Pembrolizumab monotherapy for high-risk non-muscle-invasive bladder cancer without carcinoma in situ and unresponsive to BCG (KEYNOTE-057): a single-arm, multicentre, phase 2 trial.

BACKGROUND: The KEYNOTE-057 trial evaluated activity and safety of pembrolizumab in patients with BCG-unresponsive high-risk non-muscle-invasive bladder cancer who were ineligible for or declined radical cystectomy. In cohort A (patients with carcinoma in situ, with or without papillary tumours) of the KEYNOTE-057 study, pembrolizumab monotherapy led to a complete response rate of 41% at 3 months, and 46% of responders maintained a response lasting at least 12 months. Here, we evaluate pembrolizumab monotherapy in cohort B of patients with papillary tumours without carcinoma in situ. METHODS: KEYNOTE-057 is a single-arm, phase 2 study in 54 sites (hospitals and cancer centres) in 14 countries. Cohort B eligible patients were aged 18 years and older, had an Eastern Cooperative Oncology Group performance status of 0-2, and had BCG-unresponsive high-risk non-muscle-invasive bladder cancer with papillary tumours (high-grade Ta or any-grade T1) without carcinoma in situ. Transurethral resection of bladder tumour within 12 weeks of first pembrolizumab dose was required. Patients received pembrolizumab 200 mg intravenously every 3 weeks for a maximum of 35 cycles. Primary endpoint was 12-month disease-free survival of high-risk non-muscle-invasive bladder cancer or progressive disease as assessed by cystoscopy, cytology, and central pathology and radiology review. Activity was assessed in all patients who received at least one dose of the study drug and had a baseline evaluation. Safety was assessed in all patients who received at least one dose of the study drug. This trial is registered with ClinicalTrials.gov number, NCT02625961, and is ongoing. FINDINGS: Between April 12, 2016, and June 17, 2021, 132 patients (104 [79%] men and 28 [21%] women) who had received a median of ten (IQR 9-15) previous BCG instillations were enrolled into cohort B of the study. Patients received a median of 10 cycles (IQR 6-27) of pembrolizumab. At data cutoff date, Oct 20, 2022, median follow-up was 45·4 months (IQR 36·4-59·3) and five (4%) of 132 patients remained on treatment. The 12-month disease-free survival was 43·5% (95% CI 34·9-51·9). Treatment-related adverse events occurred in 97 (73%) of 132 patients; 19 (14%) had a grade 3 or 4 treatment-related adverse event; the most common grade 3 or 4 treatment-related adverse events were colitis (in three [2%] patients) and diarrhoea (in two [2%]). 17 (13%) of 132 patients experienced serious treatment-related adverse events, of which colitis (three patients [2%]) was most common. No treatment-related deaths occurred. INTERPRETATION: Pembrolizumab monotherapy showed antitumour activity and manageable toxicity in patients with BCG-unresponsive high-risk Ta or T1 bladder cancer without carcinoma in situ and could potentially be a suitable treatment option for patients who decline or are ineligible for radical cystectomy. Findings will need to be confirmed in a randomised controlled trial. FUNDING: Merck Sharp & Dohme.

Dynamism of andrological surgery in France: Evolution of procedures over 10 years.

INTRODUCTION: Andrology and urogenital reconstruction are emerging disciplines in French urology. The aim of our study was to evaluate the evolution of andrological surgical procedures over the period 2013-2022 using national data. MATERIALS AND METHODS: We collected national common classification of medical acts (CCAM) coding data for all procedures involving andrological surgery from the Scansanté internet platform set up by the Technical Agency for Information on Hospitalisation, which collects prospectively from healthcare structures all procedures coded according to CCAM coding. All surgical procedures in andrology were selected. The inclusion period extended from 2013 to 2022. RESULTS: In 10 years, the number of vasectomies has increased tenfold, with 29,890 cases in 2022. Vaso-vasostomies remain marginal, with 80 cases per year. Trans-identity surgeries are rising sharply. Vaginoplasties have multiplied by 4 (333 in 2022) and masculinising surgeries have multiplied by 10 (234 in 2022). Penile prosthesis surgery has increased slightly over 10 years. The number of testicular biopsies has remained stable over time, as has the number of surgeries for curvature of the penis. CONCLUSION: Two andrological surgeries are showing very strong growth: vasectomy and transgender surgery. The emergence of these 2 activities is linked to societal aspirations. Urologists need to be trained to meet this demand. NIVEAU DE PREUVE: Grade 4.

50 years of inflatable penile implants: Where do we stand in France?

INTRODUCTION: With 50 years' experience, inflatable penile implants are the preferred option for erectile dysfunction refractory to pharmacological and mechanical treatment. Technical and surgical improvements have optimized patient success and satisfaction. However, multi-factorial dissatisfaction persists. OBJECTIVE: The aim of this study is to provide an overview of available technological improvements and innovations, as well as the perioperative management and complications of inflatable penile implant surgery. METHOD: A literature review was carried out over the last twenty years to answer 4 questions: what are the different inflatable penile implants available in 2023, for which indications, results and complications. RESULTS: Four companies propose inflatable penile implants in France. The main improvements have been in the various components of the prosthesis with better cylinder extension, more ergonomic reservoirs, and more manageable pumps, leading to a better durability. Indications have been extended to patients suffering from Peyronie's disease and in emergency cases of priapism. In response to demand from the transgender population, specific phalloplasty implants have been developed. New options are being developed for difficult cases of retracted penis. Results show a high satisfaction rate. Currently the main challenge is the management of infection with the development of rescue protocols using antibiotics to preserve implants - or replace them in a single operation. CONCLUSION: After 50years' experience, improvements in penile implants led to effective, satisfactory and safe treatment and can be proposed in new indications. Further development is sill necessary to offer solutions in difficult cases.

Is "Kidney Stone Calculator" efficient in predicting ureteroscopic lithotripsy duration? A holmium:YAG and thulium fiber lasers comparative analysis.

PURPOSE: This study aimed to evaluate the ability of Kidney Stone Calculator (KSC), a flexible ureteroscopy surgical planning software, to predict the lithotripsy duration with both holmium:YAG (Ho:YAG) and thulium fiber laser (TFL). METHODS: A multicenter prospective study was conducted from January 2020 to April 2023. Patients with kidney or ureteral stones confirmed at non-contrast computed tomography and treated by flexible ureteroscopy with laser lithotripsy were enrolled. "Kidney Stone Calculator" provided stone volume and subsequent lithotripsy duration estimation using three-dimensional segmentation of the stone on computed tomography and the graphical user interface for laser settings. The primary endpoint was the quantitative and qualitative comparison between estimated and effective lithotripsy durations. Secondary endpoints included subgroup analysis (Ho:YAG-TFL) of differences between estimated and effective lithotripsy durations and intraoperative outcomes. Multivariate analysis assessed the association between pre- and intraoperative variables and these differences according to laser source. RESULTS: 89 patients were included in this study, 43 and 46 in Ho:YAG and TFL groups, respectively. No significant difference was found between estimated and effective lithotripsy durations (27.37 vs 28.36 min, p = 0.43) with a significant correlation (r = + 0.89, p < 0.001). Among groups, this difference did not differ (p = 0.68 and 0.07, respectively), with a higher correlation between estimated and effective lithotripsy durations for TFL compared to Ho:YAG (r = + 0.95, p < 0.001 vs r = + 0.81, p < 0.001, respectively). At multivariate analysis, the difference was correlated with preoperative (volume > 2000 mm3 (Ho:YAG), 500-750 mm3 SV and calyceal diverticulum (TFL)), operative (fragmentation setting (p > 0.001), and basket utilization (p = 0.05) (Ho:YAG)) variables. CONCLUSION: KSC is a reliable tool for predicting the lithotripsy duration estimation during flexible ureteroscopy for both Ho:YAG and TFL. However, some variables not including laser source may lead to underestimating this estimation.

Chatbots vs andrologists: Testing 25 clinical cases.

OBJECTIVE: AI-derived language models are booming, and their place in medicine is undefined. The aim of our study is to compare responses to andrology clinical cases, between chatbots and andrologists, to assess the reliability of these technologies. MATERIAL AND METHOD: We analyzed the responses of 32 experts, 18 residents and three chatbots (ChatGPT v3.5, v4 and Bard) to 25 andrology clinical cases. Responses were assessed on a Likert scale ranging from 0 to 2 for each question (0-false response or no response; 1-partially correct response, 2- correct response), on the basis of the latest national or, in the absence of such, international recommendations. We compared the averages obtained for all cases by the different groups. RESULTS: Experts obtained a higher mean score (m=11/12.4 σ=1.4) than ChatGPT v4 (m=10.7/12.4 σ=2.2, p=0.6475), ChatGPT v3.5 (m=9.5/12.4 σ=2.1, p=0.0062) and Bard (m=7.2/12.4 σ=3.3, p<0.0001). Residents obtained a mean score (m=9.4/12.4 σ=1.7) higher than Bard (m=7.2/12.4 σ=3.3, p=0.0053) but lower than ChatGPT v3.5 (m=9.5/12.4 σ=2.1, p=0.8393) and v4 (m=10.7/12.4 σ=2.2, p=0.0183) and experts (m=11.0/12.4 σ=1.4,p=0.0009). ChatGPT v4 performance (m=10.7 σ=2.2) was better than ChatGPT v3.5 (m=9.5, σ=2.1, p=0.0476) and Bard performance (m=7.2 σ=3.3, p<0.0001). CONCLUSION: The use of chatbots in medicine could be relevant. More studies are needed to integrate them into clinical practice.

Artificial Intelligence: Ready To Pass the European Board Examinations in Urology?

The role of artificial intelligence (AI) in the medical domain is increasing on an annual basis. AI allows instant access to the latest scientific data in urological surgery, facilitating a level of theoretical knowledge that previously required several years of practice and training. To evaluate the capability of AI to provide robust data in a specialized domain, we submitted the in-service assessment of the European Board of Urology to three different AI tools: ChatGPT 3.5, ChatGPT 4.0, and Bard. The assessment consists of 100 single-answer questions with four multiple-choice options. We compared the responses of 736 participants to the AI responses. The average score for the 736 participants was 67.20. ChatGPT 3.5 scored 59 points, ranking in 570th place. ChatGPT 4.0 scored 80 points, ranking 80th, just on the border of the top 10%. Google Bard scored 68 points, ranking 340th. Our study demonstrates that AI systems have the capability to participate in a urological examination and achieve satisfactory results. However, a critical perspective must be maintained, as current AI systems are not infallible. Finally, the role of AI in the acquisition of knowledge and the dissemination of information remains to be delineated. Patient summary: We submitted questions from the European Diploma in Urological Surgery to three artificial intelligence (AI) systems. Our findings reveal that AI tools show remarkable performance in assessments of urological surgical knowledge. However, certain limitations were also observed.

Proteogenomic Characterization of Bladder Cancer Reveals Sensitivity to Apoptosis Induced by Tumor Necrosis Factor-related Apoptosis-inducing Ligand in FGFR3-mutated Tumors.

BACKGROUND: Molecular understanding of muscle-invasive (MIBC) and non-muscle-invasive (NMIBC) bladder cancer is currently based primarily on transcriptomic and genomic analyses. OBJECTIVE: To conduct proteogenomic analyses to gain insights into bladder cancer (BC) heterogeneity and identify underlying processes specific to tumor subgroups and therapeutic outcomes. DESIGN, SETTING, AND PARTICIPANTS: Proteomic data were obtained for 40 MIBC and 23 NMIBC cases for which transcriptomic and genomic data were already available. Four BC-derived cell lines harboring FGFR3 alterations were tested with interventions. INTERVENTION: Recombinant tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), second mitochondrial-derived activator of caspases mimetic (birinapant), pan-FGFR inhibitor (erdafitinib), and FGFR3 knockdown. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Proteomic groups from unsupervised analyses (uPGs) were characterized using clinicopathological, proteomic, genomic, transcriptomic, and pathway enrichment analyses. Additional enrichment analyses were performed for FGFR3-mutated tumors. Treatment effects on cell viability for FGFR3-altered cell lines were evaluated. Synergistic treatment effects were evaluated using the zero interaction potency model. RESULTS AND LIMITATIONS: Five uPGs, covering both NMIBC and MIBC, were identified and bore coarse-grained similarity to transcriptomic subtypes underlying common features of these different entities; uPG-E was associated with the Ta pathway and enriched in FGFR3 mutations. Our analyses also highlighted enrichment of proteins involved in apoptosis in FGFR3-mutated tumors, not captured through transcriptomics. Genetic and pharmacological inhibition demonstrated that FGFR3 activation regulates TRAIL receptor expression and sensitizes cells to TRAIL-mediated apoptosis, further increased by combination with birinapant. CONCLUSIONS: This proteogenomic study provides a comprehensive resource for investigating NMIBC and MIBC heterogeneity and highlights the potential of TRAIL-induced apoptosis as a treatment option for FGFR3-mutated bladder tumors, warranting a clinical investigation. PATIENT SUMMARY: We integrated proteomics, genomics, and transcriptomics to refine molecular classification of bladder cancer, which, combined with clinical and pathological classification, should lead to more appropriate management of patients. Moreover, we identified new biological processes altered in FGFR3-mutated tumors and showed that inducing apoptosis represents a new potential therapeutic option.

Immune checkpoints are predominantly co-expressed by clonally expanded CD4+FoxP3+ intratumoral T-cells in primary human cancers.

BACKGROUND: In addition to anti-PD(L)1, anti-CTLA-4 and anti-LAG-3, novel immune checkpoint proteins (ICP)-targeted antibodies have recently failed to demonstrate significant efficacy in clinical trials. In these trials, patients were enrolled without screening for drug target expression. Although these novel ICP-targeted antibodies were expected to stimulate anti-tumor CD8 + T-cells, the rationale for their target expression in human tumors relied on pre-clinical IHC stainings and transcriptomic data, which are poorly sensitive and specific techniques for assessing membrane protein expression on immune cell subsets. Our aim was to describe ICP expression on intratumoral T-cells from primary solid tumors to better design upcoming neoadjuvant cancer immunotherapy trials. METHODS: We prospectively performed multiparameter flow cytometry and single-cell RNA sequencing (scRNA-Seq) paired with TCR sequencing on freshly resected human primary tumors of various histological types to precisely determine ICP expression levels within T-cell subsets. RESULTS: Within a given tumor type, we found high inter-individual variability for tumor infiltrating CD45 + cells and for T-cells subsets. The proportions of CD8+ T-cells (~ 40%), CD4+ FoxP3- T-cells (~ 40%) and CD4+ FoxP3+ T-cells (~ 10%) were consistent across patients and indications. Intriguingly, both stimulatory (CD25, CD28, 4-1BB, ICOS, OX40) and inhibitory (PD-1, CTLA-4, PD-L1, CD39 and TIGIT) checkpoint proteins were predominantly co-expressed by intratumoral CD4+FoxP3+ T-cells. ScRNA-Seq paired with TCR sequencing revealed that T-cells with high clonality and high ICP expressions comprised over 80% of FoxP3+ cells among CD4+ T-cells. Unsupervised clustering of flow cytometry and scRNAseq data identified subsets of CD8+ T-cells and of CD4+ FoxP3- T-cells expressing certain checkpoints, though these expressions were generally lower than in CD4+ FoxP3+ T-cell subsets, both in terms of proportions among total T-cells and ICP expression levels. CONCLUSIONS: Tumor histology alone does not reveal the complete picture of the tumor immune contexture. In clinical trials, assumptions regarding target expression should rely on more sensitive and specific techniques than conventional IHC or transcriptomics. Flow cytometry and scRNAseq accurately characterize ICP expression within immune cell subsets. Much like in hematology, flow cytometry can better describe the immune contexture of solid tumors, offering the opportunity to guide patient treatment according to drug target expression rather than tumor histological type.

Cohort profile: COBLAnCE: a French prospective cohort to study prognostic and predictive factors in bladder cancer and to generate real-world data on treatment patterns, resource use and quality of life.

PURPOSE: Bladder cancer is a complex disease with a wide range of outcomes. Clinicopathological factors only partially explain the variability between patients in prognosis and treatment response. There is a need for large cohorts collecting extensive data and biological samples to: (1) investigate gene-environment interactions, pathological/molecular classification and biomarker discovery; and (2) describe treatment patterns, outcomes, resource use and quality of life in a real-world setting. PARTICIPANTS: COBLAnCE (COhort to study BLAdder CancEr) is a French national prospective cohort of patients with bladder cancer recruited between 2012 and 2018 and followed for 6 years. Data on patient and tumour characteristics, treatments, outcomes and biological samples are collected at enrolment and during the follow-up. FINDINGS TO DATE: We describe the cohort at enrolment according to baseline surgery and tumour type. In total, 1800 patients were included: 1114 patients with non-muscle-invasive bladder cancer (NMIBC) and 76 patients with muscle-invasive bladder cancer (MIBC) had transurethral resection of a bladder tumour without cystectomy, and 610 patients with NMIBC or MIBC underwent cystectomy. Most patients had a solitary lesion (56.3%) without basement membrane invasion (71.7% of Ta and/or Tis). Half of the patients with cystectomy were stage ≤T2 and 60% had non-continent diversion. Surgery included local (n=298) or super-extended lymph node dissections (n=11) and prostate removal (n=492). Among women, 16.5% underwent cystectomy and 81.4% anterior pelvectomy. FUTURE PLANS: COBLAnCE will be used for long-term studies of bladder cancer with focus on clinicopathological factors and molecular markers. It will lead to a much-needed improvement in the understanding of the disease. The cohort provides valuable real-world data, enabling researchers to study various research questions, assess routine medical practices and guide medical decision-making.

Clinical Reproducibility of the Stone Volume Measurement: A "Kidney Stone Calculator" Study.

BACKGROUND: An accurate estimation of the stone burden is the key factor for predicting retrograde intra-renal surgical outcomes. Volumetric calculations better stratify stone burden than linear measurements. We developed a free software to assess the stone volume and estimate the lithotrity duration according to 3D-segmented stone volumes, namely the Kidney Stone Calculator (KSC). The present study aimed to validate the KSC's reproducibility in clinical cases evaluating its inter-observer and intra-observer correlations. METHODS: Fifty patients that harbored renal stones were retrospectively selected from a prospective cohort. For each patient, three urologists with different experience levels in stone management made five measurements of the stone volume on non-contrast-enhanced computed tomography (NCCT) images using the KSC. RESULTS: the overall inter-observer correlation (Kendall's concordance coefficient) was 0.99 (p < 0.0001). All three paired analyses of the inter-observer reproducibility were superior to 0.8. The intra-observer variation coefficients varied from 4% to 6%, and Kendall's intra-observer concordance coefficient was found to be superior to 0.98 (p < 0.0001) for each participant. Subgroup analyses showed that the segmentation of complex stones seems to be less reproductible. CONCLUSIONS: The Kidney Stone Calculator is a reliable tool for the stone burden estimation. Its extension for calculating the lithotrity duration is of major interest and could help the practitioner in surgical planning.

A Case-Only Genome-Wide Interaction Study of Smoking and Bladder Cancer Risk: Results from the COBLAnCE Cohort.

Bladder cancer (BC) is the 6th most common cancer worldwide, with tobacco smoking considered as its main risk factor. Accumulating evidence has found associations between genetic variants and the risk of BC. Candidate gene-environment interaction studies have suggested interactions between cigarette smoking and NAT2/GSTM1 gene variants. Our objective was to perform a genome-wide association case-only study using the French national prospective COBLAnCE cohort (COhort to study BLAdder CancEr), focusing on smoking behavior. The COBLAnCE cohort comprises 1800 BC patients enrolled between 2012 and 2018. Peripheral blood samples collected at enrolment were genotyped using the Illumina Global Screening Array with a Multi-Disease drop-in panel. Genotyping data (9,719,614 single nucleotide polymorphisms (SNP)) of 1674, 1283, and 1342 patients were analyzed for smoking status, average tobacco consumption, and age at smoking initiation, respectively. A genome-wide association study (GWAS) was conducted adjusting for gender, age, and genetic principal components. The results suggest new candidate loci (4q22.1, 12p13.1, 16p13.3) interacting with smoking behavior for the risk of BC. Our results need to be validated in other case-control or cohort studies.

Late complications and 5 years outcomes of robotic partial nephrectomy in France: prospective assessment in the French Kidney Cancer Research Network (UroCCR 10).

PURPOSE: To describe the practice of robotic-assisted partial nephrectomy (RAPN) in France and prospectively assess the late complications and long-term outcomes. METHODS: Prospective, multicenter (n = 16), observational study including all patients diagnosed with a renal tumor who underwent RAPN. Preoperative, intraoperative, postoperative, and follow-up data were collected and stored in the French research network for kidney cancer database (UroCCR). Patients were included over a period of 12 months, then followed for 5 years. RESULTS: In total, 466 patients were included, representing 472 RAPN. The mean tumor size was 3.4 ± 1.7 cm, most of moderate complexity (median PADUA and RENAL scores of 8 [7-10] and 7 [5-9]). Indication for nephron-sparing surgery was relative in 7.1% of cases and imperative in 11.8%. Intraoperative complications occurred in 6.8% of patients and 4.2% of RAPN had to be converted to open surgery. Severe postoperative complications were experienced in 2.3% of patients and late complications in 48 patients (10.3%), mostly within the first 3 months and mainly comprising vascular, infectious, or parietal complications. At 5 years, 29 patients (6.2%) had chronic kidney disease upstaging, 21 (4.5%) were diagnosed with local recurrence, eight (1.7%) with contralateral recurrence, 25 (5.4%) with metastatic progression, and 10 (2.1%) died of the disease. CONCLUSION: Our results reflect the contemporary practice of French expert centers and is, to our knowledge, the first to provide prospective data on late complications associated with RAPN. We have shown that RAPN provides good functional and oncologic outcomes while limiting short- and long-term morbidity. TRIAL REGISTRATION: NCT03292549.

Polyploid Giant Cancer Cells Are Frequently Found in the Urine of Prostate Cancer Patients.

Prostate cancer is the third cause of cancer-related deaths in men. Its early and reliable diagnosis is still a public health issue, generating many useless prostate biopsies. Prostate cancer cells detected in urine could be the target of a powerful test but they are considered too rare. By using an approach targeting rare cells, we have analyzed urine from 45 patients with prostate cancer and 43 healthy subjects under 50 y.o. We observed a relevant number of giant cells in patients with cancer. Giant cells, named Polyploid Giant Cancer Cells (PGCC), are thought to be involved in tumorigenesis and treatment resistance. We thus performed immune-morphological studies with cancer-related markers such as α-methylacyl-CoA racemase (AMACR), prostate-specific membrane antigen (PSMA), and telomerase reverse transcriptase (TERT) to understand if the giant cells we found are PGCC or other urinary cells. We found PGCC in the urine of 22 patients, including those with early-stage prostate cancer, and one healthy subject. Although these results are preliminary, they provide, for the first time, clinical evidence that prostate cancers release PGCC into the urine. They are expected to stimulate further studies aimed at understanding the role of urinary PGCC and their possible use as a diagnostic tool and therapeutic target.

Artificial intelligence to improve cytology performance in urothelial carcinoma diagnosis: results from validation phase of the French, multicenter, prospective VISIOCYT1 trial.

PURPOSE: Cytology and cystoscopy, the current gold standard for diagnosing urothelial carcinomas, have limits: cytology has high interobserver variability with moderate or not optimal sensitivity (particularly for low-grade tumors); while cystoscopy is expensive, invasive, and operator dependent. The VISIOCYT1 study assessed the benefit of VisioCyt® for diagnosing urothelial carcinoma. METHODS: VISIOCYT1 was a French prospective clinical trial conducted in 14 centers. The trial enrolled adults undergoing endoscopy for suspected bladder cancer or to explore the lower urinary tract. Participants were allocated either Group 1: with bladder cancer, i.e., with positive cystoscopy or with negative cystoscopy but positive cytology, or Group 2: without bladder cancer. Before cystoscopy and histopathology, slides were prepared for cytology and the VisioCyt® test from urine samples. The diagnostic performance of VisioCyt® was assessed using sensitivity (primary objective, 70% lower-bound threshold) and specificity (75% lower-bound threshold). Sensitivity was also assessed by tumor grade and T-staging. VisioCyt® and cytology performance were evaluated relative to the histopathological assessments. RESULTS: Between October 2017 and December 2019, 391 participants (170 in Group 1 and 149 in Group 2) were enrolled. VisioCyt®'s sensitivity was 80.9% (95% CI 73.9-86.4%) and specificity was 61.8% (95% CI 53.4-69.5%). In high-grade tumors, the sensitivity was 93.7% (95% CI 86.0-97.3%) and in low-grade tumors 66.7% (95% CI 55.2-76.5%). Sensitivity by T-staging, compared to the overall sensitivity, was higher in high-grade tumors and lower in low-grade tumors. CONCLUSION: VisioCyt® is a promising diagnostic tool for urothelial cancers with improved sensitivities for high-grade tumors and notably for low-grade tumors.

[Penile necrosis, a specific complication of prostatic artery embolization]. / Nécrose pénienne, une complication spécifique de l'embolisation prostatique.

INTRODUCTION: Endoscopic surgery is the standard treatment for benign prostatic hyperplasia (BPH) refractory to pharmacological treatments. In order to reduce invasiveness and preserve sexual function, prostatic artery embolization (PAE) has been developed. However, the technical difficulties of carrying out this procedure and the results, which have yet to be confirmed, mean that it is not currently recommended. The seriousness of the complications generated should lead to a reflection on the benefit-risk balance. The objective is to report a case of penile ischemia after embolization of the prostatic arteries. MATERIAL AND METHOD: A severe complication following prostatic artery embolization (PAE) is reported with its clinical and paraclinical evaluation before and after the procedure as well as the therapeutic management. RESULTS: Penile necrosis following prostatic artery embolization was reported in a 75-year-old patient despite an attempt of deobstruction. Lower urinary tract symptoms worsened postoperatively, associated with glans necrosis and refractory erectile dysfunction. CONCLUSION: The place of PAE in the therapeutic arsenal of BPH needs to be confirmed. This innovative technique exposes the patient to potentially severe risks such as penile ischemia, not encountered in conventional endoscopic surgical treatment. PAE should not be included in the therapeutic armamentarium for BPH outside of clinical trials.

PET Imaging in Bladder Cancer: An Update and Future Direction.

Molecular imaging with positron emission tomography is a powerful tool in bladder cancer management. In this review, we aim to address the current place of the PET imaging in bladder cancer care and offer perspectives on potential future radiopharmaceutical and technological advancements. A special focus is given to the following: the role of [18F] 2-[18F]fluoro-2-deoxy-D-glucose positron emission tomography in the clinical management of bladder cancer patients, especially for staging and follow-up; treatment guided by [18F]FDG PET/CT; the role of [18F]FDG PET/MRI, the other PET radiopharmaceuticals beyond [18F]FDG, such as [68Ga]- or [18F]-labeled fibroblast activation protein inhibitor; and the application of artificial intelligence.

Treatment of muscle-invasive urothelial cancer with nivolumab (CheckMate 274 study): a plain language summary.

WHAT IS THIS SUMMARY ABOUT?: This is a summary of a paper published in a medical journal that describes the results of a study called CheckMate 274. This study looked at a new treatment for muscle-invasive urothelial cancer, a type of cancer found in the urinary tract that has spread from the inner lining of the urinary tract or bladder and into the surrounding muscle wall where it can then spread to other parts of the body. The standard treatment for muscle-invasive urothelial cancer is surgery to remove affected parts of the urinary tract. However, cancer returns in more than half of people after this surgery. Adjuvant therapy is given to people after surgery with muscle-invasive urothelial cancer with a goal to reduce the risk of the cancer coming back; however, at the time this study started, there was no standard adjuvant treatment. WHAT HAPPENED IN THE STUDY?: In the CheckMate 274 study, researchers compared nivolumab with a placebo as an adjuvant treatment for people with muscle-invasive urothelial cancer. The aim of the study was to understand how well nivolumab worked to reduce the chance of the cancer returning after surgery. The study also looked at what side effects (unwanted or unexpected results or conditions that are possibly related to the use of a medication) people had with treatment. WHAT DO THE RESULTS MEAN?: The results showed that people who received nivolumab versus placebo: Survived longer before the cancer was detected again, including people who had programmed death ligand-1 (shortened to PD-L1) on their cancer cells. Survived longer before a secondary cancer outside of the urinary tract was detected. Experienced no differences in health-related quality of life (the impact of the treatment on a person's mental and physical health). Had similar side effects to the people who received nivolumab in other studies. Clinical Trial Registration: NCT02632409 (ClinicalTrials.gov).

Epigenomic mapping identifies an enhancer repertoire that regulates cell identity in bladder cancer through distinct transcription factor networks.

Muscle-invasive bladder cancer (BLCA) is an aggressive disease. Consensus BLCA transcriptomic subtypes have been proposed, with two major Luminal and Basal subgroups, presenting distinct molecular and clinical characteristics. However, how these distinct subtypes are regulated remains unclear. We hypothesized that epigenetic activation of distinct super-enhancers could drive the transcriptional programs of BLCA subtypes. Through integrated RNA-sequencing and epigenomic profiling of histone marks in primary tumours, cancer cell lines, and normal human urothelia, we established the first integrated epigenetic map of BLCA and demonstrated the link between subtype and epigenetic control. We identified the repertoire of activated super-enhancers and highlighted Basal, Luminal and Normal-associated SEs. We revealed super-enhancer-regulated networks of candidate master transcription factors for Luminal and Basal subgroups including FOXA1 and ZBED2, respectively. FOXA1 CRISPR-Cas9 mutation triggered a shift from Luminal to Basal phenotype, confirming its role in Luminal identity regulation and induced ZBED2 overexpression. In parallel, we showed that both FOXA1 and ZBED2 play concordant roles in preventing inflammatory response in cancer cells through STAT2 inhibition. Our study furthers the understanding of epigenetic regulation of muscle-invasive BLCA and identifies a co-regulated network of super-enhancers and associated transcription factors providing potential targets for the treatment of this aggressive disease.

Urinary biomarkers for bladder cancer diagnosis and NMIBC follow-up: a systematic review.

BACKGROUND: Bladder cancer detection and follow-up is based on cystoscopy and/or cytology, but it remains imperfect and invasive. Current research focuses on diagnostic biomarkers that could improve bladder cancer detection and follow-up by discriminating patients at risk of aggressive cancer who need confirmatory TURBT (Transurethral Resection of Bladder Tumour) from patients at no risk of aggressive cancer who could be spared from useless explorations. OBJECTIVE: To perform a systematic review of data on the clinical validity and clinical utility of eleven urinary biomarkers (VisioCyt®, Xpert®Bladder, BTA stat®, BTA TRAK™, NMP22 BC®, NMP22® BladderChek® Test, ImmunoCyt™/uCyt1+™, UroVysion Bladder Cancer Kit®, Cxbladder, ADXBLADDER, Urodiag®) for bladder cancer diagnosis and for non-muscle invasive bladder cancer (NMIBC) follow-up. METHODS: All available studies on the 11 biomarkers published between May 2010 and March 2021 and present in MEDLINE® were reviewed. The main endpoints were clinical performance for bladder cancer detection, recurrence or progression during NMIBC monitoring, and additional value compared to cytology and/or cystoscopy. RESULTS: Most studies on urinary biomarkers had a prospective design and high level of evidence. However, their results should be interpreted with caution given the heterogeneity among studies. Most of the biomarkers under study displayed higher detection sensitivity compared with cytology, but lower specificity. Some biomarkers may have clinical utility for NMIBC surveillance in patients with negative or equivocal cystoscopy or negative or atypical urinary cytology findings, and also for recurrence prediction. CONCLUSION: Urinary biomarkers might have a complementary place in bladder cancer diagnosis and NMIBC surveillance. However, their clinical benefit remains to be confirmed.