<p class="AbstractBody">The authors report the case of an 80-year-old Canadian male with a giant bladder stone who declined treatment. A bladder stone is defined as a giant bladder stone when it has a diameter greater than 4 cm or a weight greater than 100 g; they are rare, with less than 100 cases reported in the literature. These stones are even rarer in developed countries like Canada. This pathology usually requires open cystolithotomy for definitive management. To the authors’ knowledge, this is the only reported case of a patient declining treatment, which helps urologists understand the natural history of this condition through a novel growth analysis of the patient’s bladder stone.

began his session by providing a brief background on LUTS, a common complaint in an increasingly ageing male population.The objectives in assessing men with LUTS are to establish a differential diagnosis and define their clinical profile in order to assess patients' values and preferences, set their expectations, identify those at risk of progression, and provide the best evidence-based care.To provide a real-life example, Averbeck described a clinical case of a 64-yearold man with a history of benign prostatic enlargement diagnosed 10 years earlier, whose main complaint was mixed LUTS.The patient presented with bothersome urinary urgency, with a urinary frequency of 15 times a day and 2-3 times a night.The patient also had co-morbid systemic arterial hypertension, managed with losartan 50 mg/day.

Androgen deprivation therapy (ADT) has been a cornerstone in the treatment of advanced prostate cancer (PCa) for many years, and continues to form the basis of current therapeutic approaches. However, a recent dramatic upsurge in the number of treatment options available in this area creates a responsibility for healthcare professionals to carefully select optimal drugs and combinations of drugs, to ensure the best outcomes and greatest quality of life for all patients. This requires a thorough understanding of clinical trial data, and an ability to apply this knowledge to everyday clinical practice. This article summarises presentations delivered during a symposium held on 29ᵗʰ November 2023 at the Global Congress on Prostate Cancer (PROSCA) 2023 in Málaga, Spain, where three distinguished speakers described and explored practical approaches to the use of ADT in complex clinical scenarios. Nazareno Suardi, Associate Professor of Urology at the University of Brescia, Italy, described approaches to manage ADT prescription when a patient presents with cardiovascular (CV) risk factors. Matthias Saar, Director and Chairman of the Department of Urology and Uro-oncology at the University Hospital Aachen, Germany, explored whether intermittent ADT remains an alternative in the new era of hormonal therapy. Alison Birtle, Consultant Clinical Oncologist at the Rosemere Cancer Centre, Lancashire Teaching Hospitals NHS Trust, Preston, UK, investigated the importance of drug choice in triplet or doublet therapy in patients with metastatic hormone-sensitive PCa (mHSPC). The meeting was chaired by Antoni Vilaseca, Senior Specialist in the Urology Service at the Hospital Clinic, University of Barcelona, Spain, who introduced the symposium, and also co-ordinated a question and answer session to conclude the meeting.

THIS YEAR, the vibrant French capital provided the backdrop for Europe's biggest urological event, with over 10,000 attendees travelling to Paris for the 39 th European Association of Urology (EAU) Congress. Featuring talks by nearly 1,000 speakers from 124 countries, EAU24 offered a packed 4-day programme, with live surgeries, state-of-the-art lectures, and insightful case discussions and debates on cutting-edge science. The EAU Secretary General, Arnulf Stenzl, extended a warm welcome to all congress attendees in the opening ceremony, which featured a dazzling performance by the Parisian cabaret dance show. He began by highlighting the importance of collaboration in urology, acknowledging that the success of EAU would not be possible without teamwork. Stenzl also noted that the time and effort of devoted individuals is equally valuable to the field of urology, and every year, EAU recognises these exceptional personalities with the prestigious EAU Annual Awards. The award presentations kicked off with the introduction of two new EAU honorary members,

BACKGROUND AND AIMS Urothelial carcinoma in situ (CIS) of the bladder is an intra-epithelial, high grade, malignant neoplasm characterised by flat (non-papillary) growth, with high probability of disease progression.1,2 CIS has histologic features similar to invasive cancer and is often a precursor to and associated with invasive cancer. Molecularly, bladder cancer can be broadly categorised into luminal and basal subtypes.1-7 However, the molecular features that are unique to CIS, as compared to other high-grade lesions, including papillary Ta and T1 tumours, are underexplored. Bulk RNA expression profiling is a standard for molecularly characterising bladder cancer, and RNA-sequencing protocols utilising formalin-fixed paraffin-embedded (FFPE) tumours are well established. However, CIS presents challenges for RNA sequencing due to the inability to reliably detect, the low incidence rate, and the quality of RNA derived from FFPE samples. While enhanced cystoscopy and narrow band imaging have improved the ability to detect CIS, sampling acquisition techniques still limit the optimisation of RNA sequencing. Furthermore, the authors determined that established dual nucleic acid extraction protocols for FFPE samples were not feasible due to small biopsy sample sizes, and that protocols should be optimised for either RNA or DNA. This study attempts to overcome above stated challenges to understand the molecular landscape of CIS by contrasting against papillary tumours and normal urothelium using RNA-sequencing on FFPE samples, as well as whole exome sequencing, and immunohistochemical and immunofluorescent analyses, with an intent to identify unique molecular signatures associated with CIS. MATERIALS AND METHODS The authors performed whole transcriptome profiling with RNA sequencing of FFPE specimens from 15 CIS, nine high-grade papillary Ta/T1 tumours, and eight normal urothelial samples (Cohort A). Wilcoxon test was used to filter differentially expressed genes and The Cancer Genome Atlas (TCGA) single sample classifier was used to assign molecular subtypes. Whole exome sequencing was performed for 19 patients with matched CIS and papillary tumour samples (Cohort B). Using multiplex immunofluorescence and immunohistochemistry analyses, 24 samples from 15 patients were analysed for the presence of cytotoxic T cells, T helper cells, regulatory T cells, B cells, M1 and M2 macrophages, and programmed cell death protein 1 and programmed death-ligand 1-expressing cells. RESULTS The authors performed molecular subtyping applying the UROMOL classification and as previously shown for CIS, the majority were Class 2a and 2b, with four Class 3 and one Class 1. They applied the TCGA single patient classifier and the majority were luminal with a breakdown of two luminal, five luminal infiltrated, seven luminal papillary, three basal, and one neuronal subtype (Figure 1). A 46-gene signature of differentially expressed genes in CIS samples was identified and included known druggable targets that were selectively upregulated (MTOR, TYK2, AXIN1, CPT1B, GAK, and PIEZO1) or downregulated (BRD2 and NDUFB2; p&lt;0.05). An independent dataset was used to assess the robustness of these markers. High expression of MTOR, GUSBP11, KMT2D, and URB1 was significantly associated with CIS in this independent dataset.Additionally, mutational analysis of 34 matched CIS and 33 papillary tumours revealed a clonal origin of the lesions with mutations shared between both synchronous and metachronous tumours. Inter- and intra-patient mutational heterogeneity was also observed. The most frequently mutated gene was KDM6A, which was observed in 53% of the patient samples. Analysis of the immunological landscape of 24 CIS and papillary tumour lesions showed higher levels of immune cells in stromal compartments compared to carcinoma regions. Furthermore, more programmed cell death protein 1 positive cells were observed in CIS lesions compared with papillary tumours (p=0.03). CONCLUSION Collectively, this study identifies a molecular signature that distinguishes CIS lesions from papillary tumours in terms of gene expression levels, mutational landscape, and proportion of programmed cell death protein 1 positive cells that may contribute to an aggressive feature of progressive disease phenotype of the bladder cancer.