Intermediate Risk Nonmuscle Invasive Bladder Research Articles

PIVOT-006: A phase 3, randomized study of cretostimogene grenadenorepvec versus observation for the treatment of intermediate risk non-muscle invasive bladder cancer (IR-NMIBC) following transurethral resection of bladder tumor (TURBT).

TPS715 Background: Guidelines for Intermediate Risk Non-Muscle Invasive Bladder Cancer (IR-NMIBC) recommend adjuvant intravesical (IVE) therapy or surveillance. Despite this, 30–60% of patients still recur, and these Guideline recommendations are lacking level-1 evidence. Thus, there is a considerable gap in knowledge and an unmet medical need for improved therapies in the adjuvant setting. Cretostimogene Grenadenorepvec is an oncolytic adenovirus designed to preferentially replicate in and kill cancer cells. The vector is transcriptionally regulated by the E2F promoter that is up-regulated in retinoblastoma (Rb) pathway-defective tumor cells, common in most IR-NMIBC bladder tumors. Additionally, the virus is engineered to selectively express GM-CSF, in order to induce a robust systemic anti-tumor immune response. PIVOT-006 is an open-label, multi-center, randomized Phase 3 study designed to assess the efficacy and safety of intravesical Cretostimogene after TURBT versus TURBT alone. Methods: Eligibility criteria: age ≥18 years, Eastern Cooperative Oncology Group performance status of 0-2, histologically confirmed IR-NMIBC with absence of nodal or metastatic disease at screening. IR-NMIBC, as defined by American Urologic Association-Society of Urologic Oncology Guidelines on NMIBC, is either a Low Grade (LG) stage Ta tumor that recurs within 12 months of prior LG or High Grade (HG) bladder cancer, a solitary LGTa tumor >3cm in size, multifocal LGTa tumors, primary HGTa lesion < 3cm in size, or a LGT1 tumor. Participants will be stratified by receipt of perioperative chemotherapy and tumor grade. Pts (N~450) will be randomized 1:1 to receive intravesical Cretostimogene (Cohort 1) adjuvant to TURBT or TURBT alone (Cohort 2). Single dose perioperative intravesical chemotherapy at the time of TURBT is permitted. If intravesical NMIBC recurrence is noted in Cohort 2, participants will be eligible to receive intravesical Cretostimogene. In Cohort 1, intravesical Cretostimogene will be instilled in combination with n-dodecyl-B-D-maltoside (DDM, an inactive detergent) for 6 weekly doses during the induction phase, followed by 3 weekly maintenance cycles at months 3 and 6, and culminating in single intravesical doses at months 9 and 12. Primary disease assessments include serial cystoscopy, urine cytology, axial imaging, and centralized review of pathologic samples. The primary outcome measure is recurrence free survival. Secondary outcome measures include safety, tolerability, progression free survival, and time to next intervention. Exploratory outcome measures include patient-reported quality of life, biomarker analyses, coxsackie adenovirus receptor and E2F promoter expression, neutralizing antibodies, and markers of immunogenicity. Clinical trial information: Pending.

Guiding adjuvant instillation in intermediate-risk non-muscle invasive bladder cancer by drug screens in patient-derived organoids.

TPS711 Background: Recurrence rates in intermediate risk non-muscle invasive bladder cancer (NMIBC) are high and therefore, clinical guidelines recommend adjuvant instillations. However, the exact regimen with an exact number of instillations and the chemotherapeutic agent to be used are not clearly defined. During the last years we have established a standardized pipeline to generate patient-derived organoids (PDO) from cold cup biopsies of NMIBC. We showed that the subsequent organoids maintain key features of the parental tumor and share the molecular landscape. Moreover, our pipeline allows to investigate drug response to different agents in a standardized manner. Methods: In this ongoing, open-label, single center phase II trial, we aim to use drug screens in PDO of patients with intermediate risk NMIBC to guide drug selection for intravesical instillation. Patients with diagnosis of intermediate-risk NMIBC are enrolled. PDO are generated from biopsies prior transurethral resection of the bladder tumor. On the generated PDO drug response is determined to four chemotherapeutic agents that have already been used for bladder instillations in the literature (Epirubicin, Mitomycin C, Gemcitabine and Docetaxel). The most effective drug is selected for adjuvant instillation into the bladder once weekly for 6 instillations. The follow-up thereafter is performed according to European guidelines. The primary endpoint of the study is to determine the proportion of patients for which a specific selection of chemotherapeutic agent for intravesical instillation can be determined by using drug screens in PDOs. Secondary endpoints are recurrence- and, progression free survival, quality of life and translational studies. The null hypothesis, that a drug prediction will only be possible in 65% of patients, will be tested against a one-sided alternative. Assuming that the real proportion is 85%, 31 participants should show a statistically significant result at 5% significance and 80% power (exact binomial test). Due to early termination of 10%, a total number of 34 patients will be included. We are successfully conducting a trial to implement drug screens in PDO into daily routine and to guide patient treatment. This is a novel concept to precise treatment selection in patients with intermediate-risk NMIBC. When the primary endpoint is met, a modification of the trial with larger sample size, novel compounds and a focus oncological outcomes is foreseen. Clinical trial information: NCT05024734 .

P234 - Comparing toxicity and short term outcomes of Hyperthermic Intravesical Chemotherapy with Mitomycin-C versus Intravesical Chemotherapy with Mitomycin-C alone in the management of intermediate risk non-muscle invasive bladder cancer

P234 - Comparing toxicity and short term outcomes of Hyperthermic Intravesical Chemotherapy with Mitomycin-C versus Intravesical Chemotherapy with Mitomycin-C alone in the management of intermediate risk non-muscle invasive bladder cancer

138MO A randomized study to compare outcomes of intravesical chemohyperthermia with mitomycin C vs intravesical BCG for intermediate and high risk non-muscle invasive bladder cancer (NMIBC)

With the global shortage of bacillus Calmette-Guerin (BCG) coupled with the high recurrence rates of NMIBC, newer adjuvant intravesical treatment options are required. Although intravesical BCG remains the gold standard, the use of chemohyperthermia (CHT) as an alternative treatment is expanding all over the world. This study looks into the use of CHT with MMC as an alternative for BCG in NMIBC.

Oral 8 - Evaluating the effect of follow-up intensity on the outcomes for patients with intermediate risk non-muscle invasive bladder cancer

Oral 8 - Evaluating the effect of follow-up intensity on the outcomes for patients with intermediate risk non-muscle invasive bladder cancer

A0237 - A randomized study to compare outcomes of intravesical chemohyperthermia with mitomycin c vs. intravesical BCG for intermediate and high risk Non-Muscle Invasive Bladder Cancer (NMIBC)

A0237 - A randomized study to compare outcomes of intravesical chemohyperthermia with mitomycin c vs. intravesical BCG for intermediate and high risk Non-Muscle Invasive Bladder Cancer (NMIBC)

Alternating Cystoscopy with Bladder EpiCheck® in the Surveillance of Low-Grade Intermediate-Risk NMIBC: A Cost Comparison Model.

Bladder cancer surveillance is invasive, intensive and costly. Patients with low grade intermediate risk non-muscle invasive bladder cancer (NMIBC) are at high risk of recurrence. The objective of this model is to compare the cost of a strategy to alternate surveillance with cystoscopy and a urine marker, Bladder EpiCheck, to standard surveillance. A decision tree model was built using TreeAge Pro Healthcare to compare standard surveillance (Standard) with a modified surveillance incorporating Bladder EpiCheck. The model was based on 2 years of surveillance. Outcomes were obtained from literature. Costs were obtained from US and 9 European countries. Sensitivity analyses were performed. The efficacy of the model was equivalent in terms of recurrence for each arm with median recurrence rate of 22%. When setting marker price at 200 local currency, the marker arm was less expensive in the USA, Netherlands, Switzerland, Belgium, Italy, Austria and UK by 154€ to 329£ per patient, for a 2-year period. Cost was higher in France, Spain, and Germany by 33-103€. Cost parity was achieved with marker price between 148€ and $421. Marker cost and specificity have the greatest impact on the overall model cost. A strategy alternating the urine marker Bladder EpiCheck with cystoscopy in the surveillance of patients with low grade intermediate risk bladder cancer is cost equivalent in the US and European countries when the marker is priced 148€ -$421, as a result of the marker's high specificity (86%). Prospective studies will be necessary to validate these findings.

Low Risk of Severe Complications After a Single, Post-Operative Instillation of Intravesical Chemotherapy in Patients with TaG1G2 Urothelial Bladder Carcinoma.

EAU guidelines recommend a single instillation (SI) of intravesical chemotherapy (e.g. Mitomycin C) within 24 hours after transurethral resection of a bladder tumour (TURBT) in patients with low- to intermediate risk non-muscle invasive bladder cancer without (suspected) bladder perforation or bleeding requiring bladder irrigation. However, remarkable variation exists in the use of SI. The risk of severe complications is likely to contribute to this variation, but evidence is limited. To investigate the absolute severe complication and mortality risk after SI in low- and intermediate risk bladder cancer. In this observational, historic cohort study, data on 25,567 patients diagnosed with TaG1G2 urothelial bladder carcinoma (UBC) between 2009 and 2018 who underwent TURBT were collected from the Netherlands Cancer Registry. Data were supplemented with information on cause of death and severe complications after cancer treatment by re-examining the electronic health records and the 14-day complication risk and the 30-day mortality risk were evaluated. On average, 55% of patients had a SI after TURBT, varying from 0->80% between hospitals. The 30-day mortality risk was 0.02% and the 14-day risk of severe complications was 1.6%. As the absolute risk of mortality and severe complications is very low, SI after TURBT can be considered a safe treatment in patients with low- to intermediate UBC without contraindications for SI. These results imply that a part of eligible patients is denied effective treatment.

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.

Comparison of Single Monthly Instillations of Intra-Vesical Bacillus Calmette-Guerin Maintenance Therapy with Southwest Oncology Group Regimen in Non-Muscle Invasive Bladder Cancer Patients-A Retrospective Analysis In a Single Institute.

To compare the efficacy and complication rate of monthly instillations of Bacillus Calmette-Guerin (BCG) as maintenance therapy in intermediate and high risk Non-Muscle Invasive Bladder Cancer (NMIBC) patients with the current standard Southwest Oncology Group (SWOG) protocol. In this observational retrospective study, 40 intermediate and high risk NMIBC patients, receiving standard BCG maintenance regimen, were compared with another 40 NMIBC patients, undergoing monthly intra-vesical instillations of BCG with regard to recurrence, progression and major and minor adverse effects. The two groups were similar in their basic characteristics except for the older age in the monthly instillation group ( 70.95 ± 9.66 years vs. 64 ± 8.8, p = 0.001). Study objectives between the monthly instillation group and the standard group, including recurrence ( 17.5 % vs. 25%, p = 0.34) and progression rate ( 7.5% vs. 10%, p = 0.54) did not show statistically significant difference. Major and minor complication rate also did not show any difference between the two groups. In addition to the currently recommended standard protocol of BCG maintenance therapy, our study shows that the monthly regimen can be recommended in intermediate and high risk NMIBC patients without compromising the efficacy of the treatment.

PD12-02 COST-EFFECTIVENESS OF MAINTENANCE BCG FOR INTERMEDIATE AND HIGH RISK NON-MUSCLE INVASIVE BLADDER CANCER

INTRODUCTION AND OBJECTIVE:While guidelines support the use of maintenance BCG (mBCG) for intermediate and high risk non-muscle invasive bladder cancer (NMIBC), in an era of BCG shortage, careful c...

Salvage Hyperthermic Gemcitabine and Docetaxel Combination Chemotherapy After BCG Failure in Non-Muscle Invasive Bladder Cancer Patients

BACKGROUND: Bacillus Calmette-Guerin (BCG) is the recommended therapy for high and intermediate risk non-muscle invasive bladder cancer (NMIBC), but treatment failure is common. While a radical cystectomy is recommended after BCG failure, some patients desire bladder preservation and others are poor surgical candidates. Salvage chemotherapy treatments may be offered to this subgroup of patients. OBJECTIVE: To assess if combination, hyperthermic Gemcitabine and Docetaxel chemotherapy (GEM/DOCE) is a safe and effective salvage option for treating NMIBC. METHODS: Sixty patients who received our GEM/DOCE protocol between 2007–2017 were identified (51 BCG failures, 9 BCG naïve). This study measured overall treatment success, defined as no recurrence, progression, cystectomy, nor death due to bladder cancer. Kaplan-Meier curves were used to ascertain probability of treatment success. The log-rank test was used to identify factors associated with treatment success. RESULTS: Sixty patients received treatment with a median follow-up of 14.9 months. All patients completed the induction course with no significant adverse effects. Overall treatment success was 83% at first surveillance, 69% at 1 year, and 55% at 2 years in the entire cohort, and 90% at first surveillance, 74% at 1 year, and 56% at 2 years in the BCG-failure patients. All-cause and bladder-cancer-specific survival were both 97.9% at 1 year, 85.9% and 94.6% respectively at 2 years. Three patients underwent cystectomy at a median of 10.2 months, two of these were secondary to recurrences. Three patients had progression of their disease. CONCLUSIONS: Hyperthermic GEM/DOCE seems to be a well-tolerated salvage regimen that demonstrates a reasonable efficacy and warrants further investigation.

Cost-Effectiveness of Maintenance bacillus Calmette-Guérin for Intermediate and High Risk Nonmuscle Invasive Bladder Cancer.

While guidelines support the use of maintenance bacillus Calmette-Guérin for patients with intermediate and high risk nonmuscle invasive bladder cancer, in an era of bacillus Calmette-Guérin shortage we explored the cost-effectiveness of maintenance bacillus Calmette-Guérin. A Markov model compared the cost-effectiveness of maintenance bacillus Calmette-Guérin to surveillance after induction bacillus Calmette-Guérin for intermediate/high risk nonmuscle invasive bladder cancer from a U.S. Medicare perspective. Five-year oncologic outcomes, toxicity rates and utility values were extracted from the literature. Univariable and multivariable sensitivity analyses were conducted. A willingness to pay threshold of $100,000 per quality adjusted life year was considered cost-effective. At 5 years mean costs per patient were $14,858 and $13,973 for maintenance bacillus Calmette-Guérin and surveillance, respectively, with quality adjusted life years of 4.046 for both, making surveillance the dominant strategy. On sensitivity analysis full dose and 1/3 dose maintenance bacillus Calmette-Guérin became cost-effective if the absolute reduction in 5-year progression was greater than 2.1% and greater than 0.76%, respectively. On further sensitivity analysis full dose and 1/3 dose maintenance bacillus Calmette-Guérin became cost-effective when maintenance bacillus Calmette-Guérin toxicity equaled surveillance toxicity. In multivariable sensitivity analyses using 100,000 Monte-Carlo microsimulations, full dose and 1/3 dose maintenance bacillus Calmette-Guérin was cost-effective in 17% and 39% of microsimulations, respectively. Neither full dose nor 1/3 dose maintenance bacillus Calmette-Guérin appears cost-effective for the entire population of patients with intermediate/high risk nonmuscle invasive bladder cancer. These data support prioritizing maintenance bacillus Calmette-Guérin for the subset of patients with high risk nonmuscle invasive bladder cancer most likely to experience progression, in particular those who tolerated induction bacillus Calmette-Guérin well. Overall, our findings support the American Urological Association policy statement to allocate bacillus Calmette-Guérin for induction rather than maintenance therapy during times of bacillus Calmette-Guérin shortage.

The Role of Fluorescence In Situ Hybridization for Predicting Recurrence after Adjuvant bacillus Calmette-Guérin in Patients with Intermediate and High Risk Nonmuscle Invasive Bladder Cancer: A Systematic Review and Meta-Analysis of Individual Patient Data.

The objective of this study was to assess the value of fluorescence in situ hybridization to predict early recurrence in patients with nonmuscle invasive bladder cancer at intermediate and high risk treated with bacillus Calmette-Guérin. We performed a systematic review using MEDLINE®, Embase® and the Cochrane Library. Individual patient data from prospective observational studies of fluorescence in situ hybridization in patients treated with bacillus Calmette-Guérin were included. A 2-stage individual patient data meta-analysis was done to assess the value of fluorescence in situ hybridization to predict tumor recurrence after bacillus Calmette-Guérin induction therapy. From a total of 4 studies we obtained individual data on 422 patients, of whom 408 with a median followup of 18.8 months were included in the final analysis. When fluorescence in situ hybridization was positive, the recurrence HR was 1.20 (95% CI 0.81-1.79) before bacillus Calmette-Guérin (time 0), 2.23 (95% CI 1.31-3.62) at 6 weeks (time 1), 3.70 (95% CI 2.34-5.83) at 3 months (time 2) and 23.44 (95% CI 5.26-104.49) at 6 months (time 3). A positive fluorescence in situ hybridization test after bacillus Calmette-Guérin correlated with higher risk of recurrent tumor. Fluorescence in situ hybridization could aid urologists in risk stratifying and counseling patients. Based on the HR and the narrowest CI the preferred timing of fluorescence in situ hybridization is 3 months after transurethral resection of bladder tumor. This is also in time for patients in whom induction therapy fails to enter clinical trials or change the treatment strategy.

Comparison of Efficacy and Safety Between Postoperative Intravesical Instillation of Mitomycin-C and Continuous Saline Bladder Irrigation after TURBT in Non-muscle Invasive Bladder Cancers

Objective To critically analyse the efficacy and safety of continuous saline bladder irrigation versus single installation of mitomycin-C (MMC) after transurethral resection of bladder tumour (TURBT) in patients with low to intermediate risk non-muscle invasive bladder cancer. Materials and Methods The question in consideration best merits answer by critically reviewing and analyzing the literature and finally to provide the recommendation about the relevance of the conclusions from the literature. A search study identifies the relevant literature from the well-known academic databases in the context of the re-search question. The particular sets of the key words are used in different formats to search the literature. The literature has been thoroughly reviewed and analyzed for the strengths and limitations. Specific data was critically taken for analysis depending upon the type of literature articles with special reference to their usefulness, knowledge, attitudes, transferability, validity/reliability and strength of conclusions. Results A total of 6 papers meeting the inclusion criteria, which compared the results of the efficacy and safety between intravesical chemotherapy and continuous saline bladder irrigation (CSBI) were critically analyzed. Conclusion CSBI cannot replace MMC in terms of its efficacy in the prevention of recurrence and progression but because of the better safety profile can be used as an alternative in patients with low to intermediate risk bladder cancers after TURBT.

Intravesical BCG: where do we stand? Past, present and future

High and intermediate risk non-muscle invasive bladder cancer poses a real challenge for treatment. Approximately 70% of bladder cancer presents as non-muscle invasive and 20–25% will progress to muscle invasive disease. Recurrences occur in up to 70% but treatment options are limited. Intravesical bacillus Calmette–Guérin is still considered the bladder sparing treatment of choice despite its well documented pitfalls. This review considers how bacillus Calmette–Guérin has become the recommended treatment, its benefits and risks and the alternative options for treatment. Level of evidence: Not applicable for this multicentre audit.

MP15-18 SAFETY AND TOLERABILITY ANALYSIS OF HYPERTHERMIC INTRAVESICAL MITOMYCIN TO MITOMYCIN ALONE IN HIVEC I AND HIVEC II: AN ANALYSIS OF 307 PATIENTS

You have accessJournal of UrologyBladder Cancer: Non-invasive I1 Apr 2017MP15-18 SAFETY AND TOLERABILITY ANALYSIS OF HYPERTHERMIC INTRAVESICAL MITOMYCIN TO MITOMYCIN ALONE IN HIVEC I AND HIVEC II: AN ANALYSIS OF 307 PATIENTS Wei Shen Tan, Juan Palou, John Kelly, and HIVEC I and HIVEC II Clinical Trials Group Wei Shen TanWei Shen Tan More articles by this author , Juan PalouJuan Palou More articles by this author , John KellyJohn Kelly More articles by this author , and HIVEC I and HIVEC II Clinical Trials GroupHIVEC I and HIVEC II Clinical Trials Group More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2017.02.503AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES The Combat BRS system is a novel hyperthermia delivering device which allows temperature controlled delivery and re-circulation of HM via a urethral catheter using an external heat source. HIVEC I and II are two randomized control trials to determine if HM is superior to MMC alone in intermediate risk non-muscle invasive bladder cancer (NMIBC). We report safety and tolerability outcomes comparing the two treatment arms. METHODS HIVEC I and II are multi-centre, open-labeled randomized controlled trials recruiting patients from 25 Spanish and UK centers. The HIVEC I randomizes patients to either MMC, HM for 30 mins and HM for 60 mins (HM 60). Patients receive 4 once weekly treatments followed by 3 one monthly treatments. HIVEC II randomizes patients to MMC or HM 60 where both treatment arms receive 6 weekly treatments. Both trials use 40 mg MMC diluted in either 50 ml (HIVEC I) or 40 ml (HIVEC II) of sterile water. We compared all HIVEC I and II patients who were randomized to MMC (n=154) or HM 60 (n=153). HM was delivered by heating MMC to 43°C. Adverse events (AE) were reviewed by the independent data monitoring committee. HIVEC I and II were registered with EudraCT (2013-002628-18) and ISRCTN (23639415) respectively. RESULTS 307 patients were included for analysis. 88.9% and 94.8% of HM and MMC patients respectively completed inductive therapy. Reasons for stopping therapy in 17 HM patients include: MMC allergy (n= 11), urinary symptoms (n=2), pain (n=1), haematuria (n=1), pneumonia (n=1) and in 8 MMC patients include: MMC allergy (n=7) and angina (n=1). AE which led to early termination of treatment were Grade II. There was no significant difference in patients with AE between HM (n=78, 51%) and MMC (n=66, 42.9%) (p=0.154). Most AE were Grade =II (HM: 97.7%, MMC: 98.5%). There was no Grade >III related AE. There was no difference in pain (HM: 13.1% vs MMC: 8.4, p=0.190), dysuria (HM: 5.2% vs MMC: 6.5%, p=0.617), urgency (HM: 11.8% vs MMC: 3.9%, p=0.067), incontinence (HM: 3.3% vs MMC: 0.6%, p=0.097) and rash/ allergic reaction (HM: 7.8% vs MMC: 5.2%, p=0.327). HM treated patients were significantly more likely to develop urinary frequency (HM: 15.0% vs MMC: 5.8%, p=0.008), haematuria (HM: 11.8% vs MMC: 3.9%, p=0.010) and bladder spasm (HM: 6.5% vs MMC: 0.6%, p=0.006). CONCLUSIONS HM delivered using the Combat BRS system is safe and well tolerated. The majority of AE in the HM arm were low grade with urinary frequency and haematuria more common in HM in comparison to MMC treated patients. HM represents a safe and well tolerated intravesical treatment for NMIBC. © 2017FiguresReferencesRelatedDetails Volume 197Issue 4SApril 2017Page: e177 Advertisement Copyright & Permissions© 2017MetricsAuthor Information Wei Shen Tan More articles by this author Juan Palou More articles by this author John Kelly More articles by this author HIVEC I and HIVEC II Clinical Trials Group More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

MP13-05 A RANDOMIZED TRIAL COMPARING TWO DIFFERENT RETENTION PERIODS OF INTRAVESICAL PIRARUBICIN INSTILLATION FOR INTERMEDIATE RISK NON-MUSCLE INVASIVE BLADDER CANCER (NMIBC) AFTER TRANSURETHRAL RESECTION.

You have accessJournal of UrologyBladder Cancer: Non-Invasive I1 Apr 2016MP13-05 A RANDOMIZED TRIAL COMPARING TWO DIFFERENT RETENTION PERIODS OF INTRAVESICAL PIRARUBICIN INSTILLATION FOR INTERMEDIATE RISK NON-MUSCLE INVASIVE BLADDER CANCER (NMIBC) AFTER TRANSURETHRAL RESECTION. Ryoma Kurahashi, Yutaka Kasejima, Yoshiaki Kawano, Wataru Takahashi, Takahiro Yamaguchi, Ken-ichiro Tanoue, Hiroshi Sakakida, Junji Yatsuda, Youji Murakami, Yutaka Sugiyama, and Masatoshi Eto Ryoma KurahashiRyoma Kurahashi More articles by this author , Yutaka KasejimaYutaka Kasejima More articles by this author , Yoshiaki KawanoYoshiaki Kawano More articles by this author , Wataru TakahashiWataru Takahashi More articles by this author , Takahiro YamaguchiTakahiro Yamaguchi More articles by this author , Ken-ichiro TanoueKen-ichiro Tanoue More articles by this author , Hiroshi SakakidaHiroshi Sakakida More articles by this author , Junji YatsudaJunji Yatsuda More articles by this author , Youji MurakamiYouji Murakami More articles by this author , Yutaka SugiyamaYutaka Sugiyama More articles by this author , and Masatoshi EtoMasatoshi Eto More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2016.02.2486AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Anthracyclines are recommended reagents for one immediate intravesical instillation after transurethral resection (TUR) and additional adjuvant instillation in intermediate risk non-muscle invasive bladder cancer (NMIBC) to reduce the risk of recurrence. Pirarubicin (THP), an anthracycline analogue, is widely used reagent for intravesical instillation chemotherapy. Several studies have showed that THP can rapidly penetrate tumor tissue after intravesical instillation. Therefore long instillation time (e.g. 120 min) may not be required for its prophylactic effect against recurrence since it may reduce the risk of adverse events such as cystitis and hematuria without compromising its efficacy. However, there is no high level evidence regarding optimized intravesical THP instillation time in terms of both toxicity and efficacy. METHODS This randomized, prospective, open-label trial intended to enroll 160 pts with primary NMIBC with intermediate risk based on EORTC criteria. All pts received initial THP instillation within 24 hr after TUR and then intended to continue weekly repetitive THP instillation for a total of 9 treatments. Pts who seemed likely to be at intermediate risk were provisionally registered and then randomized into two groups with different intravesical THP retention times before TUR, (a) 30 min versus (b) 120 min. Follow-up period is 4 years. Primary endpoint is change from baseline in quality of life (e.g. OABSS and I-PSS), which will be evaluated prior to THP intravesical instillation. Secondary endpoint is recurrence-free survival. RESULTS 126 pts were enrolled for provisional registration in this trial and randomized before TUR-B. After excluding pts due to the result of pathology by TUR-B such as benign disease, T1 G3 tumor and concomitance of CIS, 29 pts were assigned to group (a) (30 min), and 26 pts to group (b) (120 min). There is a trend that group (a) is less prone to increase in OABSS after 3rd instillation compared to group (b), which is not statistically significant. Log-rank test shows that there is no significant difference in recurrence-free survival between the groups during follow-up period (HR=2.161, 95% C.I.: 0.4317-10.82, p=0.3484). CONCLUSIONS Shortening intravesical instillation period to 30 min has little effect on reducing the adverse effect of THP. However, it does not compromise the prophylactic effect on recurrence in intermediate risk NMIBC pts. © 2016FiguresReferencesRelatedDetails Volume 195Issue 4SApril 2016Page: e135-e136 Advertisement Copyright & Permissions© 2016MetricsAuthor Information Ryoma Kurahashi More articles by this author Yutaka Kasejima More articles by this author Yoshiaki Kawano More articles by this author Wataru Takahashi More articles by this author Takahiro Yamaguchi More articles by this author Ken-ichiro Tanoue More articles by this author Hiroshi Sakakida More articles by this author Junji Yatsuda More articles by this author Youji Murakami More articles by this author Yutaka Sugiyama More articles by this author Masatoshi Eto More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Combining Mitomycin C and Regional 70 MHz Hyperthermia in Patients with Nonmuscle Invasive Bladder Cancer: A Pilot Study

Despite intravesical therapy with immunotherapy or chemotherapy intermediate and high risk nonmuscle invasive bladder cancer is associated with a high risk of recurrence and progression to muscle invasive bladder carcinoma. While intravesical hyperthermia combined with mitomycin C has proved effective to treat nonmuscle invasive bladder cancer, there is less experience with invasive regional 70 MHz hyperthermia and mitomycin C. Therefore, we examined the safety and feasibility of this treatment combination for intermediate and high risk nonmuscle invasive bladder cancer. Between 2009 and 2011, 20 patients with intermediate and high risk nonmuscle invasive bladder cancer were treated with intravesical mitomycin C (40 mg) combined with regional hyperthermia. Treatment consisted of 6 weekly sessions followed by a maintenance period of 1 year with 1 hyperthermia-mitomycin C session every 3 months. Regional hyperthermia was administered using a 70 MHz phased array system with 4 antennas. Toxicity was scored using CTC (Common Toxicity Criteria) 3.0. The records of 18 of 20 patients could be analyzed. Median followup was 46 months. Of the 18 patients 15 (83%) completed the induction period of 6 treatments. Four patients (22%) discontinued treatment because of physical complaints without exceeding grade 2 toxicity. Toxicity scored according to CTC 3.0 was limited to grade 1 in 43% of cases and grade 2 in 14%. Mean T90 and T50 bladder temperatures were 40.6C and 41.6C, respectively. The 24-month recurrence-free survival rate was 78%. Treatment with regional hyperthermia combined with mitomycin C in patients with intermediate and high risk nonmuscle invasive bladder cancer is feasible with low toxicity and excellent bladder temperatures.

Intravesical chemotherapy for intermediate risk non-muscle invasive bladder cancer recurring after a first cycle of intravesical adjuvant therapy.

Context:The therapeutic strategy in intermediate risk (IR) non-muscle invasive bladder cancer (NMIBC) recurring after intravesical therapy (IT) is not well defined. Most patients are usually retreated by Bacillus Calmette-Guerin (BCG).Aims:To evaluate the efficacy of intravesical chemotherapy (ICH) given at recurrence after the first cycle of ICH in IR-NMIBC recurring 6 months or later.Settings and Design:Retrospective analysis of the efficacy of ICH given after previous IT.Materials and Methods:The clinical files of IR-NMIBC patients recurring later than 6 months after transurethral resection (TUR) and IT and retreated by IT were reviewed. The patients should be at intermediate risk both initially and at the first recurrence. BCG should have been given at full dose. Cytology and cystoscopy were performed 3 monthly for 2 years and then 6 monthly.Statistical Analysis:The RFS was estimated by the Kaplan-Meier method and the differences between treatment groups were compared by log-rank test. Mann Whitney U-test was used to compare the parameters’ distribution for median time to recurrence. Multivariate Cox proportional hazards models were used.Results:The study included 179 patients. The first IT was ICH in 146 (81.6%) and BCG in 33 (18.4%), re-IT was ICH in 112 (62.6%) and BCG in 67 (37.4%) patients. Median time to recurrence was 18 and 16 months after first and second IT (P = 0.32). At 3 years, 24 (35.8%) and 49 (43.8%) patients recurred after BCG and ICH, respectively (P = 0.90). No difference in RFS was found between BCG and ICH given after a first cycle of ICH (P = 0.23).Conclusions:Re-treatment with ICH could represent a legitimate option to BCG in patients harboring IR-NMIBC recurring after TUR and previous ICH. Prospective trials are needed.