Instillation Of Mitomycin Research Articles

MP63-12 THE EFFECTS OF SEQUENTIAL MITOMYCIN AND BACILLUS CALMETTE-GUÉRIN TREATMENT VERSUS BACILLUS CALMETTE-GUÉRIN MONOTHERAPY IN PATIENTS WITH HIGH-RISK NON-MUSCLE INVASIVE BLADDER CANCER: MITO-BCG (EUDRACT-2017-004540-37)

You have accessJournal of UrologyCME1 Apr 2023MP63-12 THE EFFECTS OF SEQUENTIAL MITOMYCIN AND BACILLUS CALMETTE-GUÉRIN TREATMENT VERSUS BACILLUS CALMETTE-GUÉRIN MONOTHERAPY IN PATIENTS WITH HIGH-RISK NON-MUSCLE INVASIVE BLADDER CANCER: MITO-BCG (EUDRACT-2017-004540-37) Cosimo DE Nunzio, Costantino Leonardo, Antonio Carbone, Antonio Luigi Pastore, Riccardo Lombardo, Antonio Nacchia, Antonio Cicione, Beatrice Turchi, Giorgia Tema, and Andrea Tubaro Cosimo DE NunzioCosimo DE Nunzio More articles by this author , Costantino LeonardoCostantino Leonardo More articles by this author , Antonio CarboneAntonio Carbone More articles by this author , Antonio Luigi PastoreAntonio Luigi Pastore More articles by this author , Riccardo LombardoRiccardo Lombardo More articles by this author , Antonio NacchiaAntonio Nacchia More articles by this author , Antonio CicioneAntonio Cicione More articles by this author , Beatrice TurchiBeatrice Turchi More articles by this author , Giorgia TemaGiorgia Tema More articles by this author , and Andrea TubaroAndrea Tubaro More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003321.12AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Aim of our study was to evaluate recurrence free survival of sequential Mitomycin and Bacillus Calmette-Guérin (BCG) treatment versus BCG monotherapy in patients with High risk Non-Muscle Invasive Bladder Cancer. METHODS: MITO-BCG is an open-label phase 4 study designed to evaluate the efficacy and safety of the sequential MMC and BCG combination treatment in patients with high-risk NMIBC. Eligibility criteria: males with a diagnosis of High risk NMIBC (T1 tumor, G3, CIS, or multiple and recurrent and large (>3 cm) Ta, G1G2 tumors or patients in the last EAU recurrence category EAU/EORTC recurrence score ≥10), age >40 years and <75 years, ability of consent. Patients are randomized in two groups: first with BCG induction treatment according to the standard protocol (an instillation once a week for six weeks) with 81 mg Connaught strain BCG and second receiving BCG treatment with the same protocol with a 40 mg mitomycin instillation the day before. Response will be assessed using cystoscopy and urine citology every 12 weeks for 2 years. Primary end points are recurrence rate; secondary end points are overall toxicity. RESULTS: The protocol study started on March 2019. Nowadays we enrolled 72 patients with a median age of 67 (IQR 59/73). Overall, 41 (57%) patients were randomized in the group of sequential combination therapy and 31 (43%) in the group of monotherapy with BCG. Mean Follow-up was 71±50 months. In BCG group 6/31 (19%) presented a recurrence while 10/41 (24 %) presented a recurrence in the combination group (p=0,611). On Cox regression analysis no differences were recorded in terms of recurrence when comparing both groups (HR: 1,23 95% CI: 0,46-3,50; p=0,640) (Figure). During follow-up only one patient experienced progression. Only 9 patients experienced adverse events with 8/9 grade I and one grade 4 (orchiectomy). No statistically significant differences were recorded in terms of complications between groups. CONCLUSIONS: The interim analysis of the Mito-BCG study suggests no differences in terms of recurrence free survival when comparing BCG alone vs sequential Mitomicin and BCG treatment. Both treatments present good and comparable tollerability. Source of Funding: None © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e876 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Cosimo DE Nunzio More articles by this author Costantino Leonardo More articles by this author Antonio Carbone More articles by this author Antonio Luigi Pastore More articles by this author Riccardo Lombardo More articles by this author Antonio Nacchia More articles by this author Antonio Cicione More articles by this author Beatrice Turchi More articles by this author Giorgia Tema More articles by this author Andrea Tubaro More articles by this author Expand All Advertisement PDF downloadLoading ...

The effect of immediate neoadjuvant electromotive instillation of mitomycin C with Bacillus Calmette-Guérin versus BCG alone in non-muscle-invasive bladder cancer: A randomized controlled trial.

The clinical effect of neoadjuvant intravesical instillation of chemotherapy immediately before transurethral resection of bladder tumors (TURBT) has been a subject of recent research. The aim of this study was to assess the effect of immediate neoadjuvant electromotive instillation of mitomycin C before transurethral resection for patients with non-muscle-invasive urothelial bladder cancer. Our study was a randomized clinical trial carried out on 50 patients diagnosed with non-muscle-invasive urothelial bladder cancer. Patients were classified into two groups: Group I consisted of 25 patients who received neoadjuvant electromotive drug administration of mitomycin C before TURBT and intravesical bacille Calmette-Guerin (BCG) per week for 6 weeks; Group II consisted of 25 patients who were treated with TURBT followed by intravesical BCG per week for 6 weeks alone (standard of care). Patients were followed up at 3, 6, 12, and 18 months by cystoscopy. Patients who received neoadjuvant electromotive drug administration of mitomycin C before TURBT in combination with BCG had a low recurrence rate compared with those who received BCG alone (12.0% vs. 48.0%, respectively; p=0.012) and a longer disease-free interval (88.0% vs. 52.0%, respectively; p=0.012). Four patients developed progression to muscle-invasive disease (16.0%) in the BCG alone group. However, this difference was not statistically significant (p=0.516). Regarding adverse effects, there were no statistically significant differences between the groups. Neoadjuvant intravesical electromotive drug administration of mitomycin C before TURBT is safe; reduces recurrence rates and enhances the disease-free interval compared with TURBT followed by BCG alone.

Quality Control Indicators for Transurethral Resection of Bladder Tumor: Results from an Embedded Belgian Multicenter Prospective Registry

BackgroundQuality control indicators (QCIs) can be used to objectively evaluate guideline adherence and benchmark quality among urologists and centers. ObjectiveTo assess six QCIs for non–muscle-invasive bladder cancer (NMIBC) using a prospective registry of transurethral resection of bladder tumor (TURBT) procedures. Design, setting, and participantsClinical data for TURBT cases were prospectively collected using electronic case report forms (eCRFs) embedded in the electronic medical record in three centers during 2013–2017. Pathological data were collected retrospectively. Patients with T0 disease or prior T2 disease were excluded. Outcome measurements and statistical analysisWe assessed six QCIs: complete resection (CR) status, presence of detrusor muscle (DM), re-TURBT, single instillation of mitomycin C (MMC), start of bacillus Calmette-Guérin (BCG) therapy, and therapy ≤6 wk after diagnosis. We assessed the quality of reporting on QCIs and compliance with QCIs, compared compliance between centers and over time, and investigated correlation between compliance and recurrence-free survival (RFS). Results and limitationsData for 1350 TURBT procedures were collected, of which 1151 were included for 907 unique patients. The distribution of European Association of Urology risk categories after TURBT was 271 with low risk, 464 with intermediate risk, and 416 with high risk. The quality of reporting for two QCIs was suboptimal, at 35% for DM and 51% for BCG. QCI compliance was 97% for CR, 31% for DM, 65% for MMC, 33% for re-TURBT, 39% for BCG, and 88% for therapy ≤6 wk after diagnosis. Compliance with all QCIs differed significantly among centers. Compliance with MMC and re-TURBT increased significantly over time, which could be attributed to one center. Compliance with MMC was significantly correlated with RFS. The main study limitation is the retrospective collection of pathology data. ConclusionsA TURBT registry consisting of eCRFs to collect pathology and outcome data allowed assessment of QCIs for NMIBC. Our study illustrates the feasibility of this approach in a real-life setting. Differences in performance on QCIs among centers can motivate urologists to improve their day-to-day care for patients with NMIBC, and can thus improve clinical outcomes. Patient summaryOur study demonstrates that quality control indicators for treatment of bladder cancer not invading the bladder muscle can be evaluated using electronic medical records. We assessed results for 1151 procedures in 907 individual patients to remove bladder tumors between 2013 and 2017 at three centers in Belgium. Compliance with the quality control indicators differed between centers, increased over time, and was correlated with recurrence of disease.

Corneal Perforation after Excision of Pterygium and Instillation of Mitomycin C: About an Observation

Pterygium is a common eye condition that predominates in warm, dry areas. It is a benign condition whose treatment is essentially surgical especially for advanced stages. But it is characterized by its tendency to recurrence from where the interest of the use of adjuvant treatments namely mitomycin C. Although this is relatively harmless serious and potentially blinding complications can occur. The authors report one case of complicated pterygium surgery with late perforation.

Mitomycin c can minimize corporal scarring following explantation of an infected penile implant

Delayed replantation following extrusion of an infected penile implant is hindered by the corporal scarring that issues. This renders the procedure difficult and with a higher rate of complications. In addition to the anti-tumour anti-biotic properties of Mitomycin C, it is known to be a potent anti-fibrotic agent with multiple applications in surgery such as esophageal atresia and bladder neck strictures. This work aims to evaluate the efficacy and safety of Mitomycin instillation upon removal of infected implants in preventing or minimizing corporal scarring Twelve patients with infected penile implants were included in the study. Upon extraction of the infected implant, corporal bodies were irrigated with antibiotics and antiseptics. This was followed by instillation of Mitomycin C, 10 mg in 250 cc saline, 125 cc into each cavernous space. Caution was observed to prevent contact with corporotomy and skin edges. The latter were freshened and closed. Re-implantation was performed 10-12 weeks subsequently. Four patients received an inflatable 3-piece implant and eight received a malleable. The cavernous cavity was found preserved, though tunica albuginea was thickened in all cases. Corporal dilatation was without resistance, using blunt Hegars. Ten patients received the same size of implant in length and girth. Two cases received a shorter implant (1 cm in one patient and 1.5 in the other). No re-infection, extrusion or urethral injuries were encountered. Two patients exhibited superficial skin ulcerations that resolved with topical care over 6-8 months. Mitomycin C instillation upon explantation of an infected penile prosthesis minimizes corporal scarring. Patients should be warned as to the possibility of postoperative skin ulceration. We believe this can be prevented by implantation of a narrower girth if the tunica albuginea is evidently thickened. None

The clinical efficacy and safety of equipment-assisted intravesical instillation of mitomycin C after transurethral resection of bladder tumour in patients with nonmuscular invasive bladder cancer: A meta-analysis.

This review and meta-analysis aimed to systematically evaluate the clinical efficacy and safety of equipment-assisted intravesical instillation of mitomycin C (MMC) in patients with nonmuscular invasive bladder cancer (NMIBC) after transurethral resection of bladder tumour (TURBT). The Embase, PubMed, CNKI, CBM, WANGFANG, VIP, Cochrane Library, and Clinicaltrial.com databases were searched for articles published before April 2022. The experimental group was treated with intravesical instillation of MMC assisted by equipment, including radiofrequency-induced thermochemotherapy, conductive thermochemical therapy, electromotive drug administration, or locoregional hyperthermia. The control group was treated with simple MMC perfusion. The outcomes of interest in the meta-analysis were recurrence, progression, side-effects, gross haematuria, and bladder irritation. A total of 15 studies that enrolled 1,190 patients were included in the meta-analysis. Compared to that of the control group, device-assisted intravesical instillation of MMC significantly reduced both tumour recurrence (odds ratio [OR] = 0.32, 95% confidence interval [CI] [0.24, 0.42], P <0.00001) and progression (OR = 0.29, 95% CI [0.12, 0.67], P = 0.004). There were no significant differences between the two groups in terms of safety (OR = 1.21, 95% CI [0.66,2.21], P = 0.54), bladder irritation (OR = 1.06, 95% CI [0.72,1.55], P = 0.78), or gross haematuria (OR = 1.11, 95% CI [0.64,1.94], P = 0.72). Equipment-assisted intravesical instillation of MMC significantly reduced the recurrence and progression of patients with NMIBC who underwent TURBT and improved their quality of life. Given the significant heterogeneity in research quality and sample size among earlier studies, more prospective, multicentre, large sample randomized controlled trials are needed to supplement and verify this in the future.

Minimal Patient-Reported Side Effects for a Chemoablative Gel (UGN-102) Used as Frontline Treatment in Adults with Nonmuscle-Invasive Bladder Cancer

Optima II ("OPTimized Instillation of Mitomycin for Bladder Cancer Treatment," clinicaltrials.gov: NCT03558503) was a phase 2b trial evaluating a nonsurgical alternative as a primary treatment for nonmuscle-invasive bladder cancer (NMIBC). Patients received 6 weekly instillations of UGN-102, a mitomycin-containing reverse thermal gel. This is the first study to report on patient-reported side effects of UGN-102. Sixty-three patients enrolled in Optima II from 20 sites. Of these 63 patients, 44 were in the cohort completing a quarterly patient-reported outcome measure assessing side effects. Changes in side effects were evaluated using the Wilcoxon signed-rank test. Associations of 3-month outcomes with demographic and clinical characteristics were examined with regression, controlling for baseline values. Ten of 44 patients (23%) were interviewed after the trial to understand tolerability for future patients making treatment decisions. Transcripts were double-coded using standard methods. In the patient-reported outcome measure cohort (44), 61% were men, 57% aged 65+ years and 89% were non-Hispanic White. UGN-102 did not cause decrements in patient-reported urinary symptoms, bloating/flatulence or malaise at the primary endpoint of 3 months. Sexual function mildly worsened. Future health worries improved. Demographics were not correlated with changes. Clinically, sexual function was correlated with new NMIBC and bloating/flatulence was associated with transurethral resection of bladder tumor within 12 months. In interviews, patients appreciated a nonsurgical alternative, would recommend the gel to other patients and would choose the gel over surgery. A nonsurgical, chemoablative gel (UGN-102) used as a primary treatment for NMIBC offers a more patient-centered therapeutic approach than standard treatments.

MP54-06 LONGITUDINAL HEALTH-RELATED QUALITY OF LIFE OUTCOMES IN ADULTS WITH NON-MUSCLE-INVASIVE BLADDER CANCER RECEIVING A CHEMOABLATIVE GEL AS A PRIMARY TREATMENT (OPTIMA II: PHASE 2B, SINGLE ARM, OPEN-LABEL TRIAL)

You have accessJournal of UrologyCME1 May 2022MP54-06 LONGITUDINAL HEALTH-RELATED QUALITY OF LIFE OUTCOMES IN ADULTS WITH NON-MUSCLE-INVASIVE BLADDER CANCER RECEIVING A CHEMOABLATIVE GEL AS A PRIMARY TREATMENT (OPTIMA II: PHASE 2B, SINGLE ARM, OPEN-LABEL TRIAL) Angela Smith, Ramsankar Basak, Dana Mueller, Robert Lipman, Randall Teal, Alison Hilton, Kara Giannone, Myra Waheed, and Angela Stover Angela SmithAngela Smith More articles by this author , Ramsankar BasakRamsankar Basak More articles by this author , Dana MuellerDana Mueller More articles by this author , Robert LipmanRobert Lipman More articles by this author , Randall TealRandall Teal More articles by this author , Alison HiltonAlison Hilton More articles by this author , Kara GiannoneKara Giannone More articles by this author , Myra WaheedMyra Waheed More articles by this author , and Angela StoverAngela Stover More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002633.06AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Low-grade non-muscle-invasive bladder cancer (LG NMIBC) is treated with transurethral resection of the bladder tumor (TURBT), which can worsen health-related quality of life (HRQOL). The trial “OPTimized Instillation of Mitomycin for Bladder Cancer Treatment” (Optima II, clinicaltrials.gov: NCT03558503) is a Phase 2b, open label, multicenter trial evaluating a nonsurgical alternative as a primary treatment. Patients receive six weekly instillations of UGN-102, a mitomycin-containing reverse thermal gel. We report on HRQOL changes at the primary endpoint of 3 months. METHODS: Of 63 patients enrolled in the Optima II trial, 44 were in the HRQOL cohort and completed quarterly questionnaires (61% men, 57% age 65+, and 89% non-Hispanic White). Longitudinal changes were evaluated using the Sign test and correlations with demographic and clinical characteristics with regression. Ten patients (23%) were interviewed and transcripts were double-coded using standard methods. RESULTS: The chemoablative reverse thermal gel did not cause decrements in patient-reported urinary symptoms, bloating/flatulence, or malaise (Figure). Sexual function mildly worsened. Demographic and clinical characteristics were not correlated with HRQOL changes. By 3 months, 31/44 (70%) LG NMIBC patients achieved a complete response (negative endoscopic examination, cytology, and for-cause biopsy). In interviews, patients appreciated a nonsurgical alternative, would recommend the gel to other patients, and would choose the gel over TURBT. CONCLUSIONS: Adults with LG NMIBC receiving a nonsurgical, chemoablative gel as a primary treatment maintained their HRQOL through 3 months, and interviewed patients would recommend the gel to other patients. A Phase 3 trial is warranted. Source of Funding: Bladder Cancer Advocacy Network Patient Survey Network Award, supported by Urogen Pharma © 2022 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 207Issue Supplement 5May 2022Page: e928 Advertisement Copyright & Permissions© 2022 by American Urological Association Education and Research, Inc.MetricsAuthor Information Angela Smith More articles by this author Ramsankar Basak More articles by this author Dana Mueller More articles by this author Robert Lipman More articles by this author Randall Teal More articles by this author Alison Hilton More articles by this author Kara Giannone More articles by this author Myra Waheed More articles by this author Angela Stover More articles by this author Expand All Advertisement PDF DownloadLoading ...

Guidelines from the cancer committee of the French Association of Urology (CC-AFU) for adequate intravesical instillations of Mitomycin C, Epirubicin, and BCG for non-muscle invasive bladder cancer

Intravesical instillations of mitomycin C, epirubicin and BCG are considered as the standard treatment for most patients diagnosed with non-muscle invasive bladder cancer. These guidelines aim to optimize the adjuvant intravesical treatment in order to increase the efficacy and lower the morbidity associated with its administration. We conducted a daily practice survey, an online search of available national regulation recommendations and of published guidelines. A bibliography search in French and English using Medline® and Embase® with the keywords "BCG"; "mitomycin C"; "epirubicin"; "bladder"; "complication"; "toxicity"; "adverse reaction"; "prevention" and "treatment" was performed November 2021. Patient information should be given by the attending physician before the first intravesical instillation. A medical exam to look for specific contraindications is also mandatory to select adequate candidates. Intravesical instillations should be delivered in health-care centers where urologic endoscopic procedures are routinely performed. Attending urologist or specialized nurse should check for negative pretreatment urine test. Intravesical instillation can only be delivered after bladder catheter has been inserted in the bladder without any injury of the lower urinary tract. The pharmaceutical agent should be kept in the bladder for two hours. Finally, voiding within the 6hours following intravesical instillations should be done in the sitting position and the patient should drink at least 2liters of water per day for 2days. The delivery of intravesical instillations of mitomycin C, epirubicin and BCG should follow a standardized procedure for better efficacy and lower morbidity.

Dermatomiositis amiopática como primera manifestación de cáncer de uréter

Resumen Descripción del caso clínico: Varón de 79 años, consultó por episodio de angioedema facial sin otra sintomatología. A la exploración física presentaba eritema en cara y cuello, angioedema peripalpebral y máculas eritematosas en el dorso de las manos. Se realizó biopsia de lesión cutánea compatible con pápula de Gottron y para descartar enfermedad sistémica urografía por tomografía computarizada observando ureterohidronefrosis izquierda grado III por posible neoplasia ureteral. Estudio de extensión negativo. Se realizó nefroureterectomía izquierda laparoscópica e instilación endovesical de Mitomicina C, con resultados anatomo-patológicos de carcinoma papilar urotelial de alto grado multifocal. El paciente presentó una evolución posquirúrgica favorable, con mejoría de las lesiones dérmicas, pero a los 7 meses desarrolló múltiples metástasis siendo éxitus. Relevancia: La asociación de dermatomiositis con neoplasias es bien conocida, pero son pocos los casos descritos con malignidad urológica. El cáncer ureteral con dermatomiositis amiopática es extremadamente raro. Implicaciones clínicas: Es importante realizar un tamizaje de cáncer en pacientes que cursan con dermatomiositis para así tratarlos y mejorar su pronóstico. Conclusión: La dermatomiositis es un síndrome paraneoplásico raro que se asocia al cáncer ureteral de manera muy infrecuente. El tamizaje de cáncer en estos pacientes es muy importante para mejorar el pronóstico. El tratamiento quirúrgico de este tumor supuso la desaparición de las alteraciones cutáneas.

Trial-based Cost-effectiveness Analysis of an Immediate Postoperative Mitomycin C Instillation in Patients with Non–muscle-invasive Bladder Cancer

BackgroundBladder cancer imposes a significant public health burden on the European Union. There is a need for cost-effective treatment and follow-up regimens. ObjectiveTo assess the cost-effectiveness of immediate mitomycin C (MMC) instillation within 1 d after surgery compared to delayed MMC instillation within 2 wk after surgery with further adjuvant treatment, depending on the patient’s risk group. Design, setting, and participantsThis economic evaluation was based on a randomized controlled trial among 2243 Dutch patients with non-muscle-invasive bladder cancer (NMIBC) patients from a health care perspective over a 3-yr time period. Outcome measurements and statistical analysisThe treatment effect was measured as time to recurrence and recurrence-free survival. Missing effect data were imputed with multiple imputation. Health care utilization and related costs were estimated on the basis of treatment protocols for NMIBC patients in the Netherlands. Statistical uncertainty was estimated using bootstrapping and is graphically presented using cost-effectiveness planes and cost-effectiveness acceptability curves. Results and limitationsTime to recurrence was significantly longer for immediate MMC instillation (27.31 mo) than for delayed MMC instillation (24.97 mo), with an adjusted mean difference of 2.21 mo (95% confidence interval [CI] 1.58–2.84). The proportion of patients with recurrence-free survival was significantly higher after immediate MMC instillation (0.65) than after delayed MMC instillation (0.56), with an adjusted mean difference of 0.08 (95% CI 0.06–0.11). Total mean health care costs per patient were significantly lower for immediate MMC instillation (€22959) than for delayed MMC instillation (€24624), with an adjusted mean difference of −€1350 (95% CI −€1799 to −€900). The study is limited by the retrospective estimation of costs. ConclusionsThis trial-based cost-effectiveness analysis shows that from a health care perspective, immediate MMC instillation is more effective and less expensive compared to delayed MMC instillation. Patient summaryWe assessed the cost-effectiveness of immediate bladder instillation of mitomycin C after surgery to reduce the risk of recurrence after removal of the bladder tumor as compared to delayed instillation in a large Dutch population of patients with non–muscle-invasive bladder cancer. We found that immediate instillation was more effective and less expensive than delayed instillation. We conclude that immediate mitomycin C instillation is a cost-effective treatment for non–muscle-invasive bladder cancer.

TP7.2.3 The effect of immediate versus early instillation of mitomycin C after transurethral resection of bladder cancer: Is timing everything?

Abstract Introduction and Aims Almost three quarters of patients diagnosed with bladder cancer have non-muscle invasive disease. The European Association of Urology (EAU) guidelines recommend the use of intravesical instillation of Mitomycin C (MMC) to reduce the rate of recurrence. Methods A retrospective cohort analysis was carried out of all patients who underwent a TURBT between January 2016 and January 2019 in our Trust. A comparison of recurrence outcomes was investigated between patients who had immediate instillation of MMC (within 1 hours post-TURBT) versus early instillation (within 24 hours post-TURBT). Recurrence was assessed at 3 months cystoscopy and at 1 year follow-up. Results 201 patients were included. 100 underwent immediate MMC instillation (75% male, 25% female); 101 early instillation (72% male, 28% female). There was 11% recurrence (immediate) versus 13% (early) in instillation groups at 3 months. At first year, recurrence was seen in 12% (immediate) versus 14% (early) groups. Of these recurrences, there was an upstaging of tumour in 27% (immediate) versus 31% (early) at the 3 monthly follow-up and 25% (immediate) versus 28% (early) at the 1st year. The mean period of post-operative stay following initial TURBT was 0.8 days in the immediate versus 1.1 days in the early instillation groups. Conclusion Although no statistical differences were seen in this study, the results appear to favour immediate instillation of MMC after TURBT with respect to reduction in recurrence and upstaging rates. Post-operative length of stay in hospital was also shorter in patients who had an immediate MMC instillation.

Health-related quality of life outcomes in adults with nonmuscle-invasive bladder cancer receiving a mitomycin-containing reverse thermal gel as a primary treatment (Optima II: Phase 2b, single-arm, open-label trial).

270 Background: The standard of care for low-grade non‐muscle‐invasive bladder cancer (LG NMIBC) is transurethral resection of the bladder tumor, which can worsen health‐related quality of life (HRQOL). The “OPTimized Instillation of Mitomycin for Bladder Cancer Treatment” (Optima II, clinicaltrials.gov: NCT03558503) is a Phase 2b, open label, single arm, multicenter trial evaluating a nonsurgical alternative as a primary treatment. Patients receive six weekly instillations of UGN-102, a mitomycin-containing reverse thermal gel with a sustained release time of up to 8 hours. We report on HRQOL changes between baseline and the primary endpoint of 3 months. Methods: A total of 63 patients enrolled in the Optima II trial at 20 sites in the U.S. and 2 sites in Israel between October 2018 and October 2020. Of the 63 patients enrolled, 44 were in the HRQOL cohort and completed a quarterly questionnaire. The QLQ-NMIBC24 has six subscales (urinary symptoms, malaise, future health worries, bloating and flatulence, sexual functioning, and male sexual problems) and five single items (intravesical treatment issues, sexual intimacy, worry about contaminating partner, sexual enjoyment, and female sexual problems) assessed with 24 items. Items were rescaled to 0-100 and reverse-coded so that higher scores indicate worse symptom burden. Longitudinal score changes were evaluated using the Sign test. We examined demographic and clinical characteristics associated with HRQOL change scores with regression modeling. A p-value of ≤0.01 was used. Results: The HRQOL cohort was 61% men, 57% age 65+, and 89% non-Hispanic White. Clinically, most LG NMIBC patients had multiple tumors (88%) with prior NMIBC episodes (77%), and two or more prior transurethral resection of bladder procedures (TURBT) (85%). Approximately half (55%) had their most recent TURBT surgery within 12 months of trial enrollment. No patients had missing HRQOL data at baseline or the primary end point of 3 months. The chemoablative reverse thermal gel used as a primary treatment did not cause decrements in patient-reported urinary symptoms, bloating/ flatulence, malaise, fever, general health, or future health worries. Sexual function mildly worsened between baseline and 3 months, and abated by 6 months. Demographic and clinical characteristics were not correlated with HRQOL change scores. By 3 months, 31/44 (70%) LG NMIBC patients achieved a complete response (negative endoscopic examination, cytology, and for-cause biopsy) and 0 experienced a recurrence. By 12 months, 8/44 (18%) patients had a recurrence. Conclusions: Adults with LG NMIBC in a Phase 2b trial who received a mitomycin-containing reverse thermal gel with sustained release maintained their HRQOL through 3 months. A Phase 3 trial is warranted. Clinical trial information: NCT03558503.

The HELENA study: Hexvix\xae-TURB vs. white-light TURB followed by intravesical adjuvant chemotherapy\u2014a prospective randomized controlled open-label multicenter non-inferiority study

PurposePhotodynamic diagnosis and white-light TURB with adjuvant intravesical chemotherapy (ICT) is widely used in treatment of bladder cancer. This non-inferiority trial is designed to demonstrate non-inferiority regarding recurrence-free survival (RFS) of Hexvix® TURB followed by immediate instillation compared to white-light TURB with immediate instillation followed by maintenance ICT.MethodsBetween 07/2010 and 12/2016, 129 patients with EORTC intermediate risk non-muscle invasive bladder cancer treated with TURB were included in this multicentre phase III study. Patients were randomized and received either white-light TURB with immediate ICT followed by maintenance ICT (n = 62, 20 mg Mitomycin weekly for 6 weeks as induction phase, afterwards 20 mg/month for 6 months) or Hexvix® TURB with immediate ICT only (n = 67, 40 mg Mitomycin). Primary study endpoint was RFS after 12 months. Hexvix® TURB was counted as non-inferior to white light alone if the upper limit of the one-sided 95% confidence interval of hazard ratio was lower than 1.676. Due to the non-inferiority design, the per-protocol population was used as the primary analysis population (n = 113)ResultsMedian follow-up was 1.81 years. Hexvix® group showed more events (recurrence or death) than white-light group (19 vs. 10) resulting in a HR of 1.29 (upper limit of one-sided 95%-CI = 2.45; pnon-inferiority = 0.249). The ITT population yielded similar results (HR = 1.67); 3.18], pnon-inferiority = 0.493). There was no significant difference in overall survival between both groups (p = 0.257).ConclusionNon-inferiority of Hexvix® TURB relative to white-light TURB with maintenance Mitomycin instillation in intermediate risk urothelial carcinoma of the bladder was not proven. Hence a higher effect of maintenance ICT is to assume compared to a Hexvix®-improved TURB only, confirming its important role in patient treatment.

Continuous saline bladder irrigation after blue light transurethral resection of bladder tumor increases recurrence-free survival in low- to intermediate-risk non-muscle invasive bladder cancer

To evaluate the efficacy of Continuous Saline Bladder Irrigation (CSBI) after blue light transurethral resection of bladder tumor (TURBT) to prevent recurrence of low- to intermediate-risk Non-Muscle Invasive Bladder Cancer (NMIBC). We conducted a retrospective study including patients with low- to intermediate-risk NMIBC who underwent TURBT in two urological centers between January 2017 and December 2018. Each TURBT was performed using blue light after intravesical instillation of hexaminolaevulinic acid. The experimental group included patients who received CSBI while the control group included patients without CSBI. When practice, CSBI was started immediately after the surgery and was interrupted 24 hours thereafter. Low-risk NMIBC had a surveillance while intermediate NMIBC had 8 adjuvant endovesical instillations of Mitomycin. The primary endpoint was bladder tumor recurrence free-survival which was defined as the time between the initial TURBT and the date of TURBT for bladder recurrence. A total of 167 patients (median age: 71 years) were included: 20% female, 15% low-risk, 85% intermediate-risk NMIBC. CSBI was performed in 95 cases (57%). No complication related to irrigation was reported. Bladder recurrence was observed in 55 cases (32.9%): 22 (23.1%) in the CSBI group vs. 33 (45.8%) in the control group (P=0.002). Multivariate stepwise logistic regression analysis with backward selection revealed that CSBI (HR 0.47 [0.27-0.81]; P=0.006) and MMC (HR 0.55 [0.31-0.95]; P=0.034) were significantly associated with reduced risk of bladder recurrence. Continuous saline bladder irrigation reduced the risk of bladder recurrence after blue light TURBT in patients with low- to intermediate-risk NMIBC while being safe. Prospective randomized study is needed to confirm these results. 3.

Barriers to single-dose intravesical chemotherapy in non-muscle invasive bladder cancer: what's the problem?

The intravesical instillation of mitomycin C immediately following surgery for non-muscle invasive bladder cancer has been shown to be efficacious in reducing cancer recurrence. As a result, the American Urological Association adopted guidelines for non-muscle invasive bladder cancer care to support its use in low to intermediate risk patients. Despite this, urologists' use of this drug following transurethral resection of a bladder tumor (TURBT) has been reported as low as 5% or less. Our study objective was to better understand the barriers urologists experience in using mitomycin C. Semi-structured interviews were conducted with 13 practicing urologists at 4 geographically distinct practice locations throughout Indiana between 2017 and 2018. Cognitive task analysis was used to explore factors that influenced their clinician decision-making about Mitomycin C use following TURBT in specific patient cases. Interview transcripts were coded and analyzed using immersion/crystallization to identify emergent themes. The median age of the urologists interviewed was 44 (IQR 40-48). Eighty-five percent were male. Approximately 30% had completed urologic fellowship training; 62% were in private practice. Three major themes related to the use of mitomycin C emerged: cumbersome workflow processes, urologists' fears of side effects, and issues of identifying patients most likely to benefit. Workflow, fear, and value are key factors and also represent complexities of translating efficacy into effectiveness for a drug with known benefits to patients. Areas of potential intervention development to improve the use of mitomycin C to reduce recurrence of bladder cancer are suggested. Alternatives such as gemcitabine may also help overcome these barriers.

Expression of aquaporins 3 in low grade risk of recurrence primary bladder cancer.

Bladder cancer (BC) is one of the most frequent malignancy of the urinary tract. Recent studies demonstrated the role of aquaporins urothelial tumor cells (AQPs) as potential prognostic factor for tumor progression and invasion. In this study we investigated the AQP3 expression levels inside primary superficial (pTa) low grade bladder cancer, correlating with pathological parameters and clinical outcomes. We retrospectively analyzed tumor samples of 66 patients with diagnosis of superficial urothelial (pTa) bladder cancer between 1997 and 2007. All patients underwent transurethral bladder resection (TURB) and immediate single instillation of mitomycin C. All tumors samples were blindly reviewed by two expert anatomopathologists and only pTa low grade urothelial bladder cancer were included. Cancer recurrence was defined as the detection of bladder lesions during follow-up cystoscopy. AQP3-immunoreactive areas detected at immunohistochemical analysis were classified as AQP3 positive. Of these 60.6% of patients was detected as negative for AQP3 expression. Forty-two patients develop cancer recurrence during follow-up with a mean progression free survival of 16.44 months. The absence of reaction for AQP3 was observed 56% (9/16) tumor grading G1 and 62% (31/50) tumor grading G2. No correlation was observed with sexual gender, grading of tumor differentiation, and recurrence of cancer disease. Kaplan-Meier curves of disease-free survival (DFS) showed a significant separation (p = 0.028) between patients AQP3-positive and AQP3-negative. It was observed a mean DFS of 23.83 and 14.43 months respectively in absence and presence of AQP3 expression. AQP3 expression is related to disease-free interval (DFI) and the absence of AQP3 expression correlates with a late relapse. The expression of AQP3 does not provide a reproducible quantitative aspect. AQP3 are not suitable to forecast tumor cell behavior but they perform a role as regulator for tumor cell homeostasis and for additional therapeutic developments.

Loco-regional deep hyperthermia combined with intravesical Mitomycin instillation reduces the recurrence of non-muscle invasive papillary bladder cancer

Objectives To compare the therapeutic effects of locoregional deep hyperthermia combined with intravesical chemotherapy with those of intravesical chemotherapy alone in patients with intermediate-/high-risk non-muscle invasive bladder cancer (NMIBC). To evaluate the impact of thermal dose in hyperthermia treatment. Methods We analyzed data retrieved from the medical records of patients with intermediate-/high-risk NMIBC treated with intravesical mitomycin (IM group) or locoregional deep hyperthermia combined with intravesical mitomycin (CHT group) at a single tertiary care hospital between May 2016 and June 2019. The primary and secondary endpoints were the recurrence-free survival rate and progression-free survival rate, respectively. Thermal dose was evaluated and adverse events were also recorded. Results In total, 43 patients (CHT: 18 patients, IM: 25 patients) were enrolled. The median follow-up durations were 14 and 23 months, respectively. The recurrence rate at 12 months was significantly lower in the CHT group than in the IM group (11.1% vs. 44%, p = .048); this trend persisted at 24 months (CHT: 11.1%, IM: 48%; p = .027). The recurrence-free survival was also significantly higher in the CHT group than in the IM group (p = .028). No tumor recurrence was noted in patients who received a thermal dose of ≥4 CEM43. All adverse events were well tolerated, and there was no treatment-related mortality. Conclusions Intravesical chemotherapy combined with locoregional deep hyperthermia for intermediate-/high-risk papillary NMIBC can significantly decrease the recurrence rate relative to that observed after intravesical chemotherapy alone.

To Compare Frequency of Tumour Recurrence in Low Risk Transitional Cell Carcinoma of Bladder Between Single Dose Mitomycin C Instillation and Control Group

Background: Many regimes of intravesical therapy have been tried in attempt to reduce the recurrence rate of non muscle invasive bladder cancer, these generally require frequent attendance for instillation. Multiple non-comparative studies have demonstrated the favourable outcomes of the immediate treatment by instillation of mitomycin C after transurethral resection of bladder tumor (TURBT) in cases of non-muscle invasive Transitional Cell Carcinoma.Objective: To compare frequency of tumour recurrence in low risk transitional cell carcinoma of bladder between single dose Mitomycin C instillation and control group.Material and Methods: This study was conducted at urology departmentsaidu teaching hospital and Nawaz sharif kidney center swat. Study Design Quasi Experimental.Study Duration was (From: Feb 2018 to February 2019). Total 62 patients fulfilling the inclusion criteria were selected. Patient were divided between group A and B according to Non probability purposive sampling. TURBT was done in all patients. In those assigned to group A Mitomycin C 40mg was instilled through foleys catheter and clamped within 12 hrs of resection once haematuria has cleared. Mitomycin C was retained for 2 hrs and then foleys catheter was removed.Results: Mean age of patients in Group-A and in Group-B was 54.90±11.48 and 60.03±13.58 years respectively. In Group-A 1(3.2%) and in Group-B 9(29%) patients had recurrence after 3 months follow up time period. Recurrence rate of Group-B was significantly higher. i.e. (p-value=0.006).Conclusion: Results of this study showed the superiority of mitomycin C in patients with low risk non muscle invasive bladder cancer in terms of significantly lower recurrence rate as compared to that of control group. So, it can be said that single mitomycin C instillation significantly decrease recurrence in patients with low risk non muscle invasive bladder cancer.

A Comparative Study Between Single Dose &amp; Multiple Doses of Mitomycin-C in the Management of Transitional Cell Carcinoma of Urinary Bladder

Objectives: To find out the efficacy of post TURBT immediate single dose adjuvant intravesical Mitomycin C therapy in comparison with multi-dose regimen of Mitomycin C therapy in the management of superficial transitional cell carcinoma of the urinary bladder. Methods: Total 76 patients of bladder mass were included in the study who had undergone transurethral resection followed by immediate single instillation of Mitomycin C. After availability of histopathological examination report of resected tumor, those fulfill the selection criteria were randomized into two groups. One group (Group A) was the odd numbers of the patients who already received immediate single intravesical instillation of Mitomycin C and another group (Group B) even number of the patients who received single dose of intravesical instillation of Mitomycin C immediately with additional 5 instillations (1 week interval for 5 weeks) and in whom prospective follow-up could be completed within next 12 months Results: The effect of single intravesical instillation of 40 mg of Mitomycin C (Group A) within 24 hours of TURBT with that of multiple doses (six doses) of Mitomycin C (Group B) in similar dose was insignificant. Conclusion: The efficacy of MMC single dose was similar to MMC multi-dose regimen with insignificant difference of side effect among the two groups (0% versus 6.25%). Bangladesh Journal of Urology, Vol. 20, No. 2, July 2017 p.74-77