BACKGROUND:Sequential intravesical gemcitabine and docetaxel (Gem/Doce) are increasingly used for nonmuscle-invasive bladder cancer (NMIBC), especially in the setting of Bacillus Calmette-Guérin (BCG) shortage or failure. However, the contribution of docetaxel to gemcitabine remains unquantified. We compared the effectiveness of gemcitabine alone vs. Gem/Doce in high-risk NMIBC. METHODS:We conducted a retrospective study of 296 patients treated with gemcitabine (n = 173) or Gem/Doce (n = 123) at 3 Mayo Clinic sites between 2018 and 2023. The primary outcome was high-grade recurrence-free survival (HGRFS). Secondary outcomes included recurrence-free, progression-free, cystectomy-free, cancer-specific, and overall survival and adverse events. Analyses included Kaplan-Meier and Cox regression with 2-stage residual inclusion to adjust for confounding. RESULTS:Median HGRFS was similar between groups (gemcitabine: 22.6 months; Gem/Doce: 19.5 months [P = 0.25]). Among patients with BCG-unresponsive carcinoma in situ (n = 49), median HGRFS was comparable (gemcitabine: 12.2 months; Gem/Doce: 7.6 months [P = 0.12]). No significant differences were observed for secondary outcomes. In the 2-stage residual inclusion analysis, Gem/Doce was not associated with improved HGRFS (hazard ratio [HR], 1.09; 95% CI, 0.65-1.82; P = 0.80), including among patients with BCG-unresponsive disease (HR, 2.24; 95% CI, 0.96-5.24 [P = .06]). Low-grade adverse events were common (gemcitabine: 63%; Gem/Doce: 55% [P = 0.19]), but grade ≥3 adverse events were rare (2.3% vs. 2.4%). Limitations included imbalances in maintenance utilization (gemcitabine: 19%; Gem/Doce: 40%), baseline characteristics, gemcitabine dosing, and follow-up duration between cohorts. CONCLUSIONS:In this multicenter study, Gem/Doce was not associated with improved outcomes compared with gemcitabine alone. Prospective trials are needed to quantify the specific contribution of docetaxel in NMIBC.

BACKGROUND:There are few bladder-sparing treatment options for high-risk, BCG-unresponsive, non-muscle-invasive bladder cancer that are effective and have a manageable adverse event profile. Cretostimogene grenadenorepvec (hereafter, cretostimogene) is an oncolytic immunotherapy with dual mechanisms of action-it replicates in and lyses cancer cells with retinoblastoma-E2F pathway alterations and amplifies the immune response. We evaluated the response and safety/tolerability of cretostimogene in patients with high-risk, BCG-unresponsive, non-muscle-invasive bladder cancer. METHODS:BOND-003 Cohort C is a single-arm, international, phase 3 study done in 41 centres (community practices and academic centres) located in North America, Asia, and Australia. Sites were selected through a study team-led qualification process that evaluated feasibility, protocol alignment, operational capabilities, and regulatory readiness, as applicable. We enrolled patients aged at least 18 years with Eastern Cooperative Oncology Group performance status of 0-2 and pathologically confirmed, high-risk, BCG-unresponsive, non-muscle-invasive bladder cancer with carcinoma in situ, with or without resected high-grade Ta or T1 disease. Patients received intravesical cretostimogene (1 × 1012 viral particles per 0·8 mL per week) as 6-week induction followed by maintenance; re-induction was permitted for persistent disease at 3 months. The primary endpoint was centrally confirmed complete response at any time in patients who received at least one dose of cretostimogene and completed the 3-month assessment; safety was assessed in those who received at least one dose of cretostimogene. This trial is registered with ClinicalTrials.gov (NCT04452591) and is ongoing. FINDINGS:Between Oct 9, 2020, and Aug 3, 2023, 165 patients were assessed for eligibility; 115 patients were enrolled in the study and 112 received cretostimogene. 83 (74%) were male and 29 (26%) were female; median age was 74·0 years (IQR 68·5-79·5). As of June 23, 2025, after a median follow-up of 25·8 months (IQR 22·1-33·1), complete response at any time was observed in 83 (75% [95% CI 66·3-83·2]) of 110 patients. 71 (63%) of 112 patients had at least one treatment-related adverse event, the most common being bladder spasm in 28 (25%) patients, pollakiuria in 25 (22%) patients, and micturition urgency in 23 (21%) patients; there were no grade 3 or 4 treatment-related adverse events and no treatment-related discontinuations or deaths. Two (2%) patients had serious treatment-related adverse events (one non-infective cystitis and one urinary bladder haemorrhage, both grade 2). INTERPRETATION:Cretostimogene showed clinically meaningful anti-tumour response, with an adverse event profile characterised predominantly by low-grade, transient events. Cretostimogene shows promise as an innovative bladder-sparing treatment for high-risk, BCG-unresponsive, non-muscle-invasive bladder cancer with carcinoma in situ. FUNDING:CG Oncology.

Purpose:Compared with white-light cystoscopy (WLC), blue-light cystoscopy (BLC) enhances detection of non-muscle-invasive bladder cancer (NMIBC), especially carcinoma in situ (CIS). However, its effects on health care resource utilization and cost burden have not been fully elucidated. This study assessed the economic implications of BLC vs WLC. Materials and Methods:We conducted a retrospective cohort analysis with claims data from the Optum Research Database between June 2011 and May 2023. Patients who underwent BLC or WLC were identified, and white-light patients were matched 6:1 to blue-light patients by index year and time between bladder cancer diagnosis and cystoscopy. Inverse probability of treatment weighting was used to adjust for baseline differences. Health care resource utilization and total and bladder cancer-specific costs were calculated on a per-patient-per-month basis. Results:The final cohort included 794 blue-light and 4764 white-light patients. Before weighting, claims coded for CIS were more frequent in blue-light patients (19.6% vs 8.8%; P < .001). Blue-light patients underwent more upper-tract imaging (71.8% vs 57.8%; P < .001), BCG (24.2% vs 15.8%; P < .001), and biomarker testing (65.0% vs 34.9%; P < .001). After weighting, blue-light patients had a higher mean number of bladder cancer-related ambulatory visits per month (1.3 vs 1.0; P = .004). However, neither all-cause health care resource utilization (3.47 vs 3.21; P = .11) nor total cost ($2987.93 vs $2886.16, per patient per month, P = .65) differed significantly between cohorts. Conclusions:BLC is associated with greater health care resource utilization for NMIBC without significantly elevating health care costs, suggesting that enhanced diagnostic strategies can be implemented without added financial burden in real-world practice.

PURPOSE:To compare patient-reported and clinical outcomes between radical cystectomy (RC) and bladder-sparing therapy (BST) in patients with recurrent high-grade non-muscle-invasive bladder cancer (NMIBC). PATIENTS AND METHODS:This pragmatic, prospective observational cohort study was designed with patients, who selected and prioritized outcomes. Eligible adults were candidates for both RC or BST, had previous induction Bacillus Calmette-Guérin (BCG), and received their last treatment within 12 months. The primary outcome was the EORTC-QLQ-C30 physical function scale at 12 months. Secondary outcomes included other EORTC-QLQ-C30 scales, depression, anxiety, bladder cancer-specific quality of life (QOL), financial burden, and cancer-specific outcomes. Targeted maximum likelihood estimation (TMLE) was used to calculate average treatment effect (ATE) estimates between arms. Inverse probability weighted risk ratios (wRR) were calculated using quasi-Poisson regression. RESULTS:Of 570 participants (mean age 71.4 years; 21% female), 371 selected BST and 199 selected RC. Physical function was significantly worse in the RC arm at 3 months; by 9 months, there was no difference between arms, and at 12 months, physical function did not differ (ATE, 0.9; 95% CI, -0.6 to 2.4; P = .22). RC was associated with better emotional function, generic health-related QOL, and financial burden, and lower depression and anxiety, while BST was associated with better bowel and sexual health. Cancer-specific survival was 99% for BST versus 96% for RC (wRR, 0.99; 95% CI, 0.97 to 1.01). RC was associated with a higher risk of adverse events and serious adverse events, including a 90-day mortality rate of 2.5%. CONCLUSION:Most patient-prioritized outcomes were similar or better among participants who chose RC compared with BST. These findings support the continued role of RC in managing recurrent high-grade NMIBC.

BACKGROUND:Nadofaragene firadenovec-vncg received US Food and Drug Administration approval for bacille Calmette-Guérin (BCG)-unresponsive non-muscle-invasive bladder cancer (NMIBC) based on prospective efficacy and safety results. However, postmarketing data are lacking. This study evaluates outcomes in a real-world setting. METHODS:We analyzed data for patients treated at Mayo Clinic from November 2023 through December 2024. Outcomes included complete response (CR) rate, duration of response, adverse events, and high-grade recurrence-free (HGRFS), cystectomy-free, and overall survival. RESULTS:Forty-six patients were treated with nadofaragene firadenovec; 3 with pending posttreatment cystoscopy were excluded. Of 24 evaluable patients with carcinoma in situ with/without papillary disease, 79% had a CR at 3 months. The median response duration was not reached; 68% (13/19) of responders still had CRs with median follow-up of 9.3 months. Of 19 patients with papillary-only disease (median follow-up of 7.6 months), HGRFS at 3, 6, and 12 months was 68%, 53%, and 26%, respectively. With median follow-up of 13.9 months, cystectomy-free and overall survival were 93% and 95%, respectively. Progression occurred in 5 patients. The most common adverse events were grade 1-2 bladder spasms (61%) and failure to fully retain the instillation (33%). Four patients had grade 3 events; there were no grade 4 or 5 events. Limitations include the small sample size and limited follow-up. CONCLUSIONS:Real-world data confirm the efficacy and safety of nadofaragene firadenovec, clarifying its role in the management of BCG-unresponsive NMIBC.

716 Background: Nadofaragene firadenovec is an FDA-approved gene therapy for Bacillus Calmette-Guérin (BCG) unresponsive non-muscle invasive bladder cancer (NMIBC) with promising clinical trial results. However, real-world post-marketing efficacy or safety data remain lacking. We evaluated complete response rates and safety in a multisite experience. Methods: Per IRB protocol, we analyzed patients treated with nadofaragene firadenovec for BCG-unresponsive NMIBC across three Mayo Clinic sites. Outcomes included complete response (CR), high-grade recurrence-free survival (HGRFS), cystectomy-free survival (CFS), overall survival (OS), and adverse events (AEs). CR and HGRFS were reported for patients with carcinoma in situ (CIS) and patients with Ta/T1 without CIS respectively. Failure to retain was defined as any medication loss, including leakage around the catheter or early voiding. Results: Between November 2023 and October 2024, 45 patients were treated with nadofaragene firadenovec for BCG-unresponsive NMIBC. Fifteen patients with follow-up less than 6 months and one patient with extensive metastatic disease identified one week after first instillation were excluded from efficacy analysis. Our efficacy-evaluable population of 29 patients with median follow-up of 8.2 months is summarized in the Table. CR/HGRFS at 3 and 6 months was 72% and 62% respectively. CFS was 94% and OS was 100% at 6 months. Three patients experienced disease progression during follow-up: one to T1, another to T2, and a third with metastases to the abdomen and lungs. A separate patient developed a metachronous upper tract urothelial carcinoma (pT2) without bladder recurrence. Bladder spasms (62%) and failure to retain (31%) were the most common AEs. Most AEs were low-grade, although four (9%) patients had grade 3 events (fatigue, fever, and dizziness). No grade 4-5 AEs were reported. Conclusions: Early real-world data demonstrates encouraging clinical complete response rates in patients with BCG-unresponsive NMIBC and a favorable safety profile. Further investigation with larger cohorts and longer follow-up is warranted. Evaluable patients (N=29) CIS cohort (N=15) Ta/T1 only cohort (N=14) Prior pembrolizumab (N=9) Prior intravesical chemotherapy (N=16) Age, years 72 (67-77) 74 (69-77) 71 (67-77) 69 (67-78) 73 (67-81) Elixhauser Index 5 (4-6) 5 (4-7) 5 (4-6) 5 (3-5) 5 (3-6) Prior BCG instillations 12 (10-14) 12 (12-15) 11 (8-13) 12 (12-12) 12 (11-13) Prior intravesical chemotherapy among recipients 6 (6-11) 6 (6-10) 6 (6-11) 10 (7-12) 6 (6-11) Prior pembrolizumab doses among recipients 7 (4-8) 8 (7-8) 4 (4-4) 7 (4-8) 8 (5-8) Follow-up, months 8.2 (6.9-9.5) 7.6 (6.9-9.5) 8.5 (6.9-9.4) 9.1 (8.0-10.1) 8.6 (6.7-9.9) 3-month CR/HGRFS 72% [53-87] 73% [45-92] 71% [42-92] 67% [30-93] 56% [30-80] 6-month CR/HGRFS 62% [42-79] 67% [38-88] 57% [29-82] 44% [14-79] 44% [20-70] Data are median (IQR) or % [95% CI].

INTRODUCTION:We aimed to characterize patient portal messaging use after urologic surgery to identify administrative burden and evaluate postoperative clinical associations. METHODS:Epic was queried for all urologic surgeries performed at the Mayo Clinic enterprise between 2019 and 2022. Data from the highest volume procedures were extracted including patient-generated portal messages to their provider and emergency department (ED) visits within 6 months of surgery. Factors associated with portal users and message volume, as well as the impact of portal use on risk of subsequent ED visit, were evaluated. RESULTS:We analyzed data from 23,621 urologic procedures, which generated 102,726 patient portal messages within 6 months of surgery. We found that 55% of our cohort sent at least 1 message. Stratifying by subspecialty, endourologic surgeries generated the fewest number of messages per surgery (3.83; SD, 8.76), whereas female pelvic medicine and reconstructive surgeries yielded the most (6.05; SD, 10.92). Younger age, female sex, and White race were associated with increased portal utilization. Multivariable time-to-event analysis revealed a 33% reduction in the risk of ED presentation within 90 days after surgery for patients using the patient portal compared with those who did not. CONCLUSIONS:While only half of patients sent portal messages after surgery, active users showed a 33% reduction in ED visits, suggesting its potential to reduce health care utilization. Encouraging broader portal adoption can improve outcomes. However, the message burden for urologists necessitates solutions. Resource allocation should prioritize strategies to help urologists manage messages while preserving the established clinical benefits.

Introduction The American Urological Association (AUA)/Society of Urology Oncology (SUO) guidelines recommend a repeat transurethral resection of bladder tumor (TURBT) for high-risk, non-invasive (HR Ta) nonmuscle invasive bladder cancer (NMIBC) patients. The evidence base for this recommendation is weak (grade C) and fraught with methodological shortcomings, such as the lack of adjuvant intravesical Bacillus Calmette Gurein (BCG) and single-center study designs. We sought to evaluate the effect of repeat TURBT on recurrence-free survival at a population level in HR Ta NMIBC patients who completed BCG induction therapy. Methods High-grade Ta NMIBC patients who underwent TURBT for a ≥5cm tumor were identified within the SEER-Medicare database from 2000 to 2015. All patients completed induction BCG and were stratified into two groups: repeat TURBT within eight weeks of initial TURBT and a group without repeat TURBT (control group). The primary endpoint was the 3-year high-risk recurrence rate. Results A cohort of 591 patients was identified, with 88 (14.9%) undergoing a repeat TURBT within eight weeks of initial TURBT and 503 (85.1%) without a repeat TURBT. Patient demographic and clinical characteristics were similar overall. No significant difference in the 3-year recurrence rate was noted (repeat TURBT group 20.5% vs. control group 14.7%, p=0.17). After adjusting for demographic and clinical characteristics, no association between repeat TURBT and 3-year high-risk recurrence was observed (HR (95% CI): 1.34 (0.79, 2.25); p=0.28) (Figure 1). A Kaplan Meier with Logrank test (KM) showed no significant difference in 3-year recurrence-free survival between the repeat TURBT and control groups (p = 0.19) (Figure 2). Conclusions In patients with large volume HG Ta NMIBC with completion of induction BCG therapy repeat TURBT was not associated with decreased high-risk recurrence-free survival. While repeat TURBT does likely identify residual disease in a subsection of this population, the implementation of a high-quality initial resection in conjunction with the treatment benefit of BCG therapy may nullify the therapeutic benefit of repeat TURBT. These data underscore the need for additional studies evaluating the utility of repeat TURBT in HR Ta NMIBC, ideally in a cooperative group setting.

OBJECTIVES:To compare survival and oncological outcomes of cisplatin-ineligible patients (Cis-I) and cisplatin-eligible (Cis-E) patients with muscle-invasive bladder cancer (MIBC) undergoing immediate radical cystectomy (IRC), as IRC is currently considered the standard-of-care for Cis-I patients with MIBC. PATIENTS AND METHODS:Data from patients with clinical (c)T2-4cN0-1M0 MIBC undergoing IRC, between 2006 and 2021, were retrospectively analysed from four tertiary care centres in the United States. Overall, recurrence-free and event-free survival were described using the Kaplan-Meier method and tested using the log-rank test. For context, we compared survival outcomes against those in Cis-E patients with MIBC undergoing IRC from the Southwest Oncology Group (SWOG)-8710 trial. RESULTS:Overall, 379 Cis-I and 125 Cis-E patients with cT2-4cN0-1M0 MIBC who underwent IRC were included. Cis-I patients included 44.8% cT3/4 vs 60% cT3/4 in the Cis-E group. Overall, 83.3% of Cis-I and 79.2% of Cis-E patients died during follow-up. The median event-free and overall survival were 12.1 and 14.5 months for the Cis-I group and 28.8 and 60.1 months for the Cis-E group (P < 0.001). [Correction added on 10 October 2025, after first online publication: The preceding sentence has been revised in this version.] Limitations include retrospective comparison of contemporary multi-institutional data with that of a randomised control trial. CONCLUSIONS:The Cis-I patients with MIBC undergoing IRC fared poorly, with a median overall survival of 14.5 (95% confidence interval 11.1-17.9) months, mostly due to non-cancer-related deaths. These results provide a benchmark for clinical trials exploring novel agents or alternative chemotherapy regimens in Cis-I patients with MIBC.