Standard management for recurrent low-grade non-muscle-invasive bladder cancer (LG-NMIBC) often involves a substantial treatment burden, which is not justified by the relatively indolent course of the disease, prompting a need for de-intensification strategies. Active surveillance (AS) is an alternative approach aimed at reducing overtreatment in selected patients. However, the broader adoption of AS is hindered by a lack of standardized protocols for patient selection, monitoring and intervention. To address this gap, we conducted an international, two-round Delphi consensus among 51 bladder cancer experts to establish foundational statements for the use of AS. Consensus was achieved on 20 statements, providing clear recommendations for terminology; inclusion and exclusion criteria; follow-up monitoring; and exit criteria. This Delphi consensus provides the first expert-driven framework to standardize the clinical application of AS for LG-NMIBC. These statements could guide current clinical practice and unify the design of future trials.

BACKGROUND AND OBJECTIVE:To determine whether the existing European Organisation for Research and Treatment of Cancer (EORTC) QLQ-NMIBC24 and QLQ-BLM30 modules remain fit for purpose and to assess health-related quality of life (HRQoL) issues relevant for patients with metastatic bladder cancer (mBC). METHODS:Following the EORTC Quality of Life Group (QLG) guidelines, phase 1 included an expert meeting, five systematic reviews, and interviews with 14 healthcare professionals (HCPs) and 48 bladder cancer (BC) patients across six countries. HRQoL issues were identified through the literature and rated by HCPs and patients for relevance and importance. Decision rules guided selection for phase 2. In phase 2, selected issues were translated into items using the EORTC Item Library and expert consensus. KEY FINDINGS AND LIMITATIONS:A total of 443 articles and 62 interviews yielded 150 unique HRQoL issues; 40 issues and two branching questions were retained for the provisional module. Seventeen new items were added beyond the existing EORTC BC modules, while 11 existing items were excluded. Issues specific to mBC and newer treatments, such as immunotherapy, were identified. Limitations include potential selection bias due to purposive sampling and small sample sizes per treatment subgroup. CONCLUSIONS AND CLINICAL IMPLICATIONS:This phase 1-2 study supports the need to update the existing EORTC BC modules and incorporate additional items relevant to all disease stages, including mBC. A single, flexible module with branching logic may improve clinical applicability across patient subgroups. The provisional module will undergo international pretesting and psychometric evaluation in phase 3.

BACKGROUND AND OBJECTIVE: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. METHODS: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 FINDINGS AND LIMITATIONS: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-Guérin (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-NAÏVE 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. CONCLUSIONS AND CLINICAL IMPLICATIONS: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. PATIENT SUMMARY: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.

OBJECTIVES:Liquid-based biomarkers (LBBs), derived from urine and blood, are gaining attention in the management of upper tract urothelial carcinoma (UTUC) as potential tools to overcome limitations of current diagnostic and risk stratification pathways. This review evaluates emerging LBBs, focusing on diagnostic accuracy and their role in predicting high-grade and ≥pT2 disease. EVIDENCE ACQUISTION:A systematic search of MEDLINE, Embase, and the Cochrane CENTRAL (via Ovid) (January 2010-July 2024) identified studies reporting diagnostic performance of LBBs for UTUC, excluding urine cytology. Data on sensitivity, specificity, positive predictive value, negative predictive value, and area under the curve were extracted. A narrative synthesis was performed. EVIDENCE SYNTHESIS:Thirty-two studies met the inclusion criteria. Among bladder-derived urine biomarkers, RNA-based panels (an eight-gene panel: sensitivity 86-92%, specificity 87-93%) (low certainty) and DNA methylation panels-GDF15, TMEFF2, and VIM (sensitivity 91%, specificity 100%), Bladder Care Index (sensitivity 96%, specificity 88%), NRN1 (sensitivity 92-96%, specificity 92-95%) and ONECUT (sensitivity 89%, specificity 94%) and protein-based panels (BTA-STAT, BTA, and survivin) showed favourable diagnostic profiles (very low certainty). Upper-tract urine assays, EpiCheck (sensitivity 65-83%, specificity 79-83%), demonstrated modest accuracy (very low certainty for sensitivity; low certainty for specificity) with strong performance for high-grade disease. Among blood biomarkers, circulating tumour DNA (ctDNA) with plasma copy number burden >6.5 achieved high accuracy for predicting ≥pT2 and high-grade disease (sensitivity 71%, specificity 94%) (low certainty). CONCLUSIONS:RNA-based, DNA methylation-based, protein-based, and ctDNA-based assays showed promise for UTUC diagnosis and risk stratification. However, the current evidence is limited, with few validated studies. Large prospective cohorts and biomarker-driven interventional trials are needed before clinical integration.

Background and objective Distal ureterectomy (DU) is a kidney-sparing option for low-risk upper tract urothelial carcinoma (UTUC) and may be considered for selected high-risk cases. Long-term outcomes and recurrence predictors remain poorly defined. Our aim was to evaluate oncological outcomes of DU and identify preoperative predictors of disease recurrence, with a particular focus on ipsilateral upper tract recurrence (iUTR). Methods This retrospective multicentre study included 450 patients with nonmetastatic UTUC in the distal ureter treated with DU and bladder cuff excision between 2010 and 2023. The primary endpoint was iUTR-free survival (iUTRFS). Secondary endpoints were intravesical recurrence-free survival (IVRFS), recurrence-free survival (RFS), cancer-specific survival (CSS), overall survival (OS), and perioperative outcomes. Survival outcomes were visualised using Kaplan-Meier curves, and multivariable Cox regression analyses were performed. Key findings and limitations The 5-yr survival estimates were 82% for iUTRFS, 49% for IVRFS, 81% for RFS, 89% for CSS, and 72% for OS. IVRFS, iUTRFS, CSS, and OS did not significantly differ between the low-risk and high-risk groups. iUTR occurred in 16% of patients, with one in four of these cases arising after 5 yr. Salvage radical nephroureterectomy was performed in 10% of patients. Preoperative double-J stenting (hazard ratio [HR] 2.85, 95% confidence interval [CI] 1.11–7.30), tumour size (HR 1.04, 95% CI 1.01–1.07) and endoscopic bladder cuff management (HR 9.73, 95% CI 1.66–56.89) were independent predictors of iUTR. Perioperative complications were rare, with only 7% graded as high grade within 90 d. Limitations include the retrospective design, lack of centralised pathology review, and variability in surgical technique. Conclusions and clinical implications DU provides favourable perioperative and long-term oncological outcomes and may also be appropriate for selected high-risk cases. iUTR is not uncommon, and prolonged upper tract follow-up is essential. Avoidance of preoperative stenting and endoscopic bladder cuff management may reduce the risk of iUTR.

BACKGROUND AND OBJECTIVE:The current European Association of Urology (EAU) guidelines on non-muscle-invasive bladder cancer (NMIBC) categorize patients into four risk groups. In 2024, a specific follow-up schedule was introduced for intermediate-risk (IR) disease. However, recommendations are based on expert opinion and restricted to patients with IR-NMIBC who have primary low-grade or high-grade/grade 2 disease. Our aim was to identify a subgroup of patients with IR-NMIBC who may require more stringent follow-up. METHODS:We conducted a retrospective analysis of 2086 patients with IR-NMIBC classified according to the World Health Organization 1973 grading scheme. Multivariable Cox-regression models were fitted to identify predictors of recurrence, which were then used to dichotomize groups with low risk of recurrence (IR-Low) versus high risk of recurrence (IR-High). Kaplan-Meier curves were plotted to estimate recurrence-free survival (RFS) and progression-free survival (PFS). Smoothed hazard estimates of first recurrence were plotted by risk group. KEY FINDINGS AND LIMITATIONS:Multifocality and tumor size ≥3 cm were significantly associated with higher risk of first recurrence and were used to define the IR-High and IR-Low (unifocal, size <3 cm; n = 1087) groups. The 3-yr RFS rate was significantly worse for the IR-High group (51%, 95% confidence interval [CI] 48-54%) than for IR-Low (68%, 95% CI 65-71%). The risk of progression was low (5-yr PFS rate 96%) with no significant difference between the IR-High and IR-Low groups. CONCLUSIONS AND CLINICAL IMPLICATIONS:During IR-NMIBC follow-up for recurrence, tumor size and focality should be considered rather than grade. If the primary objective is to ensure prompt detection of recurrence, follow-up schedules should be tailored according to the risk of recurrence, with more stringent protocols for patients with IR-NMIBC at higher risk of recurrence.

BACKGROUND AND OBJECTIVE:We present a summary of the 2025 update for the European Association of Urology (EAU) guidelines for upper urinary tract urothelial carcinoma (UTUC). The aim is to provide practical recommendations on the clinical management of UTUC with a focus on diagnosis, treatment, and follow-up. METHODS:For the 2025 guidelines on UTUC, new and relevant evidence was identified, collated, and appraised via a structured assessment of the literature. Databases searched included Medline, EMBASE, and the Cochrane Libraries. 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 FINDINGS AND LIMITATIONS:Key recommendations emphasise the importance of thorough diagnosis, treatment, and follow-up for patients with UTUC. The guidelines stress the importance of appropriate treatment taking into account patient values and preferences. Key updates in the 2025 UTUC guidelines include: significant changes to the recommendations for UTUC diagnosis; complete revision of the sections addressing risk stratification, ureteroscopy, and the surgical approach for radical nephroureterectomy; addition of four new recommendations, two related to kidney-sparing management of localised low-risk UTUC and a further two related to management of high-risk nonmetastatic UTUC; a review and adaptation of recommendation for UTUC follow-up; and addition of a new section addressing quality indicators for UTUC management. CONCLUSIONS AND CLINICAL IMPLICATIONS:This overview of the 2025 EAU guidelines on UTUC offers valuable insights into risk factors, diagnosis, classification, treatment, and follow-up for UTUC. The guidelines contain information on the management of individual patients according to the current best evidence and are designed for effective integration in clinical practice.

BACKGROUND AND OBJECTIVE:Given the uncertainty regarding the role of radical nephroureterectomy (RNU) as part of a multimodal treatment strategy for upper tract urothelial carcinoma (UTUC) patients with cN+ disease, we aimed to perform a systematic review and meta-analysis of the corresponding literature. METHODS:Using the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines, we identified 17 observational comparative and noncomparative studies, published between January 2000 and September 2024, evaluating UTUC patients with cTanyN+M0 disease (P) who received RNU as part of a multimodal treatment strategy (I), as compared with any treatment strategy if applicable (C), to assess oncological or postoperative outcomes (O). Meta-analyses were further performed, as appropriate. KEY FINDINGS AND LIMITATIONS:Overall, 15 studies evaluated the effectiveness of adding chemotherapy to RNU in the perioperative setting without specifying the exact timing of delivery (n = 1), in the induction setting (n = 14), or in the adjuvant setting (n = 5), while two studies evaluated the effectiveness of adding RNU to chemotherapy. Meta-analyses showed that the use of induction chemotherapy plus RNU versus RNU alone was associated with greater odds of pathological downstaging (risk ratio [RR] = 3.06; 95% confidence interval [CI] = [2.48-3.77]; p < 0.001; I2 = 0%; p = 0.44) and pathological complete nodal response (RR = 2.80; 95% CI = [2.03-3.86]; p < 0.001; I2 = 0%; p = 0.47) as well as prolonged overall survival (HR = 0.52; 95% CI = [0.42-0.64]; p < 0.001; I2 = 14%; p = 0.33) without any significant impact on the risk of overall (RR = 1.14; 95% CI = [0.79-1.64]; p = 0.48; I2 = 0%; p = 0.76) and major (RR = 0.48; 95% CI = [0.18-1.24]; p = 0.13; I2 = 0%; p = 0.87) postoperative complications. In addition, the use of induction chemotherapy plus RNU versus RNU plus adjuvant chemotherapy (HR = 0.58; 95% CI = [0.38-0.89]; p = 0.01) or chemotherapy alone (HR = 0.49; 95% CI = [0.32-0.76]; p = 0.001; I2 = 46%; p = 0.17) was associated with prolonged overall survival. Limitations include the observational design of all included studies. CONCLUSIONS AND CLINICAL IMPLICATIONS:The use of RNU could provide the greatest oncological benefits without any significant harm in selected UTUC patients with fit general condition and resectable cN+ disease responding to induction chemotherapy. PATIENT SUMMARY:In this report, we looked at the outcomes of radical surgery in combination with systemic chemotherapy for upper tract urothelial carcinoma with clinical evidence of dissemination to the surrounding lymph nodes. We observed that the use of radical surgery was associated with the greatest oncological benefits without any increased risk of postoperative complications in patients with fit general condition and resectable disease responding to induction chemotherapy. We conclude that the use of induction chemotherapy plus radical surgery could be the best multimodal treatment strategy for these patients.

Background and objective Bacillus Calmette-Guérin (BCG) reduces disease recurrence and progression in intermediate- and high-risk non–muscle-invasive bladder cancer (NMIBC). BCG-associated adverse events during instillations are common, leading to treatment cessation. Prophylactic use of quinolones in conjunction with BCG instillations is one approach for reducing BCG-associated adverse events. Our aim was to delineate the clinical impact of quinolone prophylaxis (QP) in patients receiving adjuvant BCG instillations for NMIBC. Methods In October 2024, a systematic search of MEDLINE, Embase, and the Cochrane Central Register of controlled trials was performed. Prospective and retrospective studies reporting comparative outcomes for patients with and without QP during BCG instillations were included. Outcomes were reported in a binary fashion. Random-effects meta-analysis using the weighted mean difference was conducted. Primary outcomes for pooled analyses included BCG-associated toxicities, the completion rate for BCG induction, the likelihood of antituberculosis treatment, and disease recurrence and progression at 12 mo. Key findings and limitations The systematic review included five studies. Four randomised controlled trials were included in the meta-analysis, and one nonrandomised study was also included in the narrative review. The studies involved 445 patients, of whom 194 received QP + BCG and 251 received BCG alone. QP use was associated with lower incidence of class ≥2 (40.8% vs 54.7%; relative risk [RR] 0.79, 95% confidence interval [CI] 0.67–0.94; p = 0.006), and class ≥3 BCG-associated toxicities (25.3% vs 36.4%; RR 0.70, 95% CI 0.50–0.98; p = 0.04) and a higher completion rate for BCG induction (83.0% vs 70.6%; RR 1.16, 95% CI 1.01–1.34; p = 0.04). The 12-mo recurrence rates (14.7% vs 19.4%; RR 0.76, 95% CI 0.46–1.27; p = 0.3) and progression rates (4.5% vs 6.4%; RR 0.86, 95% CI 0.09–8.25; p = 0.9) did not significantly differ for QP + BCG versus BCG alone. Conclusions and clinical implications The use of QP with adjuvant BCG for NMIBC mitigated debilitating BCG-associated toxicities and improved the completion rate for BCG induction therapy.

Background and objective: This publication represents a summary of the updated 2024 European Association of Urology (EAU) guidelines for non-muscle-invasive bladder cancer (NMIBC), TaT1, and carcinoma in situ. 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. Methods: For the 2024 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 Libraries. 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 findings and limitations: 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. Conclusions and clinical implications: This overview of the 2024 EAU guidelines offers valuable insights into risk factors, diagnosis, classification, prognostic factors, treatment, and follow-up of NMIBC. These guidelines are designed for effective integration into clinical practice. (c) 2024 European Association of Urology. Published by Elsevier B.V. All rights are reserved, including those for text and data mining, AI training, and similar technologies.