Adjuvant Intravesical Instillation Research Articles

Intra-arterial chemotherapy combined with BCG immunotherapy is more effective than intra-arterial chemotherapy plus intravesical chemotherapy or standard BCG immunotherapy in preventing the recurrence and progression of high-risk non–muscle-invasive bladder cancer

BackgroundUp to 45% of patients with high-risk non–muscle-invasive bladder cancer (NMIBC) will not benefit from adjuvant intravesical instillation. We aimed to introduce intra-arterial chemotherapy (IAC) to existing intravesical treatment and evaluate its feasibility and safety. Materials and methodsWe collected data from 170 patients who had been diagnosed with high-risk NMIBC and underwent transurethral resection of bladder tumor (TURBT) over the last 5 years. Twenty-seven patients were excluded according to specific exclusion criteria. The remaining 143 patients were divided into 3 groups according to their treatment: intravesical instillation of Bacillus Calmette – Guerin (BCG), BCG+ intra-arterial chemotherapy (IAC), and intravesical chemotherapy (IVC)+IAC groups. All groups received standard intravesical instillation of BCG or chemotherapeutic agents. In contrast, both the BCG+IAC and IVC+IAC groups received four courses of IAC (injection of cisplatin [60 mg/m2] and epirubicin [50 mg/m2] in the internal iliac arteries via Seldinger's percutaneous technique). ResultsThe median follow-up time was 47 months, ranging from 20 to 60 months. The restricted mean survival time (RMST), which represents the recurrence and progression rate of the BCG+IAC group, differed significantly when compared with the BCG group (P = 0.029 and 0.004, respectively) and the IVC+IAC group (P = 0.004 and 0.006, respectively). Kaplan-Meier plots revealed that the recurrence and progression-free survival of the BCG+IAC group were significantly higher than the BCG and IVC+IAC groups (P = 0.033 and 0.028, respectively). In contrast, the BCG and IVC+IAC groups showed similar RMST (P = 0.156 and 0.935, respectively), recurrence (P = 0.627), and progression-free (P = 0.931) survival. A small proportion of patients (20%) suffered from the adverse effects of IAC while 65% suffered from adverse reactions to intravesical instillation. Most adverse effects were ranked as grade I or II according to the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. ConclusionAnalysis showed that tumor recurrence and progression rate in the BCG+IAC group was lower than the BCG and IVC+IAC groups while patients in the IVC+IAC group suffered from milder adverse effects in cystitis and flu-like symptoms. Our findings may provide a new perspective for urologists when treating patients with high-risk NMIBC.

Epirubicin and Non-Muscle Invasive Bladder Cancer Treatment: A Systematic Review.

(1) Background: Intravesical chemotherapy is the standard of care in intermediate-risk non-muscleinvasive bladder cancer (NMIBC). Different agents are used across the world based on availability, cost, and practice patterns. Epirubicin (EPI), one of these agents, has been used by many centers over many decades. However, its true differential efficacy compared to other agents and its tolerability are still poorly reported. We aimed to assess the differential efficacy and safety of intravesical EPI in NMIBC patients. (2) Methods: This study aimed to systematically review the efficacy and safety profile of Epirubicin (EPI) in the management of non-muscle invasive bladder cancer (NMIBC) compared to other adjuvant therapies. A systematic search of the PUBMED, Web of Science, clinicaltrials.gov, and Google Scholar databases was conducted on 31 December 2023, using relevant terms related to EPI, bladder cancer, and NMIBC. The inclusion criteria targeted studies that evaluated patients treated with EPI following the transurethral resection of bladder tumors (TURBT) for NMIBC and compared oncological outcomes such as recurrence and progression with other adjuvant therapies, including Mitomycin C (MMC), Gemcitabine (GEM), and Bacillus Calmette-Guérin (BCG). Additionally, studies investigating the safety profile of EPI administered intravesically at room temperature and under hyperthermia, as well as oncological outcomes associated with hyperthermic intravesical EPI administration, were included. (3) Results: Eleven studies reported adverse events after adjuvant intravesical instillations with EPI; the most frequently reported adverse events included cystitis (34%), dysuria, pollakiuria, hematuria, bladder irritation/spasms, fever, nausea and vomiting, and generalized skin rash (2.3%). Nine studies compared EPI to BCG in terms of recurrence and progression rates; BCG instillations showed a lower recurrence rate compared to EPI, with limited or non-significant differences in progression rates. Two studies found no significant differences between EPI and MMC regarding progression and recurrence rates. One study showed statistically significant lower recurrence and progression rates with GEM in high-risk NMIBC patients. Another study found no significant differences between EPI and GEM regarding recurrence and progression. (4) Conclusions: EPI exhibits similar oncological performances to Gemcitabine and Mitomycin C currently used for adjuvant therapy in NMIBC. Novel delivery mechanisms such as hyperthermia are interesting newcomers.

Comparison of hyperthermic intravesical chemotherapy and Bacillus Calmette-Guerin therapy in high-risk non-muscle invasive bladder cancer: a matched-pair analysis.

To compare adjuvant hyperthermic intravesical chemotherapy (HIVEC) with mitomycin C and standard Bacillus Calmette-Guerin (BCG) therapy in terms of oncological outcomes and adverse events in patients with high-risk non-muscle-invasive bladder cancer (NMIBC). The data of patients with high-risk papillary NMIBC treated with adjuvant intravesical BCG instillations or HIVEC in our institution between June 2017 and August 2022 were analyzed retrospectively. Twenty-four patients who received HIVEC were matched 1:1 with patients receiving BCG therapy based on tumor characteristics (tumor stage and grade), age, gender, smoking status, and the number of tumors (single or multiple). HIVEC and standard BCG treatments were compared in terms of recurrence-free survival (RFS), progression-free survival (PFS), and adverse events. Forty-eight patients (24 in the BCG group and 24 in the HIVEC group) were included in the study. The median follow-up times of the BCG and HIVEC groups were 32 [interquartile range (IQR): 28.0-47.8] and 28 (IQR: 16.7-41.8) months, respectively (p = 0.11). There was no significant difference between the groups in terms of the 24-month RFS (BCG 83% vs HIVEC 88%, p = 0.64) and the 24-month PFS (BCG 100% vs HIVEC 94%, p = 0.61). Regarding the safety profile, at least one adverse event occurred in 13 (54%) of the patients in the BCG group and 12 (50.0%) of those in the HIVEC group (p = 0.77). This study demonstrated that HIVEC with mitomycin C has a similar oncological efficacy and safety profile to standard BCG therapy in high-risk NMIBC.

Body composition as a predictor of oncological outcome in patients with non-muscle-invasive bladder cancer receiving intravesical instillation after transurethral resection of bladder tumor.

Body status, categorized as sarcopenia or obesity and assessed using body mass index and body composition, affects the outcome of bladder cancer patients. However, studies comparing disease progression, recurrence, or overall survival in patients with non-muscle-invasive bladder cancer (NMIBC) with different body compositions are lacking. Therefore, we conducted a retrospective study to identify the impact of body composition, sarcopenia, and obesity on the oncological prognosis of patients with NMIBC who underwent transurethral resection of bladder tumor (TURBT) with Bacillus Calmette-Guerin (BCG) intravesical instillation (IVI). Patients with NMIBC who had undergone TURBT with adjuvant IVI with BCG from March 2005 to April 2021 were included. Body composition parameters were evaluated using computed tomography images of the third lumbar vertebrae and further categorized by sarcopenia and obesity. Oncological outcomes including recurrence-free survival (RFS), progression-free survival, and overall survival (OS) after treatment were analyzed. A total of 269 patients were enrolled. Subcutaneous adipose tissue (SAT) density was a significant predictor of RFS, whereas psoas muscle density was a significant predictor of OS in the multivariate analysis. Patients with sarcopenia but without obesity tolerated significantly fewer BCG IVIs than patients without sarcopenia or obesity. Patients with sarcopenia had poorer RFS and OS than those without sarcopenia. In contrast, patients with obesity had better OS than those without obesity. Body composition parameters, including SAT density and psoas muscle density, emerged as significant predictors of OS and RFS, respectively. Hence, our findings indicate that body composition is a helpful measurement to assess the oncological outcomes of patients with NMIBC.

Guidance of adjuvant instillation in intermediate-risk non-muscle invasive bladder cancer by drug screens in patient derived organoids: a single center, open-label, phase II trial

BackgroundIn intermediate-risk non-muscle invasive bladder cancer (NMIBC) clinical guidelines suggest an adjuvant instillation with a chemotherapeutic agent. However, the agent and regimen are not clearly defined. Worldwide, less than 15% of patients receive this adjuvant chemotherapeutic instillation. We recently developed a pipeline for the generation of patient derived organoids (PDO) in NMIBC. In this phase II trial, we aim to use our in vitro pipeline to select the most effective drug for chemotherapeutic instillation in NMIBC patients.MethodsPatients with first diagnosis of intermediate-risk NMIBC that are directed to transurethral resection of bladder tumor (TURBT) are enrolled. During TURBT, tumor is sampled, and specimens are directed to generate PDO. Once the PDO are formed, drug screens on them for Epirubicin, Mitomycin C, Gemcitabine and Docetaxel are performed. The drug with the highest antitumor activity in vitro will then be selected for 6 adjuvant intravesical instillations once weekly. Thereafter, patients are followed according to clinical guidelines by cystoscopy.DiscussionThe aim of this trial is to use drug screens in PDO to precise treatment selection for adjuvant instillation therapies in patients with intermediate-risk NMIBC. The ultimate goal of this trial is to reduce the risk of cancer recurrence. In the future, we aim to conduct clinical multicenter trials with an increased sample size, a broader panel of compounds and a focus on the reduction of cancer recurrence by precision delivery of care.Trial registration NCT05024734.

MP08-11 BODY COMPOSITION CAN PREDICT ONCOLOGICAL OUTCOME IN NON-MUSCLE INVASIVE BLADDER CANCER PATIENTS WHO RECEIVE INTRAVESICAL INSTILLATION WITH BACILLUS CALMETTE-GUERIN AFTER TRANSURETHRAL RESECTION OF BLADDER TUMOR

You have accessJournal of UrologyCME1 Apr 2023MP08-11 BODY COMPOSITION CAN PREDICT ONCOLOGICAL OUTCOME IN NON-MUSCLE INVASIVE BLADDER CANCER PATIENTS WHO RECEIVE INTRAVESICAL INSTILLATION WITH BACILLUS CALMETTE-GUERIN AFTER TRANSURETHRAL RESECTION OF BLADDER TUMOR Fan-Ting Liao, Liang-Kang Huang, Chun-Te Wu, Cheng-Keng Chuang, See-Tong Pang, Kai-Jie Yu, Po-Hung Lin, I-Hung Shao, Hung-Cheng Kan, Yuan-Cheng Chu, Ying-Hsu Chang, and Li-Jen Wang Fan-Ting LiaoFan-Ting Liao More articles by this author , Liang-Kang HuangLiang-Kang Huang More articles by this author , Chun-Te WuChun-Te Wu More articles by this author , Cheng-Keng ChuangCheng-Keng Chuang More articles by this author , See-Tong PangSee-Tong Pang More articles by this author , Kai-Jie YuKai-Jie Yu More articles by this author , Po-Hung LinPo-Hung Lin More articles by this author , I-Hung ShaoI-Hung Shao More articles by this author , Hung-Cheng KanHung-Cheng Kan More articles by this author , Yuan-Cheng ChuYuan-Cheng Chu More articles by this author , Ying-Hsu ChangYing-Hsu Chang More articles by this author , and Li-Jen WangLi-Jen Wang More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003223.11AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Review of previous literature showed still conflicted opinions on influence of obesity in bladder cancer (BC) prognosis, while high body mass index(BMI) being an independent risk factor of BC. This study was aimed to find out the impact of body composition, including sarcopenia and obesity, on the oncological prognosis of non-muscle invasive bladder cancer (NMIBC) patients receiving transurethral resection of bladder tumor (TURBT) with adjuvant intravesical instillation (IVI) with Bacillus Calmette-Guerin (BCG). METHODS: We retrospectively recruited patients with NMIBC who had received TURBT with adjuvant IVI with BCG from March 2005 to April 2021. Body composition parameters were evaluated according to analysis of computed tomography (CT) L3 images with artificial intelligence (AI) models and BMI, and was further categorized into sarcopenia and obesity groups. Oncological outcomes including recurrence-free survival (RFS), progression-free survival (PFS) and overall survival (OS) after treatment of TURBT with adjuvant IVI with BCG were analyzed using uni- and multivariate analysis. Impact of sarcopenia and obesity was analyzed with Kaplan-Meier survival exam. RESULTS: Total of 269 patients were enrolled. All patients were diagnosed with NMIBC and majority were Ta or T1, accounting for 44.6% and 50.9% respectively. Among them, 80 patients were sarcopenic and 53 were obese, accounting for 29.7% and 19.7% respectively. Subcutaneous adipose tissue density on CT was a significant predictor for RFS (p=0.011) and psoas muscle density also had significant impact on OS (p=0.044) in multivariate analysis. Sarcopenic or non-obese patients endured significantly fewer BCG IVI than non-sarcopenic or obese patients. Patients with sarcopenia had poorer RFS (p=0.030) and OS (p=0.033). In contrast, obese patients had better OS (p=0.008). CONCLUSIONS: In our study, we first demonstrated that body composition, sarcopenia, and obesity had significant impact on the RFS, PFS and OS in NMIBC patients. Non-sarcopenic and obese patients can significantly endure more BCG IVI and thus may result in superior oncological outcome. In patients with NMIBC, obese group had better OS while sarcopenic patients had worse OS and RFS. Body composition measurements has potentials in assessments of oncological outcomes of NMIBC patients. Source of Funding: No source of funding © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e98 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Fan-Ting Liao More articles by this author Liang-Kang Huang More articles by this author Chun-Te Wu More articles by this author Cheng-Keng Chuang More articles by this author See-Tong Pang More articles by this author Kai-Jie Yu More articles by this author Po-Hung Lin More articles by this author I-Hung Shao More articles by this author Hung-Cheng Kan More articles by this author Yuan-Cheng Chu More articles by this author Ying-Hsu Chang More articles by this author Li-Jen Wang More articles by this author Expand All Advertisement PDF downloadLoading ...

BCG shortage for intravesical instillation is associated with early tumoral recurrence in patients with high-risk non-muscle invasive bladder tumours

IntroductionDuring 2019 there was a worldwide shortage of BCG strains for intravesical instillation, limiting the availability of full dose schemes for maintenance courses. The main objective was to analyze the impact on tumoral relapse secondary to BCG shortage in our center. Secondary outcomes included recurrence and progression–free survival rates and tumoral relapse specific characteristics. MethodsRetrospective cohort study including 158 subjects (64 treated during 2019 and 94 during 2017) with high-risk non-muscle invasive bladder cancer and treated with a combination of Transurethral bladder resection (TURB) followed by adjuvant intravesical instillation with BCG in a tertiary hospital in Spain.Basal characteristics of both groups were analyzed. Times to event of interest (relapse; including recurrence and/or progression) were estimated with Kaplan–Meier survival analysis. Disease-free survival rates were analyzed using a multivariable Cox regression model of proportional hazards. ResultsMedian follow-up in the 2019 sample was 24 months and 50 months in the 2017 group with a median number of instillations of 8 and 12 respectively. Median time to relapse of 285 days (145–448) during 2019 and 382 days (215–567) in 2017 were observed (logRank p = 0.025). Further multivariable analysis revealed a proportional hazard ratio (HR) for disease-free survival rate of 1.87 (95% CI: 1.04–3.37 p = 0.036). No statistically significant differences in tumoral relapse characteristics were observed. ConclusionBCG shortage and subsequent reduced-dose schemes used for intravesical instillation due to limited availability, increase early tumoral relapse rates. These findings are consistent with available evidence, showing the need for full-dose BCG courses.

El desabastecimiento de BCG para instilación intravesical se asocia a la recidiva tumoral precoz en pacientes con tumor vesical no-músculo invasor de alto riesgo

IntroductionDuring 2019 there was a worldwide shortage of BCG strains for intravesical instillation, limiting the availability of full dose schemes for maintenance courses. The main objective was to analyze the impact on tumoral relapse secondary to BCG shortage in our center. Secondary outcomes included recurrence and progression–free survival rates and tumoral relapse specific characteristics. MethodsRetrospective cohort study including 158 subjects (64 treated during 2019 and 94 during 2017) with high-risk non-muscle invasive bladder cancer and treated with a combination of Transurethral bladder resection (TURB) followed by adjuvant intravesical instillation with BCG in a tertiary hospital in Spain.Basal characteristics of both groups were analyzed. Times to event of interest (relapse; including recurrence and/or progression) were estimated with Kaplan-Meier survival analysis. Disease-free survival rates were analyzed using a multivariable Cox regression model of proportional hazards. ResultsMedian follow-up in the 2019 sample was 24 months and 50 months in the 2017 group with a median number of instillations of 8 and 12 respectively. Median time to relapse of 285 days (145-448) during 2019 and 382 days (215-567) in 2017 were observed (logRank P=.025). Further multivariable analysis revealed a proportional hazard ratio (HR) for disease-free survival rate of 1.87 (95% CI: 1.04-3.37 P=.036). No statistically significant differences in tumoral relapse characteristics were observed. ConclusionBCG shortage and subsequent reduced-dose schemes used for intravesical instillation due to limited availability, increase early tumoral relapse rates. These findings are consistent with available evidence, showing the need for full-dose BCG courses.

Development and external validation of a novel nomogram model for predicting postoperative recurrence-free survival in non-muscle-invasive bladder cancer.

Transurethral resection of the bladder tumor with or without adjuvant intravesical instillation (IVI) has been the standard treatment for non-muscle-invasive bladder cancer (NMIBC), whereas a high percentage of patients still experience local tumor recurrence and disease progression after receiving the standard treatment modalities. Unfortunately, current relevant prediction models for determining the recurrent and progression risk of NMIBC patients are far from impeccable. Clinicopathological characteristics and follow-up information were retrospectively collected from two tertiary medical centers between October 2018 and June 2021. The least absolute shrinkage and selection operator (LASSO) and Cox regression analysis were used to screen potential risk factors affecting recurrence-free survival (RFS) of patients. A nomogram model was established, and the patients were risk-stratified based on the model scores. Both internal and external validation were performed by sampling the model with 1,000 bootstrap resamples. The study included 299 patient data obtained from the Affiliated Hospital of Xuzhou Medical University and 117 patient data obtained from the First Affiliated Hospital of Guangxi Medical University. Univariate regression analysis suggested that urine red blood cell count and different tumor invasion locations might be potential predictors of RFS. LASSO-Cox regression confirmed that prior recurrence status, times of IVI, and systemic immune-inflammation index (SII) were independent factors for predicting RFS. The area under the curve for predicting 1-, 2-, and 3-year RFS was 0.835, 0.833, and 0.871, respectively. Based on the risk stratification, patients at high risk of recurrence and progression could be accurately identified. A user-friendly risk calculator based on the model is deposited at https://dl0710.shinyapps.io/nmibc_rfs/. Internal and external validation analyses showed that our model had excellent predictive discriminatory ability and stability. The risk calculator can be used for individualized assessment of survival risk in NMIBC patients and can assist in guiding clinical decision-making.

Cáncer de vejiga

Bladder cancer is the ninth most frequent neoplasm in the world and the most frequent urinary tract cancer. The most important risk factor is tobacco use in addition to environmental exposure to carcinogens. The most habitual symptom is hematuria. Nonmuscle-invasive bladder cancer includes stages pTa and pT1, although they are two entities with different clinical courses. Their treatment involves transurethral resection (TUR) of the bladder and, depending on the risk stratification, adjuvant intravesical instillation of chemotherapy or immunotherapy as well. Nonmetastatic muscle-invasive bladder cancer is treated with a radical cystectomy and administration of perioperative cisplatin-based chemotherapy. In select cases, multimodal treatment for bladder preservation is an alternative. In metastatic disease, treatment is based on cisplatin-based chemotherapy, immunotherapy, and other new tyrosine kinase inhibitor (TKI) agents and conjugated antibodies.

Consecuencias del desabastecimiento de BCG para instilación endovesical y su efecto sobre la supervivencia libre de recurrencia en tumores vesicales no infiltrantes de alto riesgo

Objectives: During 2019 there was a worldwide shortage of BCG strains for intravesical instillation, limiting the availability of full dose schemes for maintenance courses. The main objective of the present study is to analyze whether patients affected during the shortage by reduced dose courses, are at a higher risk of tumor recurrence than those receiving full dose schemes. Methods: Retrospective cohort study with a total sample of 154 subjects (60 treated during 2019 and 94 during 2017) with high-risk non-muscle invasive bladder cancer and treated with a combination of Transurethral bladder resection (TURB) followed by adjuvant intravesical instillation with BCG. Basal characteristics of both groups were analyzed. Times to event of interest (relapse; including recurrence and/or progression) were estimated by survival analysis using the Kaplan-Meier method. Relapse-free survival rates were analyzed using a multivariable Cox regression model of proportional hazards. Results: Median follow-up in the 2019 sample was 503 days and 1197 days in the 2017 group, with a median number of instillations of 8 and 12 respectively. There was a 37.7% proportion of tumoral relapse observed in the 2019 group and 29.03% during 2017. Survival analysis revealed mean relapse-free follow-up of 683 days (95%CI 601.3-765.5) in the 2019 group and of 1359 days (95%CI 1244.3-1474) in 2017. Further analysis using LogRank test revealed observed differences to be statistically significant (p=0.02) Multivariable analysis revealed a proportional Hazard ratio (HR) for relapse-free survival rate of 2.2 (95% CI: 1.13-4.25; p=0.019) regarding the 2019 sample treated with a reduced-dose course. Conclusions: BCG shortage and the subsequent reduced-dose schemes used for intravesical instillation, due to limited availability, had a significant impact on tumor relapse rates during follow-up. These findings are consistent with other published studies and show the need for full-dose BCG courses in order to prevent higher relapse rates after TURB.

PD03-09 QUALITY CONTROL INDICATORS (QCIS) FOR TRANSURETHRAL RESECTIONS OF BLADDER TUMORS: CORRELATION OF QCIS WITH CLINICAL OUTCOME IN A BELGIAN MULTI-CENTER PROSPECTIVE REGISTRY

You have accessJournal of UrologyBladder Cancer: Non-invasive I (PD03)1 Apr 2020PD03-09 QUALITY CONTROL INDICATORS (QCIS) FOR TRANSURETHRAL RESECTIONS OF BLADDER TUMORS: CORRELATION OF QCIS WITH CLINICAL OUTCOME IN A BELGIAN MULTI-CENTER PROSPECTIVE REGISTRY Tim Muilwijk*, Murat Akand, Yannic Raskin, Cedric Jorissen, Lorenz Vanhoucke, Kathy Vander Eeckt, Siska Van Bruwaene, Ben Van Cleynenbreugel, Steven Joniau, and Frank Van Der Aa Tim Muilwijk*Tim Muilwijk* More articles by this author , Murat AkandMurat Akand More articles by this author , Yannic RaskinYannic Raskin More articles by this author , Cedric JorissenCedric Jorissen More articles by this author , Lorenz VanhouckeLorenz Vanhoucke More articles by this author , Kathy Vander EecktKathy Vander Eeckt More articles by this author , Siska Van BruwaeneSiska Van Bruwaene More articles by this author , Ben Van CleynenbreugelBen Van Cleynenbreugel More articles by this author , Steven JoniauSteven Joniau More articles by this author , and Frank Van Der AaFrank Van Der Aa More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000000823.09AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Quality control indicators (QCIs) can objectively evaluate guideline adherence. We assessed 6 QCIs, based on guideline recommendations, in the treatment of NMIBC using a prospective transurethral resection of bladder tumor (TURBT) registry in 3 Belgian centers and assessed whether these QCIs correlated with clinical outcome of patients. METHODS: TURBT procedures were collected using electronic case report forms (eCRFs) in a prospective TURBT registry in 3 centers between 06-2013 and 03-2017. Outcomes of interest were recurrence-free survival (RFS), overall survival (OS), and cystectomy-free survival (CFS). Six QCIs were assessed for their indication: complete resection status (CRS), repeat resection (re-TUR), presence of detrusor muscle (DM) in the resection specimen, single post-operative instillation of Mitomycin C (MMC), adjuvant intravesical instillation of BCG, and initial therapy ≤6 weeks after diagnosis. Kaplan-Meier plots were used for visualization of outcome data and log-rank to compare clinical outcome for each QCI. RESULTS: A total of 1350 TURBTs were collected, 1165 TURBTs met inclusion criteria for a total of 907 patients. Median follow up was 21.8 mo (IQR: 12.1-34.3). RFS, OS, and CFS at 4-year were 63.5% (95%CI: 59.7-67.5), 78.9% (95%CI: 75.2-82.8), and 93.1% (95%CI: 91.4-94.9) respectively. Scores on QCI were: CRS: 97.1%, re-TUR: 33.6%, DM: 45.8%, MMC: 69.6%, BCG: 39.6%, and timing ≤6 weeks 87.7%. The following QCIs had a significant impact on outcome: CRS on OS, and CFS; re-TUR on OS (Figure 1A), and CFS; MMC on RFS (Figure 1B); BCG on RFS (Figure 1C), and OS (Figure 1D). CONCLUSIONS: We demonstrate that we can assess QCIs (based onguideline recommendations) using a Belgian prospective multicenter TURBT registry. Furthermore, we demonstrate that the following QCIs were correlated with clinical outcome of patients: CRS, re-TUR, MMC, and BCG. Therefore, QCIs could be used to check guideline adherence, and allow for comparison between centers, with the ultimate goal of increasing guideline adherence. Source of Funding: NA © 2020 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 203Issue Supplement 4April 2020Page: e75-e75 Advertisement Copyright & Permissions© 2020 by American Urological Association Education and Research, Inc.MetricsAuthor Information Tim Muilwijk* More articles by this author Murat Akand More articles by this author Yannic Raskin More articles by this author Cedric Jorissen More articles by this author Lorenz Vanhoucke More articles by this author Kathy Vander Eeckt More articles by this author Siska Van Bruwaene More articles by this author Ben Van Cleynenbreugel More articles by this author Steven Joniau More articles by this author Frank Van Der Aa More articles by this author Expand All Advertisement PDF downloadLoading ...

Abstract 1932: Cationic amphiphilic drugs as a potential new treatment option for patients with high risk non-muscle invasive bladder cancer

Abstract Urothelial carcinoma of the bladder (UCB) is the fifth most common cancer in the western world. UCB present either as non-muscle-invasive BC (NMIBC) or as muscle-invasive carcinomas (MIBC). NMIBC is characterized by a high risk of recurrence and even progression to MIBC based on clinicopathological risk factors. Despite radical surgery and extensive chemotherapy, the outcome of MIBC patients is poor. High-risk NMIBC is treated with adjuvant intravesical instillations with Bacillus Calmette-Guérin (BCG). However, a substantial number of patients do not tolerate BCG or do not respond. Novel therapy for patients who do not tolerate BCG or in who are BCG unresponsive is a clear unmet clinical need. Drug repositioning of existing FDA-approved drugs could be a promising opportunity. Recently, cationic amphiphilic drugs (CADs), including commonly used antidepressants, antihistamines and antipsychotics were found to preferentially induce lysosomal cell death in transformed cells. In this study, we evaluated the potential anti-tumor efficacy and toxicity of these drugs in in vitro assays, in vivo preclinical models, and in and ex-vivo cultured patient-derived bladder cancer tissue slices. Treatment with CADs resulted in a significant dose-dependent decrease in proliferation and viability of multiple human UCB cell lines (a.o. RT4, TCC-SUP, and UM-UC-3) in vitro. Consistent with previous data regarding the ability of CADs to induce lysosomal membrane permeabilization in other solid cancer cells, we observed lysosomal puncta formation, which is a hallmark of lysosomal leakage. Strikingly, instillation of CADs in preclinical in vivo models of orthotopically growing human UM-UC-3 UCB resulted in a significant reduction in orthotopic as well as metastatic tumor burden. In line with these data, treatment of 39 patient-derived ex vivo cultured UCB slices with penfluridol resulted in significant anti-tumor responses ranging from complete regression to a significant reduction of the tumor.In vivo experiments revealed that normal mouse urothelium is not affected upon bladder instillation of CADs (weekly instillation of penfluridol for 5 weeks) in non-tumor bearing nude mice. In addition, penfluridol treatment of ex vivo cultured normal human urothelium only marginally affected the tissue. In conclusion, we demonstrated that CADs can target UCB cells and might be a promising novel approach for treatment of UCB. Citation Format: Geertje van der Horst, Arjanneke F. van de Merbel, Eline Ruigrok, Maaike H. van der Mark, Emily Ploeg, Marja Jäätelä, Janneke van Uhm, Rob C. Pelger, Chris H. Bangma, Joost Boormans, Gabri van der Pluijm, Ellen C. Zwarthoff. Cationic amphiphilic drugs as a potential new treatment option for patients with high risk non-muscle invasive bladder cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1932.

Quality Control Indicators for Transurethral Resection of Non-Muscle-Invasive Bladder Cancer.

Complete transurethral resection of bladder tumor (TURBT) is the initial procedure of choice for non-muscle-invasive bladder cancer, but its quality is far from optimal in clinical practice. We evaluated the existing body of evidence substantiating current quality control indicators (QCIs) for TURBT. A literature search was performed using PubMed and Embase, and selected articles were reviewed according to their level of evidence. Disease recurrence and progression were used as the primary end points. No hard evidence supports complete resection as a QCI, but rationally, it is the most important indicator for TURBT. A repeat resection is an important QCI in high-risk disease patients, but evidence suggests that it may not be necessary when detrusor muscle is present in the initial resection specimen. The presence of detrusor muscle in the resection specimen is a validated QCI for TURBT. Adjuvant intravesical instillation is a scientifically proven QCI. Bladder perforation is a controversial QCI in the existing literature. No evidence indicates the ideal time frame for the initial TURBT; thus, initial therapy in the first 6 weeks after diagnosis is not a good QCI. Three of the 6 proposed QCIs for TURBT are supported by evidence. Our literature analysis indicated the use of complete resection, repeat resection, the presence of detrusor muscle, and intravesical instillation are QCIs to minimize recurrence and progression, and increase beneficial outcomes.

583 - Neoadjuvant short-term intensive chemoresection vs. standard adjuvant intravesical instillations in NMIBC: Preliminary results on tolerability and adverse events

583 - Neoadjuvant short-term intensive chemoresection vs. standard adjuvant intravesical instillations in NMIBC: Preliminary results on tolerability and adverse events

Randomized study of intravesical pirarubicin chemotherapy with low and intermediate-risk nonmuscle-invasive bladder cancer in Japan: Comparison of a single immediate postoperative intravesical instillation with short-term adjuvant intravesical instillations after transurethral resection.

Purpose:The objective of this study was to evaluate the efficacy, defined by the 3-year tumor recurrence-free survival rate, of intravesical chemotherapy using pirarubicin (THP) in patients with low or intermediate-risk nonmuscle-invasive bladder cancer (NMIBC).Patients and methods:Between October 2010 and January 2015, 206 patients were enrolled, and finally 113 were randomized to receive either a single immediate postoperative intravesical instillation of THP (30 mg) (Group A), or 8 additional weekly intravesical instillations of THP (30 mg) after a single postoperative instillation (Group B). The patients were examined by performing cystoscopy and urine cytology every 3 months after transurethral resection to determine bladder tumor recurrence. The primary endpoint was 3-year-recurrence-free survival rate.Results:All 113 patients were bacillus Calmette–Guérin (BCG)-naïve. The 3-year recurrence free survival rate was 63.7% for Group A and 85.3% for Group B (log-rank test, P = .0070). In patients with intermediate recurrence risk, the 3-year recurrence-free survival rate was 63.4% in Group A and 86.1% in Group B (log-rank test, P = .0036). Cox regression analysis revealed that only additional instillation of THP was a significant independent factor for recurrence-free rate in patients with intermediate risk. No patient with progression was noted during this period. Frequent adverse effects (AEs) were frequent urination and micturition pain, and no severe AEs (Grade 3 or more) occurred.Conclusion:Additional instillation of THP (30 mg) weekly for 8 weeks reduced the risk of tumor recurrence without severe AEs in BCG-naïve NMIBC patients with intermediate risk.

PD66-11 HYPERTHERMIC INTRAVESICAL CHEMOTHERAPY FOR BCG-UNRESPONSIVE NON-MUSCLE INVASIVE BLADDER CANCER

You have accessJournal of UrologyBladder Cancer: Non-invasive III1 Apr 2018PD66-11 HYPERTHERMIC INTRAVESICAL CHEMOTHERAPY FOR BCG-UNRESPONSIVE NON-MUSCLE INVASIVE BLADDER CANCER Joep de Jong, Kees Hendricksen, Marloes Rosier, Joost Boormans, and Hugh Mostafid Joep de JongJoep de Jong More articles by this author , Kees HendricksenKees Hendricksen More articles by this author , Marloes RosierMarloes Rosier More articles by this author , Joost BoormansJoost Boormans More articles by this author , and Hugh MostafidHugh Mostafid More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2018.02.3007AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Adjuvant intravesical instillations with bacillus Calmette-Guerin (BCG) is the recommended treatment option for patients with intermediate and high-risk non-muscle invasive bladder cancer (NMIBC). Despite adequate BCG treatment, a large proportion of patients experiences a recurrence. Although radical cystectomy is the Gold Standard for BCG-unresponsive NMIBC, a number of patients are unfit for or unwilling to consider this option. The optimal therapy in such cases is unknown. The objective of the present study was to assess the efficacy of hyperthermic intravesical chemotherapy (HIVEC®) in BCG-unresponsive intermediate and high-risk NMIBC patients. METHODS From October 2014 to July 2017 NMIBC patients who were defined BCG-unresponsive (recurrence of high-grade disease after having had a minimum of 5/6 induction and 2/3 maintenance BCG instillations) were prospectively included at three academic institutions. All patients were planned to receive HIVEC® treatment, consisting of an induction phase followed by maintenance therapy. Only patients who had a minimum of 5 HIVEC® instillations were included in the present analysis. Patients were followed by cystoscopy and cytology every three months and a CT-scan yearly. The primary outcome was the recurrence-free survival (RFS). The Common Terminology Criteria for Adverse Events (CTCAE) was used to assess side-effects. RESULTS The study population consisted of 59 BCG-unresponsive NMIBC patients (8% intermediate- and 92% high risk) of whom 55 underwent ≥5 HIVEC® treatments. Histology was urothelial carcinoma in all patients and T-stage was pTis in 31, pTa in 10, pT1 in 9, pT1+CIS in 3 and pTa+CIS in two patients. The median age and follow-up was 72 years and 9.0 months [IQR 7.1 - 19.5]. The overall recurrence rate was 58% and the mean RFS was 16.6 months [SE 2.1] (Fig.1). In patients having carcinoma in situ (n= 36), the recurrence rate was also 58% and the mean RFS was 16.2 months [SE 2.8]. Progression occurred in 3 patients and two patients experienced severe side-effects (CTCAE >2). CONCLUSIONS HIVEC® seems a valid treatment option for BCG-unresponsive intermediate- or high-risk NMIBC patients. We report a mean RFS of >1 year, potentially avoiding or postponing the need for radical surgery in these patients. © 2018FiguresReferencesRelatedDetails Volume 199Issue 4SApril 2018Page: e1234-e1235 Advertisement Copyright & Permissions© 2018MetricsAuthor Information Joep de Jong More articles by this author Kees Hendricksen More articles by this author Marloes Rosier More articles by this author Joost Boormans More articles by this author Hugh Mostafid More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Low-Grade, Multiple, Ta Non-muscle-Invasive Bladder Tumors: Tumor Recurrence and Worsening Progression.

Nearly half of newly diagnosed cases of bladder cancer are low grade, noninvasive, and papillary tumors. The standard treatment for non-muscle-invasive bladder cancer (NMIBC) has been transurethral resection of the bladder tumor (TUR-BT) with or without adjuvant intravesical instillation (IVI) of chemotherapy or Bacillus Calmette-Guerin (BCG) therapy. NMIBC is known to be associated with high rates of recurrence and risk of progression. In this study, we have retrospectively analyzed the clinical outcome of initially diagnosed multiple low-grade Ta tumors, with a special focus on tumor recurrence and worsening progression (WP) pattern. We retrospectively reviewed 42 patients with primary, multiple, low-grade Ta bladder cancer. We defined WP as confirmed high-grade Ta, all T1 or Tis/concomitant CIS of bladder recurrence, upper urinary tract recurrence (UTR), or progression to equal to or more than T2. The associations between clinico-pathological factors and tumor recurrence as well as WP pattern were analyzed. Tumor recurrence and WP occurred in 23 (54.76%) and 8 (19.04%) patients during follow-up (median follow-up: 57.38months), respectively. WP to high grade/stage was seen in 8 patients. Multivariate analysis demonstrated that use of tobacco (p < 0.0001) and absence of IVI (p < 0.0001) were significant risk factors for tumor recurrence. The 5-year recurrence-free survival rate for non-tobacco users (74.0%) was significantly higher than that for tobacco users (42.5%, p = 0.0001), and also higher for patients receiving intravesical instillation (84.2 vs. 30.0% without IVI, p = 0.0001). Recurrence is common in patients with low-grade, Ta bladder cancer, especially in the setting of multiplicity. Recurrences occurred in 54.76% of patients and WP occurred in 19.04% of patients. Use of tobacco and non-use of IVI were strongly associated with high recurrence rate.

Processing techniques and safety analysis for transurethral resection of bladder lesions

Objective To evaluate the processing techniques and safety of ureteral stent after transurethral resection (TUR) of bladder lesions involving the ureteral orifice. Methods From January 2010 to August 2016, 42 cases of non-muscle invasive bladder tumor and 18 cases of glandular cystitis including 44 male and 16 female aged from 32 to 81 years(mean 55 years) were treated by TUR. Twenty-three cases of bladder tumor had single tumor and 19 cases had multiple tumors, and 37 cases were primary and 5 cases were recurrent. All the patients without preoperative hydronephrosis revealed by imageological examination.The lesions were resected into the deep muscle layer and involved ureteral orifice were resected during the procedure and after that a Double-J ureteral stent was placed in all cases.When looked for the ureteral orifice, we followed the ureteral peristalsis step by step, and found " concentric circles" muscle tissue.Then we used the guide wire as a guide for ureteral stenting. All the patients received one immediate intravesical instillation of 50 mg pirarubicin after TUR, and further scheme of adjuvant intravesical instillation was made according to the pathological diagnosis. Ureteral stents were removed 8~10 weeks after TUR, imageological examination were performed every three months. Results The operations were successful without complications. No serious adverse reaction occurred in adjuvant intravesical instillation chemotherapy. During the follow-up period of 4~60 months, no ureteral stricture and hydronephrosis occurred in all patients with ureteral stent, and the resected ureteral orifices recovered well with normal appearance and ejecting urine. Conclusions The ureteral orifice usually need to be removed during TUR for bladder lesions, and the way we following the ureteral peristalsis to resect the ureteral orifice is effective.Ureteral stenting after TUR of bladder lesions involving the ureteral orifice can prevent stricture at the ureterovesical junction without increasing the risk of tumor cell seeding along the upper urinary tract. Key words: Cystectomy; Urethra; Electrosurgery; Ureter

Hyperthermic Intravesical Chemotherapy for BCG Unresponsive Non-Muscle Invasive Bladder Cancer Patients.

Background:Adjuvant intravesical instillations with bacillus Calmette-Guérin (BCG) is the recommended treatment option for patients with intermediate-and high-risk non-muscle invasive bladder cancer (NMIBC). Despite adequate BCG treatment, a large proportion of patients experience a recurrence. Although radical cystectomy is the gold standard for BCG unresponsive NMIBC, some patients are unfit or unwilling to consider this option.Objective:To assess the effectiveness of Hyperthermic IntraVEsical Chemotherapy (HIVEC®) in BCG unresponsive NMIBC patients.Methods:A post-hoc analysis was conducted of prospectively included intermediate-and high-risk NMIBC patients who were planned to receive HIVEC® treatment between October 2014 and November 2017. For the present analysis, only patients who met the BCG unresponsive definition were included. Patients were followed by cystoscopy and cytology every 3 months and a CT-urography scan yearly. The primary outcome was the disease-free survival (DFS). The Common Terminology Criteria for Adverse Events (CTCAE) was used to assess side-effects.Results:The study population consisted of 55 BCG unresponsive NMIBC patients of whom 52 underwent≥5 HIVEC® treatments. The median age and follow-up were 73 years and 14.0 months (IQR 7.6 – 24.6). The median DFS was 17.7 months (SE 6.72) and progression occurred in four patients. The 1-year cumulative incidence rate of disease recurrence/progression was 53%. Two patients experienced severe side-effects (CTCAE≥3).Conclusions:HIVEC® seems a valid treatment option for BCG unresponsive NMIBC patients. We report a median DFS of 17.7 months (SE 6.72), potentially avoiding or postponing the need for radical surgery in a proportion of these patients.