Intravesical Instillation Of Mitomycin Research Articles

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.

PD32-07 BARRIERS TO SINGLE-DOSE INTRAVESICAL CHEMOTHERAPY IN NON-MUSCLE INVASIVE BLADDER CANCER: WHAT'S THE PROBLEM?

You have accessJournal of UrologyGeneral & Epidemiological Trends & Socioeconomics: Practice Patterns, Quality of Life and Shared Decision Making III (PD32)1 Apr 2020PD32-07 BARRIERS TO SINGLE-DOSE INTRAVESICAL CHEMOTHERAPY IN NON-MUSCLE INVASIVE BLADDER CANCER: WHAT'S THE PROBLEM? Clint Cary*, Laura Militello, Michael Weiner, Paige DeChant, Richard Frankel, and Michael Koch Clint Cary*Clint Cary* More articles by this author , Laura MilitelloLaura Militello More articles by this author , Michael WeinerMichael Weiner More articles by this author , Paige DeChantPaige DeChant More articles by this author , Richard FrankelRichard Frankel More articles by this author , and Michael KochMichael Koch More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000000896.07AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: 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. This led the American Urological Association 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 in studies and reasons for this are not well understood. METHODS: 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 influence clinician decision making about Mitomycin C use following (TURBT) in specific patient cases. Interview transcripts were coded using immersion/crystallization to identify emergent themes. RESULTS: 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 with identifying patients most likely to benefit. We identified significant cumbersome workflow processes and administrative barriers of postoperative chemotherapy following a TURBT. CONCLUSIONS: Workflow, fear, and value are key factors and also represent complexities of translating efficacy into effectiveness for a drug with known benefits to patients. Moving from efficacy to effectiveness requires understanding the context and environment in which the drug is going to be used. Areas of potential intervention development to improve the use of mitomycin C to reduce recurrence of bladder cancer are suggested. Source of Funding: NIH NCI K23 Award: 1K23CA212272 © 2020 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 203Issue Supplement 4April 2020Page: e639-e639 Advertisement Copyright & Permissions© 2020 by American Urological Association Education and Research, Inc.MetricsAuthor Information Clint Cary* More articles by this author Laura Militello More articles by this author Michael Weiner More articles by this author Paige DeChant More articles by this author Richard Frankel More articles by this author Michael Koch More articles by this author Expand All Advertisement PDF downloadLoading ...

Reasons for intravesical instillation postponement during adjuvant treatment of non-muscle-invasive bladder cancer: A prospective study

Intravesical instillations for adjuvant treatment of non-muscle-invasive bladder cancer (NMIBC) may be postponed of necessity. However, the frequency and reasons for postponement are unclear. We carried out a prospective, epidemiological study in an Urology department of the Île-de-France, between August 2016 and March 2017, to determine the frequency and reasons for postponement of intravesical instillations during adjuvant treatment of NMIBC. One-hundred consecutive patients treated by intravesical instillations of mitomycin C (MMC) or Bacillus Calmette-Guérin (BCG) were included. At each session and in case of instillation postponement, the medical team completed a specially designed questionnaire. A total of 541 instillations were performed in the 100 patients. Twenty-four instillations (4.4%) were postponed in 19 patients. The major cause of postponement was an untreated positive urine analysis and culture (UAC) in 13/24 (54%) cases. The causes of cancellation did not differ significantly between MMC and BCG. The most frequently cancelled instillations were the first in the therapeutic protocol in 26% of cases. The number of instillations preceding those cancelled did not differ significantly between MMC and BCG (2.1±2.0 instillations for MMC vs. 1.5±1.6 for BCG; P=0.64). There was a low rate of postponed instillations (4.4%). The main reasons, namely an untreated UAC and a positive dipstick test, based on the jurisprudence, are not included in the latest CC-AFU guidelines. 3.

Re: Value of an Immediate Intravesical Instillation of Mitomycin C in Patients with Non-muscle-invasive Bladder Cancer: A Prospective Multicentre Randomised Study in 2243 patients

Abstract Background The efficacy of an immediate single chemotherapy instillation after transurethral resection of a bladder tumour (TURBT) in patients with non–muscle-invasive bladder cancer (NMIBC) remains a topic of debate. Evidence is even more scarce when an immediate instillation is followed by adjuvant instillations. Objective To compare the effect of a mitomycin C (MMC) instillation within 24h to an instillation 2 wk after TURBT in patients with NMIBC with or without adjuvant instillations. Design, Setting, and participants Between 1998 and 2003, 2844 NMIBC patients were randomised for immediate versus delayed MMC instillation after TURBT. Patients were categorised in low-risk (LOR), intermediate-risk (IMR), and high-risk (HIR) groups. Total numbers of instillations in these groups were 1, 9, and 15, respectively. Outcome measurements and statistical analysis Primary end point was 3-yr recurrence risk for the IMR and HIR groups and 5-yr risk for the LOR group. Secondary outcomes were time to recurrence and incidence of adverse events. Analyses were performed with the log-rank test, Cox-regression, and χ 2 test in SPSS. Results and limitations A total of 2243 patients were eligible on an intention-to-treat basis. Recurrence risks were 43% and 46% in the LOR group (5-yr follow-up, p =0.11), 20% and 32% in the IMR group (3-yr follow-up, p =0.037), and 28% and 35% in the HIR group (3-yr follow-up, p =0.007), for an immediate and a delayed instillation, respectively. For all patients, the recurrence risk was 27% (95% confidence interval [CI], 24–30) in the immediate and 36% (95% CI, 33–39) in the delayed instillation group ( p p p =0.08). The risk groups in our study differ slightly from the current guidelines, which is a limitation of our study. Conclusions An immediate, single instillation after TURBT reduces the recurrence risk in NMIBC patients, independent of the number of adjuvant installations. Patient summary A single instillation of chemotherapy after the resection of non–muscle-invasive bladder cancer reduces the recurrence risk, even if patients are treated with an adjuvant schedule of instillations.

O4 - The value of an immediate intravesical instillation of mitomycin C in patients with nonmuscle-invasive bladder cancer: A prospective multicentre randomised study in 2243 patients

O4 - The value of an immediate intravesical instillation of mitomycin C in patients with nonmuscle-invasive bladder cancer: A prospective multicentre randomised study in 2243 patients

Value of an Immediate Intravesical Instillation of Mitomycin C in Patients with Non–muscle-invasive Bladder Cancer: A Prospective Multicentre Randomised Study in 2243 patients

BackgroundThe efficacy of an immediate single chemotherapy instillation after transurethral resection of a bladder tumour (TURBT) in patients with non–muscle-invasive bladder cancer (NMIBC) remains a topic of debate. Evidence is even more scarce when an immediate instillation is followed by adjuvant instillations. ObjectiveTo compare the effect of a mitomycin C (MMC) instillation within 24h to an instillation 2 wk after TURBT in patients with NMIBC with or without adjuvant instillations. Design, Setting, and participantsBetween 1998 and 2003, 2844 NMIBC patients were randomised for immediate versus delayed MMC instillation after TURBT. Patients were categorised in low-risk (LOR), intermediate-risk (IMR), and high-risk (HIR) groups. Total numbers of instillations in these groups were 1, 9, and 15, respectively. Outcome measurements and statistical analysisPrimary end point was 3-yr recurrence risk for the IMR and HIR groups and 5-yr risk for the LOR group. Secondary outcomes were time to recurrence and incidence of adverse events. Analyses were performed with the log-rank test, Cox-regression, and χ2 test in SPSS. Results and limitationsA total of 2243 patients were eligible on an intention-to-treat basis. Recurrence risks were 43% and 46% in the LOR group (5-yr follow-up, p=0.11), 20% and 32% in the IMR group (3-yr follow-up, p=0.037), and 28% and 35% in the HIR group (3-yr follow-up, p=0.007), for an immediate and a delayed instillation, respectively. For all patients, the recurrence risk was 27% (95% confidence interval [CI], 24–30) in the immediate and 36% (95% CI, 33–39) in the delayed instillation group (p<0.001) with a 27% reduction in relative recurrence risk (hazard ratio: 0.73, 95% CI, 0.63–0.85, p<0.001). The incidence of adverse events did not differ significantly between treatment groups (immediate instillation 25%, delayed instillation 22%, p=0.08). The risk groups in our study differ slightly from the current guidelines, which is a limitation of our study. ConclusionsAn immediate, single instillation after TURBT reduces the recurrence risk in NMIBC patients, independent of the number of adjuvant installations. Patient summaryA single instillation of chemotherapy after the resection of non–muscle-invasive bladder cancer reduces the recurrence risk, even if patients are treated with an adjuvant schedule of instillations.

Novel Multisensor Probe for Monitoring Bladder Temperature During Locoregional Chemohyperthermia for Nonmuscle-Invasive Bladder Cancer: Technical Feasibility Study

The effectiveness of locoregional hyperthermia combined with intravesical instillation of mitomycin C to reduce the risk of recurrence and progression of intermediate- and high-risk nonmuscle-invasive bladder cancer is currently investigated in clinical trials. Clinically effective locoregional hyperthermia delivery necessitates adequate thermal dosimetry; thus, optimal thermometry methods are needed to monitor accurately the temperature distribution throughout the bladder wall. The aim of the study was to evaluate the technical feasibility of a novel intravesical device (multi-sensor probe) developed to monitor the local bladder wall temperatures during loco-regional C-HT. A multisensor thermocouple probe was designed for deployment in the human bladder, using special sensors to cover the bladder wall in different directions. The deployment of the thermocouples against the bladder wall was evaluated with visual, endoscopic, and CT imaging in bladder phantoms, porcine models, and human bladders obtained from obduction for bladder volumes and different deployment sizes of the probe. Finally, porcine bladders were embedded in a phantom and subjected to locoregional heating to compare probe temperatures with additional thermometry inside and outside the bladder wall. The 7.5 cm thermocouple probe yielded optimal bladder wall contact, adapting to different bladder volumes. Temperature monitoring was shown to be accurate and representative for the actual bladder wall temperature. Use of this novel multisensor probe could yield a more accurate monitoring of the bladder wall temperature during locoregional chemohyperthermia.

Intravesical Instillation of Mitomycin C: A Cause of Delayed Bladder Perforation?

We present a case of bladder perforation secondary to intravesical instillation of mitomycin C following transurethral resection of bladder tumour (TURBT) and the role of early detection leading to successful conservative management. We also review the key relevant literature.

Long-term experience with early single Mitomycin C instillations in patients with low-risk non-muscle-invasive bladder cancer: prospective, single-centre randomised trial

To study the benefits of a single, early, intravesical instillation of mitomycin C(MMC) after transurethral bladder resection (TURB) in patients with low-risk non-muscle-invasive bladder cancer (NMIBC). In this prospective randomised single-centre trial, 211 patients with primary and low-risk tumours were enrolled between 2000 and 2009. Patients were randomly allocated to receive MMC intravesically within 24h of TUR or no further treatment. The primary end point was recurrence rate reduction. A total of 202 patients (97 in the MMC group and 105 in the control group) remained for analysis after exclusions. Median age was 61years (IQR 42-78), and median follow-up was 90months (IQR 3-112). No significant differences for patients' characteristics were observed between the two groups. During the study period, 10% (10/97) of the patients in the MMC group and 43% (46/105) in the control group experienced a recurrence (P=0.0001). Four patients in the MMC group and 11 (P=0.008) in the control group experienced an early recurrence (within 2years). One patient in the control group presented a tumour progression (T2G3). MMC treatment was associated with a 31% absolute risk reduction of recurrence and a 3.26 numbers needed to treat to prevent one recurrence. In this single-centre, long-term follow-up, experience a single, early instillation of MMC after TUR for low-risk NMIBC is associated with a significant reduction in risk of early and late recurrences.

Pseudoscleroderma possibly induced by intravesical instillation of mitomycin C

Pseudoscleroderma possibly induced by intravesical instillation of mitomycin C

Drug eruption due to intravesical instillations of both epirubicin and mitomycin C

We present the first patient to develop drug eruption due to intravesical instillations of both epirubicin and mitomycin C. A 58-year-old-man underwent transurethral resection (TUR) for superficial bladder carcinoma followed by instillations of intravesical chemotherapy. Immediately after TUR, the first instillation of epirubicin was performed. Two days after the first instillation, the patient developed generalized erythema of the face, trunk, upper and lower limbs. Two days after the second instillation, the patient developed severe generalized erythema and was diagnosed as having drug eruption due to intravesical instillations of epirubicin by the dermatologist. Instead of epirubicin, mitomycin C was instilled 2 weeks postoperatively. Two days after the first instillation of mitomycin C, the patient again developed severe generalized erythema and was diagnosed as having drug eruption due to intravesical instillation of mitomycin C. Drug eruption after the first instillation of epirubicin might have been due to drug toxicity of the agent. However, drug eruptions after the second instillation of epirubicin and the first instillation of mitomycin C might have been due to allergic reactions to the drugs. The patient has not received any further intravesical chemotherapy and has not demonstrated any such a drug eruption again.

Hämatogenes Kontaktekzem nach intravesikaler Instillation von Mitomycin C

Mitomycin C is an alkylating chemotherapeutic agent which is instilled intravesically to prevent recurrence of superficial bladder carcinomas. After several cycles of mitomycin C, our patient developed a pruritic genital dermatitis and palmar desquamation. Following exclusion of a fungal infection, we performed patch tests using the standard series, the major basic ointment ingredients, disinfectants, and mitomycin C in concentrations of 0.001 to 0.1%; the resulting diagnosis was allergic contact dermatitis due to delayed-type hypersensitivity to mitomycin C. The skin rash rapidly resolved with application of topical steroids, and the intravesical chemotherapy was changed to doxorubicin. Eczematous skin reactions are quite common side effects after intravesical instillation of mitomycin C. In the majority of cases, they are caused by delayed-type hypersensitivity reactions, presumably elicited by hematogenous spread of the allergen, and not by irritation. The sensitization most likely occurs via the bladder mucosa. In order to differentiate between allergic and toxic contact dermatitis, patch tests with the above-mentioned mitomycin C concentrations are useful. In cases of mild allergic contact dermatitis the intravesical chemotherapy might be continued with concomitant topical steroids.

Intravesical mitomycin C for superficial transitional cell carcinoma

Intravesical instillation of mitomycin C after a transurethral resection of a bladder tumor constitutes a standard treatment modality in the management of superficial transitional cell carcinoma in the urinary bladder. An immediate instillation of mitomycin C after transurethral resection has been shown to reduce the recurrence rate of superficial transitional cell carcinoma. Intravesical mitomycin C is generally considered to be a safe treatment option, but the past few years have seen the publication of a number of case reports on severe complications following mitomycin C instillation. This article reports on the mode of action, as well as the intravesical effects and current indications for mitomycin C instillation. This review will summarize the oncological benefits of mitomycin C in comparison with other intravesical treatments, such as bacillus Calmette–Guérin, and elucidate the incidence and types of possible complications associated with intravesical mitomycin C chemotherapy.

Immediate intravesical instillation of mitomycin C after transurethral resection of bladder tumor in patients with low-risk superficial transitional cell carcinoma of bladder.

The aim of this study was to evaluate the effect of immediate intravesical instillation of mitomycin C after transurethral resection of bladder tumor (TURBT) in patients with low-risk superficial transitional cell carcinoma (TCC). A total of 43 patients with low-risk superficial bladder cancer were randomly assigned into two groups after the surgery; 22 patients in group 1 were treated by immediate instillation of mitomycin C after TURBT, and 21 patients in group 2 received placebo. The two groups were compared using urine cytology and cystoscopy during the 24 postoperative months. Recurrence within the first 3 months was reported in none of the patients in group 1 and 5 in group 2 (P = .02). Of these, 4 had recurrence of tumor in the primary site. At 12 and 24 months, there were 1 patient (4.5%) in group 1 and 8 (38.1%) in group 2 with recurrence (P = .007). We had no patients with multifocal recurrence in group 1, but 3 (14.2%) in group 2. Nine-month tumor-free survival rate was 95% in group 1. Three-, 6-, 9-, and 12-month tumor-free survival rates in group 2 were 76%, 71%, 66%, and 62%, respectively (P = .007). None of the patients in group 1 and 3 in group 2 (14.3%) experienced some degrees of tumor progression (P = .06). Immediate instillation of mitomycin C after TURBT seems to be effective in the recurrence reduction and increase of recurrence-free interval at least in short term.

A Randomized Prospective Study Comparing Long-Term Intravesical Instillations of Mitomycin C and Bacillus Calmette-Guerin in Patients with Superficial Bladder Carcinoma

A Randomized Prospective Study Comparing Long-Term Intravesical Instillations of Mitomycin C and Bacillus Calmette-Guerin in Patients with Superficial Bladder Carcinoma

Radiation tolerance of normal mouse bladders after intravesical chemotherapy

The aim of this study was to compare functional damage in normal mouse bladder after various initial intravesical therapies and to investigate tolerance to subsequent irradiation. Six consecutive weekly intravesical instillations of Mitomycin C (MMC) or doxorubicin (DOX) were used as the initial therapy. Irradiation with single doses of 10–25 Gy (X-rays) was given at 4 or 12 weeks after intravesical treatment: Functional bladder damage was assessed from changes in the micturition frequency, expressed as frequency index (FI, number of urination events/ml urine in a 24-h test period) and from cystometry measurements of bladder volume at 52–56 weeks. Irradiation alone caused a temporary acute response (increased FI) within the first 4 weeks and a progressive late response starting from 15 to 37 weeks, depending on the radiation dose. A reduced bladder capacity was also evident at 52–56 weeks after 25 Gy. Intravesical MMC or DOX caused a 3-fold increase in FI during intravesical therapy with recovery to control levels within 2–3 weeks after cessation of treatment. Irradiation 4 weeks after MMC, or 4 or 12 weeks after DOX resulted in acute responses very similar to irradiation alone. There was no difference in time of onset or extent of late bladder damage when irradiation was given after DOX, compared with irradiation alone as assessed from repeated measurements of FI or cystometry at 52–56 weeks. In contrast, irradiation 12 weeks after MMC led to a decrease in acute radiation response compared with X-rays alone. In addition, the onset of late increases in FI was delayed (almost doubled) after pretreatment with MMC and there was no decrease in bladder volume at 52–56 weeks after irradiation compared with untreated controls. These data suggest that bladder tolerance to irradiation was not compromised by either of these drugs and may have even been improved by MMC.

Effect of different local and systemic therapy upon urinary bladder cytology.

1,900 cytological analyses of urine and bladder washings were made in 127 patients with urothelial bladder carcinomas before, during and after therapy. Following transurethral resection, all patients were treated by intravesical instillation of mitomycin C or thiotepa. Because of a locally advanced bladder carcinoma, 26 patients who were not candidates for radical cystectomy were given an integrated treatment of radiotherapy and chemotherapy. Intravesical administration of mitomycin C and thiotepa as well as integrated radiotherapy and chemotherapy induce a variety of cytological effects (toxic and/or metabolical) which may lead to cytological misinterpretations in the follow-up. DNA measurements by means of single-cell spectrocytophotometry show that the cytological effects induced by the above-mentioned therapies are not accompanied by an increase in the nuclear DNA content. It is concluded that the knowledge of these induced effects is mandatory for a correct interpretation of urinary cytology in the follow-up. Considering these effects and the clinical history, bladder carcinoma recurrences during and after intravesical chemotherapy or integrated radiotherapy and chemotherapy may be detected early by urinary cytology in the hands of an experienced cytopathologist or urologist. Furthermore, alterations of the urinary cytology occur after systemic application of cyclophosphamide and under immunosuppressive therapy.

A phase II study of intravesical mitomycin C in the treatment of superficial bladder cancer.

Twenty-three patients with histologically proven superficial bladder cancer (Tis, Ta, T1) were treated with intravesical instillations of Mitomycin C at a dose of 20 mg in 20 ml of water 3 times weekly for 21 instillations. Seventeen patients (77%) showed complete disappearance of all known disease and a further 4 showed partial responses. In 8 patients toxic effects developed (thrombocytopaenia 1, chemical cystitis 2, skin rash 3, urinary tract infection 2). All resolved rapidly on stopping the treatment but were severe enough in 5 patients to prevent them from receiving a full course of treatment.

Intravesical instillation of mitomycin C in the prophylactic treatment of recurring superficial transitional cell carcinoma of the bladder.

Twenty-six patients with an elevated recurrence rate of stage O or A bladder tumours were treated prophylactically after transurethral resection (TUR) with short-term intravesical instillations of mitomycin C in a non-randomised study. The data before intravesical chemotherapy (IVC) were taken as the internal control for each patient. Mitomycin C was administered in one course of 10 daily doses of 40 mg, starting 24 to 48 hours after TUR. The average follow-up was 13.9 months before and 28.5 months after IVC. Before IVC, the average number of recurrences was 2.6, with an average recurrence rate of 1 every 5.3 months. After IVC there was no tumour recurrence in 4 patients, with a mean of 12.2 months' follow-up, but there was tumour recurrence in 22 patients. For 17 patients (77%) the free interval averaged 2.3 times longer than the mean interval of recurrence before IVC and for 18 patients (82%) the recurrence rate averaged 3.3 times less than the recurrence rate before IVC.