BACKGROUND:Although intermediate clinical endpoints (ICEs) may expedite completion of randomized controlled trials (RCTs) evaluating perioperative systemic treatments for localized muscle-invasive bladder cancer (MIBC), no validated surrogate for overall survival (OS) has been established. We aimed to assess the surrogacy of pathologic complete response (pCR), pathologic objective response (pOR), and disease-free survival (DFS) for OS. PATIENTS AND METHODS:We analyzed 4,828 patients with MIBC (cT2-T4N0M0) who underwent radical cystectomy (RC) with or without neoadjuvant chemotherapy (NAC) across 29 European centers (2001-2024). The inverse probability of treatment weighting (IPTW) approach was used to adjust for confounding between NAC and RC-only groups. Surrogacy was evaluated using: (1) adapted Prentice criteria to test whether each ICE remained a significant predictor of OS while the treatment effect disappeared in IPTW-adjusted multivariable Cox models; (2) the proportion of treatment effect explained (PTE); and (3) an emulated 2-stage meta-analytic framework to estimate the pseudo-trial-level R2 between treatment effects on each ICE and OS across 1,000 replicates of 5 random clusters. The surrogate threshold effect (STE) was calculated for ICEs demonstrating strong surrogacy (R2≥0.7). RESULTS:Overall, 1,288 (26.7%) patients received NAC followed by RC and 3,540 (73.3%) underwent RC alone. In IPTW-adjusted Cox regression analyses including NAC and each ICE separately, pCR (hazard ratio [HR], 0.32; 95% CI, 0.24-0.41; P<.001), pOR (HR, 0.26; 95% CI, 0.21-0.31; P<.001), and DFS (HR, 5.17; 95% CI, 4.56-5.86; P<.001) were independent predictors of OS. The PTE was 0.42 (95% CI, 0.22-0.54), 0.48 (95% CI, 0.24-0.58), and 0.84 (95% CI, 0.66-0.96) for pCR, pOR, and DFS, respectively. At the pseudo-trial level, the R2 was 0.22 (95% CI, 0.20-0.25), 0.33 (95% CI, 0.31-0.36), and 0.83 (95% CI, 0.81-0.84) for the correlation between treatment effects on pCR, pOR, and DFS and OS, respectively. The STE was 0.82 (95% CI, 0.81-0.84) for DFS. CONCLUSIONS:We observed uncertainty regarding the surrogacy of pCR and pOR in patients undergoing RC with or without NAC for localized MIBC. Only DFS consistently mediated the treatment effect on OS, supporting its use as a surrogate for RCT dimensioning when a recurrence or death risk reduction of ≥18% is expected.

To evaluate the oncological outcomes of second-look transurethral resection of bladder tumor (TURBT) in patients with a high grade (HG) Ta non-muscle invasive bladder cancer (NMIBC). We conducted a real-life multicenter study including all consecutive patients with HG Ta NMIBC, with or without second TURBT. Oncological outcomes included disease recurrence and progression. Multivariable Cox regression analyses were used to identify the independent predictors of bladder recurrence and progression. Of the 447 patients with HG Ta NMIBC, 240 (53.7

INTRODUCTION:Intravesical instillations of mitomycin C, epirubicin, and BCG are considered as the standard of care for most patients with non-muscle invasive bladder cancer (NMIBC). These guidelines aim to optimize intravesical instillations in order to improve their efficacy and decrease morbidity. MATERIAL:An analysis of good practice, available regulations, and published guidelines was conducted through an online literature search in French and English using Medline® and Embase®, up to December 2025. The following keywords were used: "BCG"; "Mitomycin C"; "Epirubicin"; "Bladder"; "Complication"; "Toxicity"; "Adverse reaction"; "Prevention"; "Treatment". RESULTS:Information should be given to the patient by the attending physician before the first intravesical instillation. A medical examination to detect specific contraindications is also mandatory to select appropriate therapy. Intravesical instillations should be delivered in health-care centers where urological endoscopic procedures are performed routinely. Screening for or treating asymptomatic bacteriuria prior to intravesical chemotherapy or BCG instillation is not recommended. In the presence of a clinically apparent urinary tract infection, instillations should be postponed. Intravesical instillation can only be delivered after a bladder catheter has been inserted without any injury to the lower urinary tract. The pharmaceutical agent should be retained in the bladder for 2h. Finally, voiding within 6h after intravesical instillation should be done in the seated position and the patient should drink at least 2L of water per day for 2 days. CONCLUSION:The delivery of intravesical instillations of mitomycin C, epirubicin and BCG should follow a standardized procedure for better efficacy and lower morbidity.

INTRODUCTION:Intravesical instillations of BCG are recommended for the treatment of high-risk non-muscle invasive bladder cancer. However, their prolonged use remains limited by potentially serious adverse events (AEs) or complications. The aim of this article is to provide updated recommendations for the diagnosis and management of AEs or complications of intravesical BCG instillations. MATERIALS:A review of the literature was performed using Medline (http://www.ncbi.nlm.nih.gov) and Embase (http://www.embase.com), and the following MeSH keywords or a combination of keywords: "Bladder"; "BCG"; "Complication"; "Toxicity"; "Adverse events"; "Prevention"; "Treatment". RESULTS:AEs or complications of BCG included genitourinary and systemic symptoms. The most common complications (cystitis, moderate fever) should be treated symptomatically and may require BCG adjustment to allow patients to have the most complete BCG course possible. Serious complications are rare but must be identified promptly because of their life-threatening nature. Their management is based on a combination of anti-tubercular treatment, anti-inflammatory drugs, and permanent discontinuation of BCG. CONCLUSION:The management of AEs during BCG therapy requires early identification, rational and effective treatment if necessary, and discussions about the continuation of BCG therapy in each situation.

The purpose of this study was to evaluate the oncological and perioperative outcomes of robot-assisted bladder cuff excision (RA-BCE) versus open bladder cuff excision (O-BCE) after radical nephroureterectomy (RNU) for patients with upper tract urothelial carcinoma (UTUC). We conducted a multicenter study including all consecutive patients who underwent RA-BCE or O-BCE in eight French academic institutions from 2014 to 2023. Kaplan–Meier curves were used to illustrate survival outcomes, while uni- and multivariable Cox regression analyses were conducted to identify independent predictors of survival by calculating hazard (HRs) ratios with their corresponding 95

BACKGROUND:Radical cystectomy with pelvic lymph node dissection (PLND) remains the standard treatment for muscle-invasive bladder cancer (MIBC). Neoadjuvant chemotherapy (NAC) improves survival, and recent immunochemotherapy trials have reported complete pathological responses in up to 60% of patients, increasing interest in bladder-sparing strategies. However, the ability to accurately identify patients without residual pelvic lymph node metastases after NAC remains limited. OBJECTIVE:To evaluate the association between pathological response in the bladder and pelvic lymph node status after NAC in patients with MIBC undergoing radical cystectomy (RC) and PLND. DESIGN, SETTING, AND PARTICIPANTS:This retrospective, multi-institutional cohort study included 751 patients with MIBC treated with NAC followed by RC and PLND between 2000 and 2021 across 26 institutions. INTERVENTION:Neoadjuvant chemotherapy followed by RC and PLND. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS:The primary outcome was residual lymph node involvement (ypN+). Multivariable logistic regression was used to identify factors associated with ypN+. RESULTS AND LIMITATIONS:Overall, 175 patients (23%) achieved a complete pathological response in the bladder (ypT0), 102 (14%) were downstaged to non-muscle-invasive disease (ypTa/ypTis/ypT1), and 185 (25%) had residual lymph node involvement. On multivariable analysis, cN+ disease before NAC was associated with higher odds of ypN+ (OR 1.97, 95% CI 1.32-2.94), whereas ypT0 (OR 0.11, 95% CI 0.05-0.21) and ypTa/ypTis/ypT1 (OR 0.24, 95% CI 0.12-0.47) were associated with lower odds of ypN+. Notably, 5% of ypT0 and 10% of downstaged patients harboured residual lymph node metastases. Limitations include potential selection bias and centre-level variability in surgical and pathological assessment, which may affect the generalizability of the findings. CONCLUSIONS:Current clinical and radiological variables cannot reliably exclude residual pelvic lymph node disease, even in patients achieving ypT0-1. Novel imaging techniques and liquid biomarkers require validation before bladder-sparing approaches can be safely expanded.

IntroductionUpper urinary tract tumors (UUTT) are imprecisely diagnosed. Recent data have shown the benefit of adding systemic treatments to advanced local stage tumors (≥T2). MRI has provided useful information for evaluating the local T stage of urinary bladder tumors, which may be used for UUTT. The objective of this study was to review the literature on the diagnostic and staging capabilities of MRI for UUTT. Additionally, the methods for performing MRI on the UUT were evaluated.MethodsThis review was conducted according to the PRISMA using MEDLINE and EMBASE. All original articles published between January 2000 and February 2024 that investigated the diagnostic and staging performance of MRI in patients with suspected UUTT were included in this study.ResultsFifteen studies were included, comprising 999 patients, of whom 593 had UUTT. A wide heterogeneity in the sequences was observed. While standard acquisition (T1 weighted + T2 weighted) showed insufficient diagnostic performance, dynamic contrast imaging (DCE) and diffusion weighted imaging (DWI) presented strong diagnostic scores for pooled sensitivity (92.5% and 93.2%), specificity (76.7% and 84.2%), and accuracy of diagnosis (91.1% and 90.1%), respectively. DWI and apparent diffusion coefficient (ADC) seem to be informative for staging and prognostic evaluation.Discussion and conclusionMRI has strong potential to enhance UUTT diagnosis and staging. Despite heterogeneous data and limited evidence, the findings of this study suggest that further large multicentric studies should be conducted to better evaluate the diagnostic performance of MRI in UUT, with a predefined standard acquisition compared to the pathology report of radical nephroureterectomy or long-term follow-up by medical imaging. We hope to establish an Upper Urinary Tract Imaging-Reporting and Data System (MRI UUTI-RADS) score for predicting muscle invasion and tumor stage.Patient summaryWe performed a systematic evaluation and summary of all studies published on the diagnostic and staging capabilities of MRI for upper urinary tract tumors. This review showed a lack of evidence data but a strong potential for MRI. A predefined MRI protocol was proposed for future studies.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/, identifier CRD42022319265.

CONTEXT: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. OBJECTIVE:To provide an updated synthesis of molecular profiling in urothelial bladder cancer across disease stages and to discuss its diagnostic, prognostic, and therapeutic relevance. EVIDENCE ACQUISITION: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. EVIDENCE SYNTHESIS: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. CONCLUSIONS: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.

One of the most striking features of the adipose depot surrounding the prostate [periprostatic adipose tissue (PPAT)] is that its accumulation is independent of body mass index. Its volume varies considerably between individuals, with some patients exhibiting abundant PPATs, which have been correlated to the occurrence of aggressive prostate cancer (PCa). However, abundant PPAT is not well defined at the biological level. We used a new statistical approach to define abundant PPAT by normalizing PPAT volume to prostate volume in a cohort of 351 patients using a linear regression model. Applying this definition, we confirmed the link between abundant PPAT and PCa aggressiveness, thereby validating our approach. At the biological level, we showed that abundant PPAT exhibited extensive extracellular matrix remodeling, notably of the collagen network, decreasing the mechanical constraints in hypertrophic adipocytes, leading to inflammation-free expansion. Degradation of the most abundant collagen in adipose tissue (AT), collagen VI, was associated with increased production of endotrophin, a signaling peptide derived from AT that was also elevated in the urine of patients with abundant PPAT confirming the clinical relevance of our results. These results highlight a unique mechanism of expansion of an adipose depot and open new mechanistic avenues to explain its role in prostate-related disorders. © 2026 The Pathological Society of Great Britain and Ireland.

Tertiary lymphoid structures (TLS) have emerged as critical immune niches within the tumor microenvironment across various cancers. However, their structural organization and functional roles in non-muscle-invasive bladder cancer (NMIBC) remain poorly characterized. In this study, we comprehensively characterized TLS in NMIBC using en bloc resected primary diagnostic specimens, which enabled high-resolution spatial mapping and quantitative histological assessment across a large cohort of primary tumors (97 patients). Compared with TLS in inflammation-driven cystitis, tumor-associated TLS showed heterogeneous spatial organization, altered immune composition, and disrupted follicular dendritic cell (FDC) networks with reduced high endothelial venules density. TLS density increased with NMIBC grade and stage and correlated with higher recurrence risk and shorter progression-free survival in multivariable analysis. Paired analysis of primary and recurrent tumors showed a reduction in FDC density and a shift from M1 to M2 differentiation in tumor recurrences, suggesting the development of an immunosuppressive microenvironment. Single-cell RNA sequencing of TLS from NMIBC and cystitis samples revealed impaired germinal center activity in tumor-associated TLS, with asynchronous B-cell maturation and reduced B-cell interactions with both T follicular helper cells and FDC. Tumor-associated TLS also showed increased myeloid infiltration and altered dendritic-cell function, including reduced MHC class II antigen presentation and downregulation of co-stimulatory (CD86-CD28) and migration-related (CD99) pathways compared to TLS from cystitis samples. Overall, we found that NMIBC-associated TLS are structurally and functionally impaired, which may limit effective local immune responses and suggests they may be relevant as biomarkers and targets for immunomodulatory therapy in bladder cancer.

Non-muscle-invasive bladder cancer (NMIBC) is a heterogeneous disease, with Ta tumors accounting for about 70

BACKGROUND AND OBJECTIVE:Muscle-invasive bladder cancer (MIBC) may present de novo (primary MIBC [pMIBC]) or progress from non-muscle-invasive disease (secondary MIBC [sMIBC]). While sMIBC has been associated with adverse outcomes after radical cystectomy, its prognostic impact in patients undergoing trimodal therapy (TMT) is unclear. We aimed to compare the outcomes between pMIBC and sMIBC in a multicenter cohort treated with bladder-preserving TMT. METHODS:We conducted a retrospective study including patients with MIBC treated with curative-intent TMT. Eligible patients had stage ≥T2 disease and completed TMT without discontinuation. Patients were classified as those having pMIBC (≥T2 at diagnosis) or sMIBC (progression after prior non-muscle-invasive bladder cancer [NMIBC]). The primary endpoint was recurrence-free survival; the secondary endpoints were metastasis-free survival, cancer-specific survival (CSS), overall survival, and treatment-related toxicity. Survival was assessed using Kaplan-Meier methods and multivariable Cox regression. KEY FINDINGS AND LIMITATIONS:Among 294 patients (234 with pMIBC and 60 with sMIBC), the median age was 77 yr. The median follow-up was 34 mo for pMIBC and 24 mo for sMIBC. The 3-yr CSS rate was 78% for pMIBC and 79% for sMIBC. After adjustment for clinical covariates, sMIBC was not associated with an increased risk of recurrence (hazard ratio [HR] 1.35, 95% confidence interval [CI] 0.85-2.13) and cancer-specific death (HR 0.88, 95% CI 0.44-1.76). Toxicities were mostly of grade 1-2; grade ≥3 events were rare. Limitations include the retrospective design, a smaller sMIBC subgroup, and a relatively short follow-up. CONCLUSIONS AND CLINICAL IMPLICATIONS:Outcomes after TMT were broadly similar between pMIBC and sMIBC, although overall survival was lower in patients with secondary disease. A prior NMIBC history should therefore not preclude consideration of bladder-preserving therapy in appropriately selected patients.

PURPOSE:To evaluate the prognostic value of tumor size in patients with low-risk upper tract urothelial carcinoma (UTUC) undergoing radical nephroureterectomy (RNU). METHODS: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 ≥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. RESULTS: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 ≥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 ≥2cm was a significant predictor of disease recurrence with HR=7.18; 95%CI=[2.94-17.5]; P<0.001. CONCLUSIONS:Tumor size ≥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. LEVEL OF EVIDENCE: 4:

Squamous cell carcinoma (SCC) of the bladder is a rare subtype accounting for 2-5% of bladder cancers in Western countries. Its epidemiology, biological drivers, and clinical behavior differ substantially from urothelial carcinoma (UC), yet most management strategies remain extrapolated from UC due to the absence of dedicated evidence. Robust data are limited, and therapeutic decision-making is challenged by the rarity of this aggressive variant. Bladder SCC is strongly associated with chronic inflammatory conditions, including schistosomiasis, long-term catheterization, and recurrent urinary infections. Most patients present with muscle-invasive disease, characterized by marked local aggressiveness and a lower incidence of early nodal or distant metastases compared with UC. Molecular profiling indicates a predominant basal/squamous phenotype with frequent EGFR pathway activation and TP53/RB1 alterations, highlighting potential therapeutic vulnerabilities. However, the efficacy of perioperative chemotherapy, immunotherapy, or antibody-drug conjugates remains uncertain, as SCC patients are consistently underrepresented in clinical trials and outcomes are rarely reported separately. Emerging targeted strategies, such as Nectin-4 and Trop-2-directed agents, show promise but require prospective, SCC-specific evaluation. Bladder SCC remains an orphan malignancy with significant unmet clinical needs. Dedicated multicenter efforts are crucial to refine diagnostic pathways, integrate molecular characterization, and develop tailored therapeutic approaches. The French AVENTUR Group aims to address these gaps by coordinating national collaboration across institutions and promoting prospective clinical and translational research to improve outcomes in this rare and aggressive bladder cancer subtype.

Introduction Treatment patterns for patients with bacillus Calmette-Guérin (BCG)–unresponsive high-risk non–muscle-invasive bladder cancer (NMIBC) who are ineligible for or decline radical cystectomy (RC) are inconsistently reported. We retrospectively described demographic, clinical, and treatment characteristics for these patients and assessed their clinical outcomes. Patients and Methods Medical charts of patients with BCG-unresponsive high-risk NMIBC (carcinoma in situ [cohort A] or T1/high-grade Ta [cohort B]) who were ineligible for or declined RC documented between January 1, 2011, and December 31, 2018, at 15 academic centers were reviewed. Primary objectives were to characterize demographic, clinical, and nonsurgical treatment characteristics. Secondary objectives included assessing real-world progression-free survival (rw-PFS) from muscle-invasive/metastatic disease, rw-PFS from worsening grade or stage, real-world complete response rate (rw-CRR) in cohort A, real-world event-free survival (rw-EFS) from high-risk NMIBC in cohort B, and overall survival. Results The study included 129 patients (cohort A, n = 57; cohort B, n = 72). Median age was 72.0 years (interquartile range, 64.0-80.0). Most patients were male (72.1%) and current/former smokers (69.8%). Median follow-up was 32.1 months (interquartile range, 20.7-47.6). BCG rechallenge with or without interferon-α (63.6%) was the most commonly utilized first nonsurgical therapy, followed by intravesical mitomycin C with or without electromotive drug administration or thermochemotherapy (15.5%), and intravesical valrubicin (10.9%); among those who received BCG rechallenge alone, 54.8% later received a non-BCG therapy in ≥2 subsequent treatments. 36-month rate for rw-PFS from muscle-invasive/metastatic disease was 73.5%, 66.8% for rw-PFS from worsening grade/stage, and 82.5% for overall survival. In cohort A, 6-month rw-CRR was 22.2%. In cohort B, 36-month rw-EFS rate from high-risk NMIBC was 50.2%. Conclusion After BCG-unresponsive disease, most patients with high-risk NMIBC received BCG rechallenge with or without other therapies, and >25% experienced disease progression within the first 3 years. Effective bladder-sparing options for BCG-unresponsive NMIBC are needed. Clinical trial registration N/A MicroAbstract We reviewed medical records from 15 international hospitals to understand treatment patterns and outcomes in patients with high-risk non–muscle-invasive bladder cancer (NMIBC) unresponsive to bacillus Calmette-Guérin who were ineligible for or declined radical cystectomy. We found that bladder-sparing options were historically limited and more effective bladder-sparing options are needed for this patient population.

Intermediate-risk prostate cancer (PCa) is a heterogeneous subgroup for which the optimal treatment strategy remains a subject of debate. Of all the emerging options, high-intensity focused ultrasound (HIFU) therapy aims to treat the tumor while preserving healthy prostate structures. However, the post-treatment surveillance protocol remains poorly defined, particularly due to the limitations of PSA testing and conventional imaging. This narrative review evaluates the contribution of PSMA-PET metabolic imaging in post-HIFU follow-up compared to standard techniques (PSA, multiparametric MRI). A narrative review of the literature was conducted in the Medline, PubMed, and Cochrane (2008–2025) databases. Studies evaluating post-HIFU follow-up by PSA, mpMRI, and/or PSMA-PET were included. Data were analyzed descriptively and critically by two independent reviewers. Eight studies were included out of the 1245 identified articles. Although mpMRI is currently standard, its sensitivity and specificity in the treated area is limited due to post-HIFU anatomical changes. The recently developed PI-FAB score improves the standardization of interpretation but remains operator-dependent. On the other hand, PSMA-PET offers excellent specificity (100

BACKGROUND AND OBJECTIVE:It remains currently unknown whether the effectiveness of neoadjuvant chemotherapy (NAC) before radical cystectomy (RC) for muscle-invasive bladder cancer (MIBC) is the same in patients with or without prior non-muscle invasive bladder cancer (NMIBC). This study aims to perform a real-world analysis of the predictive value of prior NMIBC for the effectiveness of NAC in patients undergoing RC for MIBC. METHODS:We included 2378 patients from the BLADRAC cohort who received RC with (n = 870; 37%) or without (n = 1508; 63%) NAC for primary (n = 1825; 77%) or secondary (n = 553; 23%) MIBC at 15 French centers from 2001 to 2023. Multivariable logistic regression models were fitted to identify the predictors of NAC delivery as well as those of pathological complete (pCR = [y]pT0N0) and pathological objective (pOR ≤[y]pT1N0) responses, while we assessed the predictors of recurrence-free (RFS), cancer-specific (CSS), and overall (OS) survival using multivariable Cox regression models. The heterogeneity of treatment effect of NAC according to the occurrence of prior NMIBC was determined further by testing the interaction terms between the occurrence of prior NMIBC and the effect of NAC within the models evaluating pathological and survival outcomes. KEY FINDINGS AND LIMITATIONS:Patients with secondary MIBC were significantly less likely to receive NAC (odds ratio [OR] = 0.63; 95% confidence interval [CI] = [0.5-0.79]; p < 0.001) than those with primary MIBC. The use of NAC was an independent predictor of better pCR (OR = 6.02; 95% CI = [4.63-7.83]; p < 0.001), pOR (OR = 5.08; 95% CI = [4.09-6.3]; p < 0.001), RFS (HR = 0.61; 95% CI = [0.53-0.71]; p < 0.001), CSS (HR = 0.57; 95% CI = [0.47-0.69]; p < 0.001), and OS (HR = 0.61; 95% CI = [0.51-0.72]; p < 0.001), while the occurrence of prior NMIBC was not significantly associated with any of these endpoints (all p > 0.05). There was no significant interaction between the occurrence of prior NMIBC and the impact of NAC on pCR, pOR, RFS, CSS, and OS (all pinteraction > 0.05). The study is limited by its retrospective design. CONCLUSIONS AND CLINICAL IMPLICATIONS:Our real-world data suggest that the occurrence of prior NMIBC could limit the access to NAC, while not predicting its effectiveness in patients treated with RC for localized MIBC.