and low-risk PCa patients.
Neoadjuvant Disitamab Vedotin Combined with Tislelizumab for Locally Advanced Upper Urinary Tract Carcinoma: A Pilot Study for a Phase II Trial
Abstract Number: A0094 First Author: Professor Yige Bao
Background: Upper urinary tract carcinoma (UTUC) is usually invasive at the initial diagnosis. The pathological complete response (pCR) rate of neoadjuvant chemotherapy for locally advanced UTUC is 10%-20%. This study aimed to investigate the efficacy and safety of the HER2-targeted antibody-drug conjugate (disitamab vedotin) combined with the anti-PD-1 inhibitor (tislelizumab) in neoadjuvant treatment for locally advanced UTUC, regardless of HER2 expression.
Methods: Patients received disitamab vedotin (2.0 mg/kg) combined with tislelizumab (200 mg) every 3 weeks for 4 cycles. The treatment started from March 31, 2022, to April 30, 2023. Patients were followed up monthly in the outpatient clinic until September 30, 2023. The primary endpoints included pCR rate, objective response rate (ORR), and incidence of severe adverse events (SAE). Secondary endpoints included disease control rate (DCR) and progression-free survival (PFS).
Results: Three patients (21.43%) achieved pCR. Eight patients (57.14%) achieved partial pathological remission. Three patients (21.43%) achieved disease stabilization. The overall ORR was 78.57% (11/14), with an ORR of 90.00% (9/10) in HER2-positive patients and 50.00% (2/4) in HER2-negative patients. One HER2-negative patient experienced myocarditis. The incidence of SAE was 7.14% (1/14). The DCR was 100% (14/14). All patients survived until the end of the study, and the median PFS was not reached.
Conclusion: In locally advanced UTUC, regardless of HER2 expression, disitamab vedotin combined with tislelizumab showed promising efficacy with a pCR rate of 21.43% and an ORR of 78.57%. The combination therapy also demonstrated manageable safety. This study is a prospective, single-arm phase II trial (WUTSUP-02) of neoadjuvant treatment for locally advanced UTUC (cT2-4N0-2M0). The ongoing WUTSUP-02 trial will further evaluate the efficacy and safety of disitamab vedotin combined with tislelizumab in UTUC patients.
Biological Age Acceleration was Positively Associated with Overactive Bladder
Abstract Number: A0786
First Author: Master Weichao Huang
Background: This study, based on a population-based cross-sectional study, aimed to explore the association between biological age acceleration and overactive bladder (OAB).
Methods: In this study, the authors calculated three biological age parameters based on 10 clinically accessible age-related indicators. These parameters included Klmera-Doubal method (KDM) biological age, phenotypic age, and homeostatic dysregulation (HD) calculated based on Mahalanobis distance. The difference between KDM biological age and chronological age, as well as phenotypic age and chronological age, was defined as KDM biological age acceleration and phenotypic age acceleration, respectively.
Results: In weighted logistic regression analysis, phenotypic age acceleration and HD were positively associated with the risk of OAB occurrence. For phenotypic age acceleration, each year of phenotypic age acceleration was associated with a 2.8% increase in the risk of OAB. Each unit increase in log HD was associated with a 12.6% increase in the risk of OAB. However, no statistically significant correlation was observed between KDM biological age acceleration and OAB in the logistic regression model.
Conclusion: In restricted cubic spline, there was a significant nonlinear relationship between KDM biological age acceleration and OAB, while the nonlinear relationship between phenotypic age acceleration and HD was not significant. The positive correlation between biological age acceleration and OAB was stable in most subgroups.
Director of the Department of Urology, West China Center of Medical Sciences, Sichuan University
Deputy Director of the Urology Branch of the Chinese Medical Association
Vice President of the Urology Physicians Branch of the Chinese Medical Doctor Association
Deputy Director of the Prostate Cancer and Kidney Cancer Branch of the China Anti-Cancer Association
Deputy Director of the Prostate Cancer and Kidney Cancer Branch of the Chinese Society of Clinical Oncology (CSCO)
Director of the Clinical Research Center for Kidney Disease and Urological Diseases in Sichuan Province
Chairman of the Robotic Surgery Physicians Branch of the Sichuan Medical Association
Chairman of the Prostate Cancer and Male Reproductive Tumors Branch of the Sichuan Anti-Cancer Association
Chairman of the Urology Branch of the Chengdu Medical Association
Associate Director of the Department of Urology, West China Hospital, Sichuan University
Associate Professor, Doctoral Supervisor
Member and Secretary-General of the Urology Branch of the Chinese Medical Association
Member of the Basic Research Group of the Urology Branch of the Chinese Medical Association
Youth Member of the Urology Branch of the Chinese Society of Integrated Traditional Chinese and Western Medicine
Youth Member of the Urology Health Promotion Branch of the Chinese Medical Promotion Association
Member of the Tumor Group of the Urology Branch of the Chinese Society of Integrated Traditional Chinese and Western Medicine
Academic and Technical Leader Reserve Candidate of the Sichuan Provincial Health Commission
Deputy Chairman of the Urology Physicians Branch of the Sichuan Medical Association
Deputy Chairman of the Urology Branch of the Sichuan Health Promotion Association
Expert and Secretary of the Urology Medical Quality Control Center of the Sichuan Provincial Health Commission
Deputy Editor-in-Chief of Genitourinary Oncology, Frontiers in OncologyTop of Form
