Low-risk Non-muscle Invasive Bladder Cancer Research Articles

Prospective Assessment of VI-RADS with Muscle Invasion in Urinary Bladder Cancer and Its Implication on Re-Resection/Restaging TURBT Patients.

Bladder cancer (BCa) diagnosis relies on distinguishing muscle-invasive bladder cancer (MIBC) from non-muscle-invasive bladder cancer (NMIBC) forms. Transurethral resection of the bladder tumor (TURBT) is a standard procedure for initial staging and treatment. The Vesical Imaging-Reporting and Data System (VI-RADS) enhances diagnostic accuracy for muscle invasiveness through advanced imaging techniques, potentially reducing reliance on repeat TURBT and improving patient management. We aimed to evaluate the role of VI-RADS in predicting muscle invasiveness in BCa and its potential to predict adverse pathology in high-risk NMIBC to avoid unnecessary repeat TURBT procedures. In this prospective study, we included 62 patients over the age of 18years who underwent TURBT. In a secondary phase, patients selected for restaging TURBT (re-TURBT) were included, but those with T2 tumors or low-risk NMIBC were excluded. Multiparametric magnetic resonance imaging (MRI) examinations were scored by a radiologist using the VI-RADS 5 method, while a pathologist analyzed TURBT and re-TURBT samples for accurate staging. Statistical analysis evaluated the role of VI-RADS in BCa staging. The VI-RADS score was the only predictive factor for muscle invasion in multivariate analysis. Setting the VI-RADS score at >3 resulted in the highest sensitivity, specificity, and diagnostic accuracy, with values of 67.0%, 89.0%, and 78%, respectively. The receiver operating characteristic area under the curve score for VI-RADS for muscle invasion was 85% for stage Ta, 61% for stage T1, and 88% for stage T2, which shows the utility of VI-RADS in the predictiveness of MIBC/NMIBC. VI-RADS is effective in stratifying BCa patients by predicting muscle invasiveness and identifying NMIBC cases that may not need repeat TURBT.

Tumor microenvironment-modulating oncolytic adenovirus combined with GSK-3β inhibitor enhances antitumor immune response against bladder cancer.

Bladder cancer is a common type of cancer around the world, and the majority of patients are diagnosed with non-muscle-invasive bladder cancer (NMIBC). Although low-risk NMIBC has a good prognosis, the disease recurrence rate and development of treatment-refractory disease remain high in intermediate- to high-risk NMIBC patients. To address these challenges for the treatment of NMIBC, a novel combination therapy composed of an oncolytic adenovirus (oAd) co-expressing interleukin (IL)-12, granulocyte-macrophage colony-stimulating factor (GM-CSF), and relaxin (RLX; HY-oAd) and a clinical-stage glycogen synthase kinase (GSK)-3β inhibitor (9-ING-41; elraglusib) was investigated in the present report. Our findings demonstrate that HY-oAd and 9-ING-41 combination therapy (HY-oAd+9-ING-41) exerted superior inhibition of tumor growth compared with respective monotherapy in a syngeneic NMIBC tumor model. HY-oAd+9-ING-41 induced high-level tumor extracellular matrix (ECM) degradation and a more potent antitumor immune response than the respective monotherapy. In detail, HY-oAd+9-ING-41 induced superior accumulation of intratumoral T cells, prevention of immune cell exhaustion, and induction of tumor-specific adaptive immune response compared to either monotherapy. Collectively, these results demonstrate that the combination of HY-oAd and 9-ING-41 may be a promising approach to elicit a potent antitumor immune response against bladder cancer.

BladderGATE: Atezolizumab + intravesical BCG (bacillus Calmette-Guerin) upfront combination in patients with high risk non-muscle invasive bladder cancer (NMIBC)—Phase I-II ONCOSUR study.

595 Background: Intravesical Bacillus Calmette-Guerin (BCG) induction + BCG maintenance after transurethral resection is the current standard of care for patients (pts) with high-risk non-muscle invasive bladder cancer (NMIBC). Recurrence rate at 2 years and 5 years are around 30-40% and 70-80% respectively. Atezolizumab is a IgG1 monoclonal antibody targeting PD-L1 and is associated with long-term durable remissions in pts with metastatic urothelial cancer (MS. van der Heijden . Eur Urol 2021) and for pts with unresponsive NMIBC (PC. Black . Eur Urol 2023) with excellent results. Atezolizumab in combination with standard BCG could provide synergistic benefit for pts with NMIBC. BladderGATE (NCT04134000) is a phase Ib-II study which evaluates the safety and efficacy of upfront atezolizumab + intravesical BCG in pts with high-risk NMIBC. Methods: Pt had confirmed histopathology of high-risk NMIBC, BCG naïve or stopped >2 years ago, WHO PS 0-2 and adequate hematologic and organ function. Dose-escalation design to identify DLT and MTD (9 pts) and to evaluate safety and efficacy in an expansion cohort (30 pts) were programed. Pt received six weekly induction instillations, and maintenance instillations at 3, 6 and 12 months + intravenously atezolizumab 1200 mg every 3 weeks, up to 1 year. Urine/blood and tissue samples were collected for translational and biomarker correlative study. Primary objective is disease free survival. Secondary objectives include safety profile and quality of life. Results: Finally 36 pt were included, median age 70 years, 86% men, 61% of pt were former smokers, 22% smokers and 17% had never smoked, and tumor size was ≥3 cm in 44% of pt. With a 22 months median follow-up, 56% of pt had completed BCG treatment and 89% had received adequate BCG treatment (5 induction plus at least 2 maintenance instillations). Thirteen pts discontinued atezolizumab due to immune-related AEs (7 pts) (g2 dermatitis, g3 hepatitis, encephalitis, pneumonitis, myocarditis, adrenal insufficiency and psoriasis), due to early-relapse disease (3 pts) and progressive-disease (3 pts). All irAEs were solved and no toxic death were reported. Of the 36 pts analyzed, 6 pts showed local recurrence (17%), 5 pts with high-risk NMIBC (14%) and 1 pt with low-risk NMIBC, 1 pt with UTUC, and 3 pts with local muscle invasive bladder cancer progressive-disease (8 %). Preliminary 2-year disease free survival is 72.8% (95% CI: 56.1% - 89.5%). Conclusions: The combination strategy of atezolizumab + intravesical BCG upfront in high-risk NMIBC pts appears feasible and safe. A 14% of 2-years local recurrence-rate and 8% of local progressive-disease are promising results, pending to randomized Ph3 ALBAN study data (GETUG). Supported by Roche-Spain. Clinical trial information: NCT03425201 .

Long-term Recurrence Rates of Low-risk Non–muscle-invasive Bladder Cancer—How Long Is Cystoscopic Surveillance Necessary?

BackgroundWhile low-risk non–muscle-invasive bladder cancer (LR-NMIBC) has a low propensity to progress, the risk of recurrence remains high (50% within 4 yr). Guidelines recommend cystoscopic surveillance after resection, but the necessary duration of follow-up is debated. ObjectiveTo determine the risk of recurrence beyond 5 yr after diagnosis in patients with LR-NMIBC, and to identify risk factors of recurrence. Design, setting, and participantsIn this multicenter retrospective observational study, patients who received their first transurethral bladder tumor resection before 2016 for LR-NMIBC were included. Low risk was defined as a primary, solitary, low grade, Ta bladder tumor measuring <3 cm. Outcome measurements and statistical analysisThe primary endpoint was determination of the recurrence rates at 1, 2, and 5 yr. The secondary endpoints included overall recurrence-free survival (RFS) and high-risk RFS. A univariate analysis and multivariable logistic regression were performed to assess the risk factors for recurrence over the study period. Results and limitationsThe median age of the 577 patients was 70.9 yr, and 126 (21.8%) patients were female. The median follow-up was 69.6 (interquartile range: 58.4) mo, and recurrence was observed in 236 (40.9%) patients. The 1-, 2-, and 5-yr RFS rates were 81.6% (95% confidence interval 78.4–84.9), 72.4% (68.7–76.3), and 59.2% (55–63.8), respectively. Recurrence after 5 yr was observed in 13.1% (28/213). High-risk recurrence, defined as the first recurrence of a high-grade and/or ≥T1 tumor, occurred in 6.2% (36/579) overall and 2.8% (6/213) after 5 yr. The lack of a single postoperative dose of chemotherapy and tumor size >2 cm were prognostic factors of recurrence. ConclusionsThe risk of recurrence in patients with LR-NMIBC decreases progressively after the 1st year and remains low beyond 5 yr. Discontinuation of endoscopic surveillance after 5 yr in patients with LR-NMIBC can be discussed. Treatment with postoperative chemotherapy and tumor size <2 cm may be relevant variables to identify patients who will benefit from cystoscopic follow-up as short as 12 mo. Patient summaryIn this study, we observed that 13% of patients who did not have a recurrence during the first 5 yr following the diagnosis of low-risk non–muscle-invasive bladder cancer will recur after this time point. Discontinuation of cystoscopic surveillance can be discussed after 5 yr in these patients.

Intermediate and high-risk non-muscle-invasive bladder cancer: an overview of epidemiology, burden, and unmet needs.

Bladder cancer ranks among the most common cancers globally. At diagnosis, 75% of patients have non-muscle-invasive bladder cancer (NMIBC). Patients with low-risk NMIBC have a good prognosis, but recurrence and progression rates remain high in intermediate- and high-risk NMIBC, despite the decades-long availability of effective treatments for NMIBC such as intravesical Bacillus Calmette-Guérin (BCG). The present review provides an overview of NMIBC, including its burden and treatment options, and then reviews aspects that counteract the successful treatment of NMIBC, referred to as unmet treatment needs. The scale and reasons for each unmet need are described based on a comprehensive review of the literature, including insufficient adherence to treatment guidelines by physicians because of insufficient knowledge, training, or access to certain therapy options. Low rates of lifestyle changes and treatment completion by patients, due to BCG shortages or toxicities and adverse events as well as their impact on social activities, represent additional areas of potential improvement. Highly heterogeneous evidence for the effectiveness and safety of some treatments limits the comparability of results across studies. As a result, efforts are underway to standardize treatment schedules for BCG, but intravesical chemotherapy schedules remain unstandardized. In addition, risk-scoring models often perform unsatisfactorily due to significant differences between derivation and real-world cohorts. Reporting in clinical trials suffers from a lack of consistent outcomes reporting in bladder cancer clinical trials, paired with an under-representation of racial and ethnic minorities in many trials.

PD13-04 DEVELOPMENT OF A NOVEL GENE EXPRESSION SCORING SYSTEM FOR RECURRENCE IN NON-MUSCLE-INVASIVE BLADDER CANCER AFTER TRANSURETHRAL RESECTION OF BLADDER TUMOR

You have accessJournal of UrologyCME1 Apr 2023PD13-04 DEVELOPMENT OF A NOVEL GENE EXPRESSION SCORING SYSTEM FOR RECURRENCE IN NON-MUSCLE-INVASIVE BLADDER CANCER AFTER TRANSURETHRAL RESECTION OF BLADDER TUMOR Emina Kayama, Motohide Uemura, Yusuke Kirihana, Akifumi Onagi, Seiji Hoshi, Tomoyuki Koguchi, Tomohiko Yanagida, Fusao Murakami, and Yoshiyuki Kojima Emina KayamaEmina Kayama More articles by this author , Motohide UemuraMotohide Uemura More articles by this author , Yusuke KirihanaYusuke Kirihana More articles by this author , Akifumi OnagiAkifumi Onagi More articles by this author , Seiji HoshiSeiji Hoshi More articles by this author , Tomoyuki KoguchiTomoyuki Koguchi More articles by this author , Tomohiko YanagidaTomohiko Yanagida More articles by this author , Fusao MurakamiFusao Murakami More articles by this author , and Yoshiyuki KojimaYoshiyuki Kojima More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003260.04AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Non-muscle-invasive bladder cancer (NMIBC) frequently recurs after transurethral resection of bladder tumor (TURBT). However, clinical prognostic factors do not always accurately predict tumor recurrence. Therefore, we developed a new gene expression scoring system that is practical for distinguishing between high- and low-risk NMIBC that recur after TURBT. METHODS: We included 89 patients (median age 75) diagnosed with NMIBC after initial TURBT without prior or concurrent upper tract urothelial carcinoma at our institution between 2008 and 2019. This study obtained the approval of the institutional ethics board and the patient's consent. Variations in the expression signature of 14,400 genes within each patient were measured by our microarray analysis which has no mRNA amplification bias, not requiring validation by quantitative reverse transcriptase PCR. A hierarchical cluster analysis was performed to identify a set of genes that discriminates between high- and low-risk NMIBC. RESULTS: Eleven genes were extracted that predict tumor recurrence after TURBT. The cumulative equivalent of the 11 genes (microarray score) was obtained from each sample, and the optimal cutoff score was calculated to be 1.29 (area under the curve 0.83). A Kaplan-Meier curve showed the 5-year recurrence-free survival (RFS) rate was 38.2% in the “high microarray score group” (microarray score ≥1.29, n=39), which was significantly lower than in the “low microarray score group” (82.6%, p=0.002, Figure 1). The 5-year RFS rate in patients with single, Ta low grade tumor <3 cm in diameter without CIS (n=15) was 90.0%, which was higher than in the rest (55.2%); however, no significant difference was observed (p=0.063). Multivariate Cox regression analysis showed that a microarray score ≥1.29 was an independent factor for disease recurrence (hazard ratio 3.89, p=0.005), but clinical factors were not. CONCLUSIONS: Our novel gene expression scoring system proved to be more useful in predicting recurrence in patients with NMIBC after TURBT than clinical prognostic factors. This scoring system may enable individualized strategic management of high-risk NMIBC patients. Source of Funding: None © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e406 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Emina Kayama More articles by this author Motohide Uemura More articles by this author Yusuke Kirihana More articles by this author Akifumi Onagi More articles by this author Seiji Hoshi More articles by this author Tomoyuki Koguchi More articles by this author Tomohiko Yanagida More articles by this author Fusao Murakami More articles by this author Yoshiyuki Kojima More articles by this author Expand All Advertisement PDF downloadLoading ...

Urine Cytology Rarely Escalates Clinical Management in the Surveillance of Non-muscle-Invasive Bladder Cancer.

The use of urine cytology in the surveillance of non-muscle invasive bladder cancer (NMIBC) is widely variable in clinical practice. We studied the impact of surveillance urine cytology on clinical decision making during NMIBC surveillance. A retrospective chart review was conducted on patients surveilled for clinical NMIBC from 2013 to 2020 with at least one follow-up cytology result after diagnosis. Patients were classified into risk categories according to American Urological Association (AUA) NMIBC guidelines. Data were obtained regarding tumor recurrence pathology and the frequency and findings of surveillance cystoscopies and urine cytologies. Positive (suspicious, malignant) and negative (atypical or negative for malignant cells) cytology results were correlated with cystoscopy and pathology findings when obtained within 3 months of the cytology specimen to determine if cytology impacted plan of care. Two hundred fourteen patients with NMIBC were followed for a median of 34 months, with 1045 urine cytologies collectively obtained over the surveillance period. There were no positive urine cytologies among patients with low-risk NMIBC; therefore, cytology did not change management in this cohort. The potential for cytology to escalate management for patients of any risk group (ie, positive cytology in the absence of positive cystoscopy or pathology findings) occurred in 30 (2.9%) cases. However, clinical decision making was only altered in 4 cases (0.4% of all cytologies). Less than 1% of urine cytology specimens collected during NMIBC surveillance impacted clinical management, none of whom had low-risk disease. The use of urine cytology for surveillance of low-risk NMIBC should continue to be strongly discouraged, as it did not change management in any such cases.

Adherence to guidelines in the follow-up of non-muscle-invasive bladder cancer among urology trainers and trainees in Jordan: a cross-sectional study.

An electronic questionnaire containing, in addition to demographic data, four questions regarding the follow-up of NMIBC was sent by e-mail to 115 urologists (53 residents and 62 specialists) selected randomly by stratified random sampling from different clinical institutions, 105 of them were returned complete. In all, 105 out of 115 (91%) questionnaires were returned complete. All of the candidates are male. For low-risk NMIBC follow-up, 46 of the specialists (79%) and 35 of the trainees (74%) decided to do a follow-up cystoscopy at 3 months after diagnosis, followed by a check cystoscopy 9 months later than yearly, while for high-risk patients, all of the specialists and 45 of the trainees (96%) decide to do a check cystoscopy every 3 months in the first 2 years after diagnosis. For upper tract follow-up in high-risk NMIBC, all of the urologists in the survey (specialists and trainees) routinely perform upper tract imaging in the form of a computed tomography scan with contrast in the first year after diagnosis. On the other hand, in the follow-up of the upper urinary tract in low-risk NMIBC, 16 of the trainees (34%) and 19 of the specialists (33%) still perform a yearly scan. Because of the high recurrence rate for NMIBC, this raises the importance of adherence to guidelines in the follow-up for these patients and, at the same time to avoid overdoing unnecessary cystoscopies or upper tract scans.

A phase 1, open-label trial to evaluate feasibility and safety of intramural injection of belzupacap sarotalocan (AU-011) in non-muscle–invasive bladder cancer (NMIBC).

TPS596 Background: A high unmet medical need exists for new therapies in NMIBC to reduce common risks of recurrence, progression and, ultimately, cystectomy. Belzupacap sarotalocan, a novel investigational virus-like drug conjugate (VDC), has a dual mechanism of action designed to provide 1) selective binding to malignant cells, causing acute necrosis upon light activation, and 2) long-term anti-tumor immunity as demonstrated in pre-clinical models. This Phase 1 trial is designed to evaluate the feasibility and safety of intramural injection with or without intratumoral injection of belzupacap sarotalocan for treatment of NMIBC. The hypothesis is that after near infrared light activation, targeted distribution of belzupacap sarotalocan at high concentrations at the tumor base could necrose the tumor where it is most likely to be invasive. In turn, the tumor targeted pro-immunogenic cell death could potentially lead to an anti-tumor immune response preventing the risk for recurrence, progression and metastasis. Methods: This is an actively enrolling “window of opportunity” trial (NCT05483868) in low, medium or high risk NMIBC subjects scheduled to undergo TURBT or cystectomy per standard of care. A pre-treatment biopsy will be performed in up to 23 adult subjects enrolled in 4 cohorts, who will be given belzupacap sarotalocan +/- laser as shown in the table. The primary endpoint is incidence and severity of treatment-related adverse events, serious adverse events regardless of attribution, and incidence of dose-limiting toxicities. Each cohort will have a safety review for the injection procedure and laser (as needed), after 3 subjects have been treated and followed for 28 days. Secondary endpoints are based on histopathology and include assessment of local biodistribution of belzupacap sarotalocan measured via immunohistochemical staining, tumor necrosis, and evidence of an immune response via comparison of pre-treatment biopsy to TURBT/cystectomy samples after treatment. Statistical analysis plan includes descriptive statistics for the above endpoints. Clinical trial information: NCT05483868 . [Table: see text]

Bladder EpiCheck urine test in the follow-up of NMIBC: a cost analysis.

In the Netherlands yearly more than 5000 patients are diagnosed with non-muscle invasive bladder cancer (NMIBC). With a specificity of 88.0% and a negative predictive value (NPV) for high grade NMIBC of 99.3%, the Bladder EpiCheck (BE) urine test may be used in NMIBC to reduce the burden of follow-up cystoscopies. In this study a cost analysis of the BE follow-up strategy in the Dutch healthcare system was performed. In half of the follow-up appointments, BE was used as a rule-in for cystoscopy. In addition, the possible delay in recurrence detection was estimated. A cost calculation tool was developed using Microsoft Excel. The BE strategy results in an estimated cost reduction of 8%, 4% and 9% in low, intermediate and high risk patients, respectively. In the Netherlands this may result in a cost reduction of approximately 1.6 million euro per year. The estimated delay in the detection of recurrent disease would be 3.9, 1.7 and 1.3months in low, intermediate and high risk NMIBC patients respectively. To conclude, the BE can be used to reduce the costs of NMIBC follow-up, with a small delay in diagnosis of recurrent disease.

Immediate post-operative intravesical instillation of a single dose chemotherapy is not superior to continuous saline irrigation

Introduction and objectivesTo evaluate whether there is any difference between immediate postoperative instillation of intravesical chemotherapy (IPOIC) and continuous saline bladder irrigation (CSBI) in terms of bladder cancer (BC) recurrence in patients with primary low- or intermediate-risk non-muscle-invasive BC (NMIBC). Materials and methodsMedical records of 1482 patients who underwent transurethral resection of bladder tumor between March 1994 and August 2020 were reviewed retrospectively. Patients were divided into two groups according to IPOIC and/or CSBI administration status [Group-1 = CSBI alone; Group-2 = CSBI following IPOIC]. Low- and intermediate-risk NMIBC patients were also divided into subgroups according to IPOIC and/or CSBI administration status. ResultsA total of 594 patients with primary NMIBC were included. Of the patients, 86 (14.5%) were female and 508 (85.5%) were male with a median age of 69 (60–78) years. The frequency of patients in Group-1 and Group-2 were 361 (60.8%) and 233 (39.2%), respectively. Recurrent disease was observed in 213 (35.9%) patients. There was no difference between the groups when they were compared for recurrent disease frequency, median time to first recurrence and frequency of recurrence within first 12 months (P = .064, P = .671, and P = .145, respectively). Disease recurrence rates in low-risk NMIBC patients was lower when they were treated with “CSBI following IPOIC” when compared to “CSBI alone” (P = .042). However, no difference was observed in low-risk NMIBC subgroups when they were compared for pathological features of recurrent tumors such as number, size, grade, stage, and presence of carcinoma in situ (P > .05, for each). Conclusions“CSBI following IPOIC” combination was not superior to “CSBI alone” for preventing adverse pathological outcomes in recurrent low- and intermediate-risk NMIBC.

The natural history of low-risk non-muscle-invasive bladder cancer: a collaborative multi-centre study.

International guidelines vary in terms of their definition and recommendation for management of low-risk non-muscle-invasive bladder cancer (LRNMIBC). The ideal management for this large subset of bladder cancer patient remains unclear. To evaluate long-term outcomes of patients with LRNMIBC. As a secondary objective, to assess for intergroup heterogeneity in disease-specific outcomes between G1 and G2LG diseases. A multi-centre, retrospective study of patients who met the 2015 NICE definition of LRNMIBC. Timeline of diagnosis ranged from 01/01/2012 to 30/06/2016. A total 390 patients had available follow-up data (G1: 142, G2LG: 249). Over a median follow-up time of 36months (IQR 25-50), 29.2% of the patients developed a recurrence. G2LG patients were statistically more likely to develop a recurrence (G1: 26.8%, G2LG: 33.7%, p < 0.05). 51.8% of recurrences occurred after 1year of surveillance. Progression to high-grade disease occurred in 1.8% (n = 7, G1: 3, G2LG: 4) and a further 1.0% (n = 4, G1:3, G2LG: 1) of patients developed muscle-invasive bladder cancer (MIBC). The majority of recurrences occurred after 1year of surveillance. The risk of disease progression was low; however, this was observed in a cohort of patients with regular cystoscopic follow-up. The risk may be higher if patients were pre-maturely discharged. If a 5-year surveillance programme were to be followed, 96.5% of recurrences would be captured. Lastly, there appears to be intergroup heterogeneity within LRNMIBC with G2LG patients having a statistically higher risk of recurrence compared to G1.

La dosis única de instilación intravesical postoperatoria inmediata de quimioterapia no es superior al lavado continuo con suero

Introduction and objectivesTo evaluate whether there is any difference between immediate postoperative instillation of intravesical chemotherapy (IPOIC) and continuous saline bladder irrigation(CSBI) in terms of bladder cancer(BC) recurrence in patients with primary low- or intermediate-risk non-muscle-invasive BC (NMIBC). Materials and methodsMedical records of 1482 patients who underwent transurethral resection of bladder tumor between March 1994 and August 2020 were reviewed retrospectively. Patients were divided into two groups according to IPOIC and/or CSBI administration status (Group 1: CSBI alone; Group 2: CSBI following IPOIC). Low- and intermediate-risk NMIBC patients were also divided into subgroups according to IPOIC and/or CSBI administration status. ResultsA total of 594 patients with primary NMIBC were included. Of the patients, 86 (14.5%) were female and 508 (85.5%) were male with a median age of 69 (60-78) years. The frequency of patients in group 1 and group 2 were 361 (60.8%) and 233 (39.2%), respectively. Recurrent disease was observed in 213 (35.9%) patients. There was no difference between the groups when they were compared for recurrent disease frequency, median time to first recurrence and frequency of recurrence within first 12 months (P=.064, P=.671, and P=.145, respectively). Disease recurrence rates in low-risk NMIBC patients was lower when they were treated with “CSBI following IPOIC” when compared to “CSBI alone” (P=.042). However, no difference was observed in low-risk NMIBC subgroups when they were compared for pathological features of recurrent tumors such as number, size, grade, stage, and presence of carcinoma in situ (P>.05, for each). Conclusions“CSBI following IPOIC” combination was not superior to “CSBI alone” for preventing adverse pathological outcomes in recurrent low- and intermediate-risk NMIBC.

Impact of Urinary pH on the Efficacy of a Postoperative Single Instillation of Mitomycin-C.

To assess the effect of the urinary pH value on the efficacy of a postoperative single instillation of mitomycin-C. A descriptive study. Department of Urology, Ankara Numune Training and Research Hospital, Ankara, Turkey from 2011 to 2016. Patients newly diagnosed with low-risk non-muscle invasive bladder cancer and given a postoperative single instillation of mitomycin-C were retrospectively reviewed. The demographic data and pre-instillation urinary pH values of the patients were recorded. All patients included in the study (n=117) were followed up for five years. The primary outcome was the time to the first recurrence. The patients were divided into two groups: Group 1 consisted of 87 patients with no recurrence and Group 2 comprised 30 patients that had recurrence during the follow-up. The mean pre-instillation urinary pH value was significantly lower in Group 2 than in Group 1 (5.89 vs. 5.37, p <0.001). The receiver operating characteristic analysis revealed that the cut-off value of urinary pH in predicting recurrence was 5.25. The patients with a urinary pH value of 5.25 or greater had significantly higher recurrence-free survival rates. The patients with higher urinary pH before a single instillation of mitomycin-C had better recurrence-free survival. Bladder cancer, Mitomycin-C, Single instillation, Urinary pH.

Management, Surveillance Patterns, and Costs Associated With Low-Grade Papillary Stage Ta Non–Muscle-Invasive Bladder Cancer Among Older Adults, 2004-2013

Low-risk non-muscle-invasive bladder cancer (NMIBC) is associated with extremely low rates of progression and cancer-specific mortality; however, patients with low-risk NMIBC may often receive non-guideline-recommended and potentially costly surveillance testing and treatment. To describe current surveillance and treatment practices, cancer outcomes, and costs of care for low-grade papillary stage Ta (low-grade Ta) NMIBC and identify factors associated with increased cost of care. This population-based cohort study identified 13 054 older adults (aged 66-90 years) diagnosed with low-grade Ta tumors in the Surveillance, Epidemiology and End Results-linked Medicare database from January 1, 2004, through December 31, 2013. Medicare claims data through December 31, 2014, were also reviewed. Data were analyzed from April 1 to October 6, 2021. Surveillance testing and treatment among patients with low-grade Ta NMIBC. The primary outcome was patterns in population-level surveillance and treatment practice over time among patients with low-grade Ta NMIBC. Secondary outcomes were recurrence (defined as receipt of subsequent transurethral resection of bladder tumor >3 months after index diagnosis of NMIBC and initial transurethral resection of bladder tumor), progression (defined as receipt of definitive treatment for bladder cancer), and costs of care. Among 13 054 patients who met inclusion criteria, 9596 (73.5%) were male and 3458 (26.5%) were female, with a median age of 76 years (IQR, 71-81 years). A total of 403 patients (3.1%) were Black, 120 (0.9%) were Hispanic, 12 123 (92.9%) were White, and 408 (3.1%) were of other races and/or ethnicities. Rates of surveillance cystoscopy increased over the study period (from 79.3% in 2004 to 81.5% in 2013; P = .007), with patients receiving a median of 3.0 cystoscopies per year (IQR, 2.0-4.0 per year). Rates of upper tract imaging (particularly computed tomography or magnetic resonance imaging) also increased over the study period (from 30.4% in 2004 to 47.0% in 2013; P < .001), with most patients receiving a median of 2.0 imaging tests per year (IQR, 1.0-2.0 per year). The use of urine cytologic testing or other urine biomarker assessment also increased (from 44.8% in 2004 to 54.9% in 2013; P < .001). Rates of adherence to current guidelines were similar over time (eg, a median of 4398 patients [55.2%] received ≤2 cystoscopies per year in 2004-2008 vs a median of 2736 patients [53.8%] in 2009-2013; P = .11), suggesting overuse of all surveillance testing modalities. With regard to treatment, 2250 patients (17.2%) received intravesical bacillus Calmette-Guérin, and 792 patients (6.1%) received intravesical chemotherapy (excluding receipt of a single perioperative dose). Among all patients with low-grade Ta NMIBC, 217 (1.7%) experienced disease recurrence and 52 (0.4%) experienced disease progression. The total annual median costs of low-grade Ta surveillance testing and treatment increased by 60% (from $34 792 in 2004 to $53 986 in 2013), with higher 1-year median expenditures noted among those with disease recurrence ($76 669) vs no disease recurrence ($53 909) at the end of the study period. In this cohort study, despite low rates of disease recurrence and progression, rates of surveillance testing increased during the study period. The annual cost of care also increased over time, particularly among patients with recurrent disease. Efforts to improve adherence to current practice guidelines, with the focus on limiting overuse of surveillance testing and treatment, may mitigate associated increasing costs of care.

Management, surveillance patterns, and costs associated with low-grade papillary (Ta) nonmuscle-invasive bladder cancer.

464 Background: Low-risk non-muscle invasive bladder cancer (NMIBC) is associated with extremely low rates of progression and cancer-specific mortality, however, these patients may often receive non-guideline recommended and potentially costly surveillance and treatment(s). We sought to describe current surveillance and treatment practices, oncologic outcomes, and cost of care for low-grade papillary (LG Ta) NMIBC and identify predictors of increased cost of care. Methods: This population-based cohort study identified 13,054 patients diagnosed with LG Ta tumors in the Surveillance, Epidemiology and End Results-Medicare linked database from January 1, 2004 through December 31, 2013. The primary outcome was to characterize trends in population-level surveillance and treatment practice patterns over time among LG Ta patients. The secondary outcomes were recurrence, progression, and costs of care. Results: Of the 13,054 patients who met inclusion criteria, 9,596 (73.5%) were male and 3,485 (26.5%) were female, with a median age of 76 (Interquartile Range (IQR): 71–81) years. Rates of surveillance cystoscopy increased over the study period (79.3% to 81.5%, p = 0.007) with patients undergoing a median of three cystoscopies per year (IQR: 2–4). Rates of upper tract imaging utilization also increased, namely the use of computed tomography (CT) or magnetic resonance imaging (MRI) (30.4% to 47%, p &lt; 0.001), with most patients undergoing a median of two imaging tests per year. Similarly, the use of urine cytology or other urine biomarkers also increased (44.8% to 54.9%, p &lt; 0.001). Rates of compliance with current guidelines decreased over time suggesting overutilization of all surveillance testing modalities. A total of 17.2% of patients received intravesical bacillus-Calmette Guerin (BCG) and 6.1% received intravesical chemotherapy (excluding single perioperative dose). Among all LG Ta patients, 1.7% and 0.4% experienced disease recurrence and progression, respectively. Total annual median costs of LG Ta surveillance and care increased 1.6-fold from $34,792 to $53,986 over the study period, with increased expenditures noted among those with disease recurrence ($53,909 and $76,669). Conclusions: Despite low rates of disease recurrence or progression, rates of surveillance testing increased during the study period. Annual cost of care increased over time, particularly among patients with recurrent disease. Efforts to improve adherence to current practice guidelines, with the focus on limiting overutilization of surveillance testing and overtreatment, may mitigate associated rising costs of care.

Adjuvant therapies for non-muscle-invasive bladder cancer: advances during BCG shortage.

Non-muscle-invasive bladder cancer (NMIBC) represents a significant global therapeutic challenge, particularly in the era of Bacillus Calmette-Guérin (BCG) shortage. High-risk NMIBC can progress to muscle invasive or metastatic disease in 25% of patients. Optimal treatment selection, according to risk stratification, is imperative. International guidelines slightly differ in their categorisation of low, intermediate and high-risk NMIBC. Nonetheless, a single post-operative instillation of chemotherapy with Mitomycin C (MMC) or Gemcitabine improves relapse-free survival (RFS) in low-risk NMIBC. Induction and maintenance intravesical BCG remains the historical gold standard for patients with intermediate or high-risk NMIBC. However, clinicians may be forced to consider alternatives given the current BCG shortage. Both intravesical MMC and Gemcitabine have been associated with similar efficacy to BCG, albeit in smaller studies. MMC may also be manipulated using a variety of methods to potentiate its effects. BCG treatment delivery may also be modified without affecting efficacy through dose reduction and abbreviation or omission of maintenance therapy. Preliminary data also highlight that directly proceeding to radical cystectomy may not adversely affect long-term quality of life measures. Access to new systemic and intravesical therapies must be prioritised for patients with BCG recurrent or unresponsive disease. When used in conjunction with molecularly defined biomarkers, these agents herald the potential for improved survival outcomes and alleviation of the current BCG shortage.

Prophylaxis of recurrence in low-to-intermediate risk non-muscle invasive bladder cancer (NMIBC)

Low- and intermediate-risk non-muscle invasive bladder cancer (NMIBC) is characterized by arelatively high risk of recurrence and adjuvant instillation therapy is considered standard of treatment for the majority of patients. To provide acurrent and in-depth review on the role of adjuvant therapy in low-to-intermediate risk NMIBC. APubMed-based search focusing on specific keywords (BCG, EORTC, early instillation, intermediate-risk, low-risk, mitomycin, NMIBC, recurrence) was conducted to identify studies published between 2000 and 2021. The corresponding publications were assessed based on their clinical relevance to the question at hand and their pro/retrospective approach. The EORTC risk tables are most frequently used to determine the risk of recurrence. In low-risk NMIBC, transurethral bladder tumor resection (TURBT) followed by early instillation is considered standard of treatment. In intermediate-risk NMIBC, TUR-BT is followed by adjuvant instillations with either chemoinstillation or BCG. Consequent use of adjuvant instillation therapy is necessary to reduce the risk of recurrence. New agents and modes of drug delivery (i.e.chemoablation) on the horizon have the potential to further improve outcomes.

742 Transurethral LASER Ablation (TULA): A Safe and Well Tolerated Procedure for The Treatment of Bladder Tumours Up To 4cm In Diameter in An Outpatient Setting

Abstract Aim Traditionally the management of recurrent non-muscle invasive bladder cancer (NMIBC) involves rigid cystoscopy and bladder biopsies/tumour resection under general/regional anaesthesia. As a result, many frail patients endure frequent anaesthetics and therefore are at increased risk of adverse outcomes including cognitive decline. Discontinuation of anti-platelet/anti-coagulation is not required for TULA. An outpatient TULA service was recently started at our trust. We present a case series of our first 4 months data. Method All TULA cases (n = 39) performed between Aug-Dec 2020 were included. Data was gathered prospectively including patient demographics, co-morbidities, initial cancer diagnosis and number of subsequent recurrences, post-procedural complications, and patient procedural satisfaction. Results Median age was 82 years (range 34-96) and median number of co-morbidities were 4 (range 0-10). Previous bladder cancer diagnosis was present for 85% with the most common initial stage G2pTa (n = 11). Median number of recurrences was 1 (range 1-5). Median patient perceived pain score was 3 (range 1-7) with 100% of patients preferring TULA over TURBT. Reasons included reduced procedural time (n = 18) and enhanced recovery (n = 15). Only 1 patient was readmitted post-procedure due to haematuria, however urine was clear after catheterisation and the patient was discharged. Conclusions TULA is safe for all low risk NMIBC, particularly for frail patients. It is well tolerated and facilitates improved patient experience. It also alleviates demand on theatre capacity and inpatient beds which has a positive effect on surgical waiting lists. Further audit of clinical outcomes should continue as recommended by NICE.

Mitofusin-2 Down-Regulation Predicts Progression of Non-Muscle Invasive Bladder Cancer.

Identification of markers predicting disease outcome is a major clinical issue for non-muscle invasive bladder cancer (NMIBC). The present study aimed to determine the role of the mitochondrial proteins Mitofusin-2 (Mfn2) and caseinolytic protease P (ClpP) in predicting the outcome of NMIBC. The study population consisted of patients scheduled for transurethral resection of bladder tumor upon the clinical diagnosis of bladder cancer (BC). Samples of the main bladder tumor and healthy-looking bladder wall from patients classified as NMIBC were tested for Mfn2 and ClpP. The expression levels of these proteins were correlated to disease recurrence, progression. Mfn2 and ClpP expression levels were significantly higher in lesional than in non-lesional tissue. Low-risk NMIBC had significantly higher Mfn2 expression levels and significantly lower ClpP expression levels than high-risk NMIBC; there were no differences in non-lesional levels of the two proteins. Lesional Mfn2 expression levels were significantly lower in patients who progressed whereas ClpP levels had no impact on any survival outcome. Multivariable analysis adjusting for the EORTC scores showed that Mfn2 downregulation was significantly associated with disease progression. In conclusion, Mfn2 and ClpP proteins were found to be overexpressed in BC as compared to non-lesional bladder tissue and Mfn2 expression predicted disease progression.