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To present a summary of the 2026 version of the European Association of Urology (EAU)-European Association of Nuclear Medicine (EANM)-European Society for Radiotherapy & Oncology (ESTRO)-European Society of Urogenital Radiology (ESUR)-International Society of Urological Pathology (ISUP)-International Society of Geriatric Oncology (SIOG) Guidelines on the treatment of relapsing, metastatic hormone-sensitive and castration-resistant prostate cancer (PCa). The Panel performed a literature review of new data, covering the time frame between 2023 and 2025. The Guidelines were updated and a strength rating for each recommendation was added based on a systematic review of the evidence. Risk stratification for relapsing PCa after primary therapy may guide salvage therapy decisions. The range of treatment options for metastatic PCa has broadened, including androgen receptor pathway inhibitors (ARPI), metastasis-directed therapy, PARP inhibitors and their combinations, as well as PSMA-based therapy. The recommendations in the EAU Guidelines are based on clinical evidence and do not account for variations in cost, reimbursement structures, or resource availability across healthcare systems. The evidence in the field of relapsing, metastatic, and castration-resistant PCa is evolving rapidly. These PCa Guidelines reflect the multidisciplinary nature of PCa management. A full version is available from the EAU Guidelines Office or online (http://uroweb.org/guideline/ prostate-cancer/).

Lung metastases in patients with metastatic rhabdomyosarcoma (RMS) have not been treated uniformly across Europe. This provides comparison of the impact of whole lung irradiation (WLI). Lung-metastatic patients included in the Cooperative Weichteilsarkom Studiengruppe-IV 2002, European Pediatric Soft Tissue Sarcoma Study Group MTS 2008 or the Soft Tissue Sarcoma Registry received four- or six-drug chemotherapy, surgery, and/or irradiation (radiotherapy) of the primary tumor. Treatment of lung lesions consisted of metastasectomy, WLI, or no local treatment according to protocols. A total of 238 patients with lung-metastatic RMS were included. Half of these patients (n = 119/238) had lung metastases only (median age, 6.6 years), mainly classified as embryonal RMS (n = 93/119, 78%). Lung-only patients underwent metastasectomy (n = 17) and/or WLI (n = 31) or no local treatment of lung metastases (n = 71). Early complete response of lung metastases was associated with favorable 3-year overall survival (p = .009). A trend toward improved event-free survival after WLI could be identified in patients ≥10 years old (hazard ratio [HR], 2.7; 95% CI, 0.8-9.6), but not in patients under 10 years old (HR, 0.86; 95% CI, 0.44-1.66). Lung-relapse-free survival (lung-RFS) was not influenced by WLI or metastasectomy in the univariable and multivariable analyses. When analyzing all lung-metastatic patients (including those with metastases in other sites, n = 238), WLI in patients older than 10 years was a significant prognostic factor (HR, 2.2; 95% CI, 1.0-4.9). The analysis failed to show a significant benefit of WLI in patients with lung-metastatic RMS, apart from the subgroup of patients older than 10 years. Lung-RFS was not influenced by WLI.

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Prostate-specific antigen (PSA) testing has been central to prostate cancer detection since FDA approval for early detection in 1994, yet its widespread application has generated enduring controversy owing to limited specificity, overdiagnosis, and the quality-of-life harms of overtreatment. Prostate cancer is among the most prevalent malignancies in men globally. Major randomized trials, including the European Randomized Study of Screening for Prostate Cancer (ERSPC), the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial, and the more recent ProtecT trial, reported divergent conclusions about prostate cancer-specific mortality benefit. International guidelines from the American Urological Association/Society of Urologic Oncology (AUA/SUO), the United States Preventive Services Task Force (USPSTF), and the European Association of Urology (EAU) differ substantially in their recommended age thresholds, screening intervals, and approaches to shared decision-making, reflecting the genuine uncertainty in the evidence base. Emerging modalities, such as multiparametric magnetic resonance imaging, serum biomarkers including the Prostate Health Index and 4Kscore, and germline genomic risk stratification, offer pathways toward more individualized screening. Polygenic risk scores and artificial intelligence-based tools show promise for integrating multiple risk factors, though most approaches remain under active investigation and require prospective validation before routine clinical deployment. This narrative review synthesizes current evidence on PSA-based screening, evaluates the principal sources of controversy, compares international guideline recommendations, and examines emerging risk-stratified approaches. Current evidence supports individualized, risk-adapted screening over universal PSA threshold application, with shared decision-making as the essential framework for integrating emerging biomarker and genomic data into clinical practice.

Metastatic urothelial cancer (mUC) is associated with diverse genomic alterations, including frequent FGFR3 mutations that influence survival outcomes and treatment responses. Erdafitinib, a targeted therapy, has shown improved survival in patients with locally advanced (LA) or mUC harbouring FGFR3 alterations, reinforcing the importance of timely FGFR3 testing. This article aims to provide practical guidance for step-by-step best practices in FGFR3 testing in mUC from sample acquisition to result reporting. This narrative review presents practical recommendations for FGFR3 testing in mUC, developed by a multidisciplinary European panel of pathologists, molecular biologists, oncologists, and urologists, based on critical appraisal of current evidence and collective clinical experience. Patients with LA/mUC should undergo FGFR3 testing at diagnosis, as supported by the current guidelines. Other factors to consider include age, frailty, fitness for treatment, and quality of life. FGFR3 testing should be performed using validated quantitative polymerase chain reaction (PCR) assays or next-generation sequencing (NGS) methods. While liquid biopsy analysis on circulating tumour deoxyribonucleic acid (ctDNA) via PCR and NGS may offer a complementary approach to tissue testing, further research is needed to determine its value in detecting FGFR3 alterations in mUC. The molecular laboratory report should contain details of all detected genetic alterations by the European Society for Medical Oncology Scale for Clinical Actionability of molecular Targets tier to indicate potential actionability. Early FGFR3 testing at diagnosis in patients with LA/mUC is clinically essential to ensure timely access to targeted therapies. Multidisciplinary collaboration is key to integrating molecular testing into patient care, supporting effective and personalised disease management.

Solid pseudopapillary neoplasm of the pancreas (SPN) is a rare low-grade malignant exocrine pancreatic tumor, mostly discovered during the second decade of life in females, with a very good prognosis, provided microscopically complete surgical excision is achieved. This manuscript presents harmonized recommendations for the diagnosis, treatment, and long-term management of pediatric SPN established by the European Cooperative Study Group for Pediatric Rare Tumors (EXPeRT) in collaboration with the European Reference Network for Pediatric Oncology (ERN PaedCan) after careful review of the literature and experts' opinions refined by selected external reviewers.

To evaluate the prognostic value of tumor size in patients with low-risk upper tract urothelial carcinoma (UTUC) undergoing radical nephroureterectomy (RNU). A retrospective multicenter European analysis was conducted on 3987 patients treated for UTUC at 17 academic institutions. After applying the exclusion criteria, 328 low-risk UTUC patients (pTaN0M0, low grade, unifocal, without hydronephrosis) were included in the analysis. Patients were stratified by tumor size in the RNU specimen: <1cm, 1-1.9cm, and &#x2265;2cm. Recurrence-free survival (RFS), cancer-specific survival (CSS), and overall survival (OS) were evaluated using Kaplan-Meier analysis. Univariable Cox regression analysis was used to evaluate the association between tumor size and disease recurrence. Because other confounding factors intrinsic to the study design were excluded, no multivariable analysis was performed. After a median follow-up of 4.2 [3.9; 4.5] years, 41 (12.5%) patients experienced disease recurrence. Kaplan-Meier analysis showed that tumors &#x2265;2cm were significantly associated with lower RFS compared to tumors of 1-1.9cm and <1cm (81% vs. 95% and 97%, respectively; P<0.05). CSS and OS did not differ significantly among groups (all P>0.05). Univariable Cox regression analysis confirmed that tumor size &#x2265;2cm was a significant predictor of disease recurrence with HR=7.18; 95%CI=[2.94-17.5]; P<0.001. Tumor size &#x2265;2cm is associated with an increased disease recurrence in low-risk UTUC. These findings align with the European Association of Urology guidelines, supporting the inclusion of tumors up to 2cm within the low-risk category.

Robot-assisted radical prostatectomy (RARP) has become a standard procedure for the surgical management of localized and locally advanced prostate cancer (PC). Surgical outcomes are closely linked to the training and experience of the operating surgeon. In 2017, the German Society for Robot-assisted Urology (DGRU) in cooperation with the working group Robotics and laparoscopy of the German Urology Society (DGU) launched a structured national curriculum designed to train new console surgeons through a standardized, competency-based educational program. This study evaluates the first five years of the curriculum, focusing on operative exposure, post-curricular activity, and perceived career impact. A structured electronic survey was distributed to all 48 participants who completed the curriculum between 2017 and 2022. Data were collected from December 2022 to February 2023 using an anonymized online questionnaire. Items included demographics, training conditions, operative volume, outcomes of RARP cases, and professional development. Descriptive statistics were generated from the anonymized dataset. Response rate was 85%, and 93% of respondents had completed the curriculum at the time of data collection. Most trainees reported substantial console exposure and institutional support during training. After graduation, approximately half of the participants had independently performed at least 100 RARPs, while 7.3% reported no complete independent procedures. The majority indicated professional advancement, increased involvement in robotic surgery, and participation in teaching. Functional and oncological outcomes were self-reported by participants and were broadly consistent with published benchmark ranges. Overall satisfaction with the curriculum was high, and participants strongly recommended the program. The first five years of the DGRU RARP curriculum demonstrate successful integration of robotic surgery into clinical practice, substantial operative activity after graduation, and positive participant-reported career development. These findings support the value of structured national training programs in complex urologic surgery.

Aging affects all organ systems, yet no standard method exists to quantify urological age. Renal function, prostate health, sexual function, fertility, and bladder control are central to men's health span, but their relationship with mental health and chronological aging remains poorly defined. The aim of this study was to develop the Urological Age and Longevity (UAL) framework, a consensus-driven composite index that quantifies urological biological age in men and explores its potential for guiding personalized strategies for healthy aging. The UAL model was constructed through a three-phase process combining literature evidence and expert consensus. First, a multidisciplinary group systematically reviewed aging and urology indices to identify relevant longevity domains. Second, the preliminary framework underwent content validation using qualitative and quantitative feedback from an expert panel. Third, each parameter was organized into consensus-defined risk tiers to create a personalized UAL score. Ten domains central to urological aging, including functional measures, biochemical markers, hormonal profile, sexual functions, systemic correlates, mental health, environmental exposures, lifestyle habits, surgical history, and family history, were identified and validated. Each parameter was assigned consensus-defined tiers, generating a structured 0 to 20 scoring system that estimates urological biological age and supports individualized risk profiling. The UAL framework is the first organ-specific biological age model in urology. It enables assessment of genitourinary aging using routine clinical and lifestyle data, offering opportunities for targeted, modifiable interventions. Prospective validation studies are now warranted to confirm its predictive and clinical utility.

To systematically evaluate the efficiency and safety of different prostate morcellators used during prostate enucleation for benign prostatic hyperplasia (BPH). A systematic review was performed according to the Preferred Reporting Items for Systematic Review and Meta-analyses guidelines. PubMed/Medline, Scopus, and Web of Science were searched for studies published between October 2012 and May 2025. Studies reporting clinical outcomes of morcellators used during prostate enucleation were included. Primary outcome was morcellation efficiency (g/min). Secondary outcomes included intraoperative complications, device malfunction, and cost when available. Risk of bias (RoB) was assessed using the Risk Of Bias In Non-randomised Studies of Interventions (ROBINS-I), RoB 2 tool, and European Association of Urology case-series criteria. Random-effects meta-analyses and multilevel meta-regression adjusted for prostate volume were conducted. A total of 22 studies comprising 5980 patients were included, most undergoing holmium laser enucleation of the prostate. The most frequently evaluated devices were the Piranha&#x2122; (Richard Wolf GmbH, Knittlingen, Germany) and Lumenis VersaCut&#x2122; (Lumenis Ltd., Yokneam, Israel; 12 and 13 studies, respectively), followed by DrillCut&#x2122; (Karl Storz SE & Co. KG, Tuttlingen, Germany), MultiCut&#x2122; (Asclepion Laser Technologies GmbH, Jena, Germany), and Cyber Blade&#x2122; (Quanta System SpA, Milan, Italy) systems. Unadjusted weighted mean morcellation efficiency was 7.80&#x2009;g/min (95% confidence interval [CI] 6.26-9.34&#x2009;g/min) for Piranha, 4.70&#x2009;g/min (95% CI 3.61-5.79&#x2009;g/min) for VersaCut, 5.90&#x2009;g/min (95% CI 3.16-8.64&#x2009;g/min) for DrillCut, and 9.59&#x2009;g/min (95% CI 4.78-14.39&#x2009;g/min) for MultiCut. In volume-adjusted meta-regression using Piranha as reference, VersaCut remained significantly less efficient (-2.75&#x2009;g/min; 95% CI -4.58 to -0.92&#x2009;g/min; P&#x2009;=&#x2009;0.003), with an even greater difference in prostates >70&#x2009;mL (-4.34&#x2009;g/min). Bladder mucosal injury was the most frequently reported complication; however, relatively rare across all devices. Meta-analysis demonstrated a significantly higher risk with VersaCut compared to Piranha (risk ratio 3.22, 95% CI 1.81-5.71), with low heterogeneity. This systematic review provides a contemporary clinical benchmark of the efficiency and safety of currently available prostate morcellators. Oscillating blade systems, particularly the Piranha morcellator, demonstrated higher morcellation efficiency and a more favourable safety profile than reciprocating blade devices, with the largest performance differences observed in patients with larger prostates.

This publication represents a summary of the updated 2026 European Association of Urology (EAU) Guidelines for nonmuscle-invasive bladder cancer (NMIBC), TaT1 and carcinoma in situ (CIS). The information presented herein is limited to urothelial carcinoma, unless specified otherwise. The aim is to provide practical recommendations on the clinical management of NMIBC, with a focus on clinical presentation. For the 2026 guidelines on NMIBC, new and relevant evidence was identified, collated, and appraised via a structured assessment of the literature. Databases searched included MEDLINE, EMBASE, and the Cochrane Library. Recommendations within the guidelines were developed by the panel to prioritise clinically important care decisions. The strength of each recommendation was determined according to a balance between desirable and undesirable consequences of alternative management strategies, the quality of the evidence (including the certainty of estimates), and the nature and variability of patient values and preferences. Key recommendations emphasise the importance of thorough diagnosis, treatment, and follow-up for patients with NMIBC. The guidelines stress the importance of defining patients' risk stratification and treating them appropriately. Key updates in the 2026 NMIBC Guidelines summary include: the addition of two new tables addressing risk factors for bladder cancer and prognostic factors for progression in subtypes; the addition of two new tables summarising the treatment options for Bacillus Calmette-Gu&#xe9;rin (BCG)-unresponsive tumours; inclusion of a new section addressing the addition of immune checkpoint inhibitors to BCG in selected high- and very high-risk NMIBC BCG-NA&#xcf;VE patients; a new table addressing the role of urinary markers in follow-up; and the addition of a new section on pragmatic de-intensification strategy for NMIBC. This overview of the 2026 EAU guidelines offers valuable insights into risk factors, diagnosis, classification, prognostic factors, treatment, and follow-up of NMIBC. They are designed for effective integration into clinical practice. The EAU has issued updated clinical practice guidelines on NMIBC. The guidelines provide recommendations for diagnosis, treatment, and follow-up, with a particular focus on quality of life for patients.

The European Association of Urology (EAU) recommends transperineal biopsy (TPBx) due to its lower infection risk and higher diagnostic rate for anterior zone tumors. This study aims to assess the learning curve of TPBx using the Perino-Flex&#xae; angle-adjustable needle guide under local anesthesia. A retrospective observational analysis was conducted from November 2023 to March 2024, involving 100 patients who underwent TPBx with coaxial technique under local anesthesia. Data collected included patient demographics, procedure and room times, pain levels, anxiety scores, and complications. The study focused on comparing procedure times, pain scores, and complication rates to evaluate the learning curve over time. The mean room time significantly decreased from 29.55 min in the first group to 19.95 min in the fifth (p < 0.001). Procedure time was reduced from 15.25 min in the first group to 7.50 min in the fifth (p < 0.001). Visual Analog Scale (VAS) scores during core sampling demonstrated a significant decrease after the first 20 patients (2.70 vs. 0.90 in the first and second quartile, respectively, p < 0.001), indicating a rapid gain in operator proficiency. When splitting the first 20 patients into two subgroups, pain scores significantly dropped after the initial 10 cases. Cancer detection rates remained stable across all groups. Notably, no infectious complications were observed throughout the study. This study highlights the learning curve for TPBx with an adjustable needle guide under local anesthesia. It shows that as experience grows, pain decreases and procedure times shorten, improving both patient comfort and efficiency. These findings offer valuable guidance for new practitioners to learn more quickly and achieve better diagnostic results.

Racial disparities in prostate cancer are well-documented, with Black men experiencing twice the mortality of White men. While prior studies suggest these disparities reflect inequitable access rather than biology, only few studies have examined this in the biochemical recurrence setting, where screening and initial treatment biases are eliminated. We compared cancer-specific mortality and other-cause mortality between non-Hispanic Black (NHB) and non-Hispanic White (NHW) men with biochemical recurrence after initial treatment. This retrospective single health system study included patients who developed BCR after radical prostatectomy or radiation therapy between 1995 and 2023. Primary outcome was cancer-specific mortality. Fine-Gray competing risk models assessed race-CSM association, stratified by treatment and adjusted for European Association of Urology biochemical recurrence risk classification. Among 968 patients (431 NHB, 44.5%; 537 NHW, 55.5%), median follow-up was 5.5 years from biochemical recurrence. Other-cause mortality was similar (Gray's test p&#x2009;=&#x2009;0.35 radical prostatectomy, p&#x2009;=&#x2009;0.41 radiation therapy). Ten-year cancer-specific mortality estimates were similar after radical prostatectomy (6.7% both races; NHB versus NHW HR 0.91, 95% CI 0.49-1.71, p&#x2009;=&#x2009;0.8) and radiation therapy (NHB 26.7% versus NHW 32.4%; HR 0.71, 95% CI 0.44-1.14, p&#x2009;=&#x2009;0.16). Limitations include single-center design and retrospective methodology. In this racially diverse single-center cohort, we found no racial disparities in cancer-specific mortality or other-cause mortality after biochemical recurrence. These findings support that racial disparities reflect modifiable access barriers rather than biological differences, emphasizing the importance of equitable care delivery.

The European Thoracic Oncology Platform (ETOP) International Breast Cancer Study Group (IBCSG) Partners Foundation initiated a series of workshops for experts to review current evidence and offer recommendations to guide future antibody-drug conjugate (ADC) research. Here, we summarise key findings from the third workshop, which included experts in various solid tumours, basic/translational research scientists and pharmaceutical industry representatives. Recent positive phase III trial data have further incorporated ADCs into the standard of care [e.g. lung: sacituzumab tirumotecan; breast: trastuzumab deruxtecan (T-DXd), sacituzumab govitecan, datopotamab deruxtecan; muscle-invasive bladder cancer: enfortumab vedotin; ovarian cancer: mirvetuximab soravastine; cervical cancer: tisotumab vedotin]. Thus, research priorities must be tailored according to tumour type, potentially focussing initially on settings where ADCs could replace chemotherapy. Many phase III ADC trials have been initiated based on positive phase I data and although these trials are larger than those conducted historically, prespecified criteria (e.g. patient numbers and magnitude of efficacy) should be met to justify proceeding directly to phase III. Importantly, although several ADCs have been successfully developed without mandatory biomarker selection, biomarker-driven ADC development enables rational patient selection, as illustrated by multiple ADCs (e.g. T-DXd, mirvetuximab soravtansine and telisotuzumab vedotin). The identification, development and validation of predictive biomarkers are therefore essential, particularly given several critical nuances, including the algorithms used to assess biomarker status and the type of specimen analysed, all of which may be influenced by temporal and spatial heterogeneity. Additional ADC research priorities include the optimisation of ADC constructs to enhance efficacy/tolerability and the identification of reliable ADC targets, including work to elucidate attributes of already-identified targets. Finally, considering the vast amount of ADC-related data being generated, artificial intelligence could be leveraged to analyse combined datasets and generate composite biomarkers, including tumour histology, optimal target expression thresholds, molecular alterations and activated pathways affecting payload activity and target function, to accelerate research.

Objectives: To assess the prevalence of high-risk human papillomavirus (hrHPV) infection and selected genitourinary pathogens and to examine their co-detection patterns in sexually active adolescent females. Methods: In this single-center cross-sectional study, 167 consecutive outpatients aged 13-17 years with self-reported sexual initiation underwent multi-pathogen polymerase chain reaction (PCR) testing for hrHPV, Chlamydia trachomatis (CT), Ureaplasma urealyticum (UU), Ureaplasma parvum (UP), and Mycoplasma genitalium (MG). Prevalence estimates are reported with 95% confidence intervals (CIs). Associations with hrHPV positivity were explored using univariable and parsimonious multivariable logistic regression; sensitivity analyses examined alternative age parameterization and exclusion of sparse variables. Results: The prevalence of hrHPV was 28.1% (47/167; 95% CI: 21.5-35.6). The prevalence of CT, UU, UP, and MG was 3.0%, 28.1%, 25.1%, and 0.6%, respectively. Any bacterial pathogen was detected in 61/167 participants (36.5%), while hrHPV-bacterial co-detection was observed in 24/167 (14.4%). In univariable analysis, UU was associated with hrHPV positivity (OR 2.55, 95% CI: 1.24-5.24; p = 0.013); this signal remained in the primary multivariable model (adjusted OR 2.46, 95% CI: 1.07-5.93; p = 0.035). A graded increase in hrHPV positivity was observed with increasing bacterial burden (p for trend = 0.018). Conclusions: Sexually active adolescent girls attending gynecologic outpatient care showed a substantial burden of hrHPV and bacterial genitourinary pathogen detection. This Central and Eastern European adolescent outpatient cohort contributes integrated multi-pathogen PCR-based epidemiologic data from a clinically relevant and underreported population. An exploratory association between UU and hrHPV positivity was observed; this signal is best interpreted as reflecting shared sexual exposure or the cervicovaginal microbial milieu rather than as evidence of an independent causal role for UU. The absence of vaccination status, behavioral, and longitudinal data represents a principal limitation. Prospective studies incorporating these variables are needed to clarify the epidemiology of hrHPV and co-detected pathogens in adolescents.

To evaluate outcomes of FT (HIFU or cryotherapy) in prostate cancer (PCa) patients who do not meet the ideal focal therapy candidate profile, assessing whether expanding selection criteria beyond traditional parameters is safe. A retrospective analysis was performed on 282 patients treated with FT for ISUP 1 and 2 PCa at a single European center (2009-2020). Patients were categorized into three groups: G1 (ideal candidates: single lesion &#x2264;12mm, favorable biopsy features), G2 (ISUP 1 with minor deviations), and G3 (ISUP 2 with multiple lesions, larger tumor size, or positive cores outside the target zone). A secondary exploratory analysis compared ISUP 2 patients fully meeting criteria versus those with one deviating feature. Multivariable regression with propensity score matching was applied. Overall recurrence occurred in 187 patients (66%): 77% in G1, 60% in G2, and 77% in G3. No significant differences were observed between G1 and G3 regarding infield recurrence-free survival, clinically significant infield recurrence-free survival, or outfield recurrence-free survival (all p>0.05). In the secondary analysis, lesion size &#x2265;12mm was the only feature associated with worse infield recurrence-free survival (p=0.04) and clinically significant infield recurrence-free survival (p=0.001). Multivariate Cox regression confirmed lesion size as an independent predictor (HR: 1.21; 95% CI: 1.05-1.40; p=0.01). Expanding FT selection criteria to include selected ISUP 2 patients with features outside traditional parameters appears safe. These preliminary findings highlight the need for multicenter studies to validate these results.

Active surveillance (AS) is a well-established strategy for managing prostate cancer (PCa); however, available evidence indicates that approximately 28% of patients may experience progression within the first 5 years. Magnetic resonance imaging (MRI) may help optimize patient selection. This study assessed whether the presence of focal lesions (prostate imaging reporting and data system (PI-RADS) &#x2265; 3) on baseline MRI is associated with an increased risk of histological progression and AS discontinuation. We conducted a retrospective study of consecutive patients enrolled in AS at a comprehensive cancer center since 2012, recorded in the Urodata platform, based on a prospectively maintained cohort and including patients meeting European Association of Urology (EAU) criteria for low- or favorable intermediate-risk PCa. Inclusion criteria were diagnostic and confirmatory transperineal biopsies performed with the institution's standard technique, available baseline MRI, and a minimum follow-up of one year. Patients with prior treatment were excluded. Histological progression was defined as an increase in Gleason grade group on follow-up biopsy compared with baseline. Progression at 5 years was evaluated using Kaplan-Meier curves and multivariable Cox proportional hazards models. Patients with PI-RADS &#x2265; 3 were classified as visible lesions on MRI (MRI+), and those with PI-RADS <3 as no visible lesions on MRI (MRI-). A total of 105 patients were included, with a median age of 64 years (interquartile range (IQR) 59-70) and a median prostate-specific antigen (PSA) of 5.8 ng/mL (IQR 4.7-8.9). The median interval between initial and confirmatory biopsy was 24 months, and median follow-up was 6 years. Seventy-one patients were classified as MRI+. Baseline characteristics were similar between groups. Five-year progression-free survival was 41% in MRI+ versus 77% in MRI- groups (hazard ratios (HR) 5.5; 95% confidence interval (CI) 2.3-13). Only 28% of patients with PI-RADS 5 remained free of progression at 5 years. Baseline PSA >6 ng/mL and PSA density >0.2 were independently associated with histological progression. The presence of PI-RADS &#x2265; 3 lesions on baseline MRI is significantly associated with an increased risk of histological progression and AS discontinuation. MRI may be a key tool for optimizing candidate selection for AS.

Bladder cancer ranks among the most common malignancies worldwide, with urothelial carcinoma as the predominant histological type. Its development from normal urothelium to non-muscle-invasive bladder cancer (NMIBC) or muscle-invasive bladder cancer (MIBC) is driven by complex molecular events, including chromosomal aberrations, somatic mutations, and epigenetic dysregulation. Advances in next-generation sequencing (NGS) and transcriptomic profiling have transformed the understanding of urothelial tumor biology and opened new perspectives for precision oncology. To provide an updated synthesis of molecular profiling in urothelial bladder cancer across disease stages and to discuss its diagnostic, prognostic, and therapeutic relevance. We conducted a targeted narrative review based on a structured PubMed search of studies published between January 2000 and February 2026 using the keywords "genomic," "epigenetic," "transcriptomic," and "urothelial bladder cancer." Eligible publications included original research articles, reviews, and meta-analyses in English. Evidence was synthesized across NMIBC, MIBC, and metastatic disease, focusing on molecular alterations and their clinical relevance. Both NMIBC and MIBC present frequent TERT promoter mutations. NMIBC is further characterized by frequent FGFR3 and PIK3CA mutations, loss of chromosome 9, and widespread chromatin-remodeling gene alterations. MIBC displays high genomic instability, with recurrent mutations in TP53, RB1, and chromatin modifiers, as well as frequent alterations in the RTK/RAS/PI3K pathway. Consensus transcriptomic classifications identify reproducible molecular subtypes (luminal, basal/squamous, stroma rich, and neuroendocrine like), each with distinct biological and clinical behaviors. In metastatic disease, NGS and whole-exome analyses reveal strong concordance with localized tumors, with frequent TP53, ARID1A, KMT2D, RB1, and FGFR3 alterations and APOBEC mutational signatures. Transcriptomic profiling shows subtype heterogeneity and therapy-induced remodeling. Clinically, only FGFR3 alterations currently guide therapy, with erdafitinib approved by the US Food and Drug Administration and the European Medicines Agency for FGFR3-altered metastatic disease. Beyond tumor testing, circulating tumor DNA assays show promise for molecular residual disease detection and adjuvant treatment stratification. Molecular profiling has deepened the understanding of bladder cancer biology and identified potential biomarkers for diagnosis, prognosis, and treatment. However, clinical implementation remains limited, and prospective biomarker-driven trials are needed to establish the role of genomic and transcriptomic alterations in therapeutic decision-making.

Immunotherapy-based combinations have improved overall survival (OS) in metastatic renal cell carcinoma (mRCC), but recent evidence suggests a therapeutic plateau, underscoring the need for more personalized strategies. Many patients start systemic therapy with the primary kidney tumor still in situ, and the role of cytoreductive nephrectomy (CN) in the immunotherapy era remains uncertain after CARMENA and SURTIME trials. In parallel, stereotactic body radiotherapy (SBRT) has emerged as a noninvasive option that achieves local control of primary RCC with limited toxicity. The ITALIC-RCC study evaluates whether local ablation of the primary tumor-by deferred CN or SBRT-improves outcomes in patients with mRCC who derive early benefit from anti-PD-1-based standard-of-care (SOC) therapy. ITALIC-RCC is a phase 4, randomized, multicenter trial. Patients with tumors &#x2264;4&#xa0;cm are randomized 1:1:1 to CN&#xa0;+&#xa0;SOC, radiotherapy (RT)&#xa0;+&#xa0;SOC, or SOC alone; those with tumors >4&#xa0;cm are randomized 1:1 to CN&#xa0;+&#xa0;SOC or SOC alone. The primary end point is OS comparing CN&#xa0;+&#xa0;SOC versus SOC alone from the time of randomization. Secondary end points include OS from systemic therapy initiation and progression-free survival (PFS) in the CN+SOC cohort versus the SOC-alone cohort, OS and PFS in the SBRT cohort, safety and complications of local treatments, and changes in quality of life. Exploratory end points include proteomic and tissue-based biomarkers associated with OS and PFS. The study plans to enroll 409 adults with predominantly clear-cell mRCC, Eastern Cooperative Oncology Group performance status 0-1, a primary tumor in situ, and no progression after 24-52&#xa0;wk of first-line anti-PD-1-based SOC (axitinib&#xa0;+&#xa0;pembrolizumab, cabozantinib&#xa0;+&#xa0;nivolumab, lenvatinib&#xa0;+&#xa0;pembrolizumab, or nivolumab after ipilimumab&#xa0;+&#xa0;nivolumab). Systemic therapy continues until progression by RECIST v1.1 or unacceptable toxicity. Imaging is performed every 12&#xa0;&#xb1;&#xa0;2&#xa0;wk. Safety is assessed by CTCAE v5.0 and Clavien-Dindo; quality of life by EQ-5D-5L and FKSI-19. Blood samples at randomization and 8&#xa0;&#xb1;&#xa0;2&#xa0;wk after intervention undergo proteomic profiling.Trial registrationClinicalTrials.gov identifier: NCT06903312.