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Tai-Lung ChaTaiwan
Moderator
Novel Target for GU Cancer Metastasis and TherapeuticsCancer progression is shaped by both cell-intrinsic adaptations and complex extrinsic interactions within the tumor microenvironment (TME). Here, we identify a transmembrane protein, Meta1, as a shared therapeutic target that exhibits a Janus-like role: promoting malignant phenotypes in cancer cells while restraining tumor-supportive functions in non-cancerous stromal and immune cells. Meta1 is expressed in both compartments of the TME, orchestrating a dual program that supports metastasis and immune evasion. Mechanistically, we uncovered a malignancy-promoting factor (MPF) that acts as a functional ligand for Meta1, selectively enhancing pro-invasive signaling in cancer cells. We further identify Meta1 as an unconventional G protein–coupled receptor (GPCR) that plays as an accelerator in cancer cells of the TME. Meta1 interacts with Rho-GDI and Gαq to activate RhoA-mediated cytoskeletal remodeling and amoeboid migration, facilitating metastatic dissemination. We further identify MPF binding to Meta1 initiates Gβγ signaling, elevating intracellular cAMP and activating Rap1, thereby amplifying cell motility and metastatic potential. Leveraging the Meta1–MPF interaction, we designed MPF-derived peptides that specifically bind Meta1 and serve as the basis for a novel peptide-based PROTAC, which efficiently induces degradation of Meta1 and abrogates its pro-metastatic functions. Our study unveils Meta1 as an atypical GPCR with canonical signaling capacity and topological divergence, representing a shared and targetable vulnerability that bridges cancer cell-intrinsic adaptation with extrinsic TME communication. These findings establish the Meta1–MPF axis as a compelling therapeutic target for suppressing metastasis and reprogramming the TME.
Bertrand TombalBelgium
Speaker
Impact of Relugolix versus Leuprolide on the Quality of Life of Men with Advanced Prostate Cancer: Results from the Phase 3 HERO Study (European Urology, 2023)
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Jeremy TeohHong Kong, China
Speaker
Transurethral En Bloc Resection of Bladder Tumor: Where Are We Now?There is increasing evidence that transurethral en bloc resection of bladder tumour (ERBT) could lead to better peri-operative and oncological outcomes in patients with non-muscle-invasive bladder cancer. Modified approaches of ERBT have also been proposed to expand its indications for larger bladder tumours. The quality of resection is also the key for bladder-sparing treatment for muscle-invasive bladder cancer. We foresee an exciting journey ahead for ERBT, and as a urologist, we must embrace this novel technique for the best interest of our bladder cancer patients. To Publish or not to Publish? Navigating the path to academia in urologyDoing good science is the basis for technological advancement in healthcare. However, pursuing a path to academic in urology is often tough, stressful and frustrating. In this talk, I will share with you what I have learnt throughout my 15 years of research work. I will let you know what's the best and fastest way to become a globally renowned and successful researcher. Most importantly, I will explain what it takes to develop a great team and create a positive impact in people's lives. Believe in yourself! If I can do it, so can you.SIU Lecture: Role of MISTs in Male LUTS Surgical Management (Will TUR-P/ Laser Prostatectomy be Replaced?)Transurethral resection of prostate (TURP) is the current gold standard in treating patients with benign prostatic hyperplasia. Laser prostatectomy has also been used widely especially in patients who are on anticoagulants. However, both TURP and laser prostatectomy are associated with several problems including the need of spinal / general anaesthesia and the risk of male sexual dysfunction. In the past decade, we have witnessed the introduction of multiple new technologies including Rezum, Urolift, iTind and Aquablation. in this SIU lecture, we will discuss about the technical details, as well as the pros and cons of every new technology. We will also invite you to be our jury and decide whether TURP and laser prostatectomy will be replaced in the future. Novel Intravesical Therapeutics in the Evolving Landscape of NMIBCNon-muscle-invasive bladder cancer (NMIBC) is well known to be a difficult disease to manage, with a 1-year recurrence rate of up to 61% and 5-year recurrence rate of 78%. Despite the use of intravesical BCG therapy, NMIBC patients may still experience recurrence and develop what we call BCG-unresponsive NMIBC. Conventionally, we offer upfront radical cystectomy for patients with BCG-unresponsive NMIBC, however, this is an ultra-major surgery with significant risk of complications and could also lead to significant deterioration in quality of life in the long run. We are in urgent need for novel therapies to manage this difficult condition. In this lecture, we will discuss the evidence on the different novel intravesical therapies in treating BCG-unresponsive NMIBC. SIU Lecture: Role of MISTs in Male LUTS Surgical Management (Will TUR-P/ Laser Prostatectomy be Replaced?)
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Haruki KumeJapan
Speaker
Updates on Molecular Classification and Diagnostics of Upper Urinary Tract Urothelial CarcinomaUpper urinary tract urothelial carcinoma (UTUC) is a relatively common form of urothelial cancer. However, the molecular mechanisms underlying its carcinogenesis and progression have not been well understood. Most urologists previously believed that the mutational profiles of UTUC and urothelial bladder carcinoma (UBC) were similar. In 2021, by analyzing 198 cases of upper urinary tract cancer, we identified five distinct molecular subtypes of UTUC, each characterized by unique gene expression patterns, tumor locations/histology, and clinical outcomes: hypermutated, TP53/MDM2, RAS, FGFR3, and triple-negative subtypes. Notably, the hypermutated subtype, accounting for approximately 5% of all cases, was predominantly associated with Lynch syndrome, aligning with previous reports. In contrast, UBC is known to be rarely linked to Lynch syndrome. In this plenary session, I will delve into the molecular pathogenesis of UTUC and discuss future perspectives in this field.
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Osamu UkimuraJapan
Speaker
A Fully Automated Artificial Intelligence System to Assist Pathologists' Diagnosis to Predict Histologically High-Grade Urothelial Carcinoma from Digitized Urine CytologyBackground: Urine cytology, although a useful screening method for urothelial carcinoma, lacks sensitivity. As an emerging technology, artificial intelligence (AI) improved image analysis accuracy significantly.
Objective: To develop a fully automated AI system to assist pathologists in the histological prediction of high-grade urothelial carcinoma (HGUC) from digitized urine cytology slides.
Design, setting, and participants: We digitized 535 consecutive urine cytology slides for AI use. Among these slides, 181 were used for AI development, 39 were used as AI test data to identify HGUC by cell-level classification, and 315 were used as AI test data for slide-level classification.
Outcome measurements and statistical analysis: Out of the 315 slides, 171 were collected immediately prior to bladder biopsy or transurethral resection of bladder tumor, and then outcomes were compared with the histological presence of HGUC in the surgical specimen. The primary aim was to compare AI prediction of the histological presence of HGUC with the pathologist's histological diagnosis of HGUC. Secondary aims were to compare the time required for AI evaluation and concordance between the AI's classification and pathologist's cytology diagnosis.
Results and limitations: The AI capability for predicting the histological presence of HGUC was 0.78 for the area under the curve. Comparing the AI predictive performance with pathologists' diagnosis, the AI sensitivity of 63% for histological HGUC prediction was superior to a pathologists' cytology sensitivity of 46% (p = 0.0037). On the contrary, there was no significant difference between the AI specificity of 83% and pathologists' specificity of 89% (p = 0.13), and AI accuracy of 74% and pathologists' accuracy of 68% (p = 0.08). The time required for AI evaluation was 139 s. With respect to the concordance between the AI prediction and pathologist's cytology diagnosis, the accuracy was 86%. Agreements with positive and negative findings were 92% and 84%, respectively.
Conclusions: We developed a fully automated AI system to assist pathologists' histological diagnosis of HGUC using digitized slides. This AI system showed significantly higher sensitivity than a board-certified cytopathologist and may assist pathologists in making urine cytology diagnoses, reducing their workload.
Patient summary: In this study, we present a deep learning-based artificial intelligence (AI) system that classifies urine cytology slides according to the Paris system. An automated AI system was developed and validated with 535 consecutive urine cytology slides. The AI predicted histological high-grade urothelial carcinoma from digitized urine cytology slides with superior sensitivity than pathologists, while maintaining comparable specificity and accuracy.
Keywords: Artificial intelligence; Deep learning; The Paris System; Urine cytology; Urothelial carcinoma.
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Athanasios PapatsorisGreece
Speaker
BCG Refractory Cancer: Current Status of Intravesical TreatmentRecommendations in Laser Use for the Treatment of Upper Tract Urothelial Carcinoma
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Lui Shiong LeeSingapore
Moderator
Technical Pearls: Robotic Intra-Corporeal OBSThis session will demonstrate the key steps required in the intra-corporeal creation of a Studer type orthotropic bladder substitute.
Yuki EndoJapan
Speaker
UTUC Treatment — Evidence & Guideline Recommendation "Current Status and Future Perspectives of Robot-Assisted Nephroureterectomy (RNU) in the Treatment of Upper Tract Urothelial Carcinoma (UTUC): Evidence and Guideline Recommendations"
The standard treatment for upper tract urothelial carcinoma (UTUC) is surgical therapy. With the advancement of robot-assisted surgery, robotic procedures have become widespread in both upper and lower urinary tracts. In Japan, robot-assisted laparoscopic nephroureterectomy (RNU) for UTUC was included in health insurance coverage in 2019, and the proportion of RNUs for UTUC treatment is expected to increase. RNU, supported by robotic assistance, enables minimally invasive and precise procedures, allowing for reduced postoperative complications and shorter recovery periods (O'Sullivan et al., BJUI Compass. 2023). With further accumulation of data from randomized prospective trials and long-term follow-up studies, improvements in therapeutic outcomes, such as reduced postoperative recurrence, are anticipated.
However, as a new technology, there is currently no established evidence. In a notable study, the only prospective randomized trial comparing laparoscopic nephroureterectomy (LNU) with open nephroureterectomy (ONU) showed no difference in disease-specific survival overall. However, in the pT3 or higher group, disease-specific survival and metastasis-free survival were significantly lower in the LNU group (Simone G et al., Eur Urol, 2009). Based on these results, both the European Association of Urology (EAU) guidelines and the Japanese Urological Association (JUA) guidelines recommend ONU for cT3 or higher stages.
In addition, drug therapies, including immune checkpoint inhibitors (ICIs) and antibody-drug conjugates (ADCs), are rapidly advancing, and reports of new clinical trials combining these therapies are changing the surgical strategies for MIUC. I would like to review the current positioning of RNU in each guideline and discuss cancer control points when performing RNU, which is expected to become more widespread, with the latest evidence.
TICC - 3F Banquet Hall
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