Intravesical Instillation Chemotherapy Research Articles

Post-Operative Single Immediate Intravesical Instillation Chemotherapy as Prophylaxis for Reccurence after Transurethral Resection of Low Risk Non-Muscle-Invasive Bladder Cancer

We evaluated the efficacy of single-dose instillation of pirarubicine hydrochloride (THP) in the chemoprophylaxis of non-muscle-invasive bladder cancer(NMIBC). In a retrospective study, 135 evaluable patients were assigned to three groups after transurethral resection of bladder tumors (TURBT). In group 1, patients received no adjuvant therapy after TURBT. In group 2, patients received a single-dose of 30 mg THP in 30 ml normal saline immediately after TURBT. In group 3, patients received 30 mg THP in 30 ml normal saline 2 weeks after TURBT , and the instillations were repeated for 4 weeks, then every other week twice and successively monthly for 6 months. Patients were followed with cystoscopy and urine cytology every 3 months for the first 2 years and every 6 months thereafter. The 3- and 5-year non-recurrence rates were 66.9%, and 66.0%, respectively, in group 1, 85.6%, and 85.6%, respectively, in group 2, and 93.6%, and 77.9%, respectively, in group 3. There was a significant difference only between group 1 and group2 (P ＝0.048). With respect to the recurrence per month, there was a significant difference between the 3 groups (P＝0.014) for the first 2 years. However, there was no significant difference thereafter. Limitations of our study are its retrospective and nonrandomized nature with a limited number of patients.

Positively charged polypeptide nanogel enhances mucoadhesion and penetrability of 10-hydroxycamptothecin in orthotopic bladder carcinoma

Bladder cancer (BC) has become a serious public health problem due to its continuously rising incidence, high recurrence rate, and poor quality of life. Intravesical instillation of chemotherapy, one of common and important treatment strategy for BC, is restricted partially due to the short residence time and the low penetration ability of current antineoplastic agent formulations in clinic. Herein, a positively charged disulfide-core-crosslinked polypeptide nanogel of poly(l-lysine)–poly(l-phenylalanine-co-l-cystine) (PLL–P(LP-co-LC)) was synthesized. 10-Hydroxycamptothecin (HCPT) was loaded into the core via a facile diffusion to obtain loading nanogel (i.e., NG/HCPT). The reduction-responsive cationic polypeptide nanogel not only showed a high drug-loading efficiency, a prolonged residence time, and an improved tissue penetration capability, but also demonstrated an ability to accurately and rapidly release HCPT in bladder cancer cells. NG/HCPT exhibited superior cytotoxicity against human T24 bladder cancer cells compared to that of free HCPT in vitro. Moreover, the positively charged loading nanogel exhibited significantly enhanced antitumor efficacy and reduced side effects toward orthotopic bladder cancer model in vivo. Overall, the smart polypeptide nanogel with enhanced residence and permeability provides a promising drug delivery platform for local chemotherapy of BC.

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 ...

Comparison of intravesical bacillus Calmette-Guerin and mitomycin C administration for non-muscle invasive bladder cancer: A meta-analysis and systematic review.

The aim of the present meta-analysis was to compare the benefits of Bacillus Calmetter-Guerin (BCG) and mitomycin C in the treatment of patients with superficial bladder cancer. The present meta-analysis analyzed the benefits of BCG and mitomycin C in the treatment of patients with superficial bladder cancer by comparing progression-free survival (PFS) rates in patients treated with either of the drugs following transurethral resection. The Medline, Cochrane and EMBASE databases were searched between January 1966 and August 31, 2014 for studies that investigated the efficacy of the intravesical instillation of chemotherapy in patients with non-muscle invasive bladder cancer who had been treated with transurethral resection. Search terms included: ‘Urinary bladder neoplasms’, ‘superficial bladder cancer’ and ‘non-muscle invasive bladder cancer’; ‘bacillus Calmette-Guerin’ or ‘BCG’; ‘mitomycin C’; and ‘intravesical administration’. Sensitivity and data quality analyses were performed. A total of 6 randomized controlled studies were included with 1,289 patients. Complete 5-year PFS data for patients who received intravesical resection and were treated with mitomycin C or BCG was provided for 3 of the 6 studies, which were therefore included in the meta-analysis. The overall analysis revealed a significant benefit of BCG compared with mitomycin C in terms of 5-year PFS rate (odds ratio, 0.53; 95% confidence interval, 0.38–0.75; P<0.001), indicating that BCG was superior to mitomycin C therapy in patients with non-muscle invasive bladder cancer following transurethral resection.

Minimizing Staff Exposure to Antineoplastic Agents During Intravesical Therapy.

Exposure to chemotherapy is a daily risk for nurses in oncology infusion centers. Although significant advances have been made in developing systems to make IV administration of antineoplastic agents safer, less attention has been given to developing systems to minimize exposure risk during instillation of intravesical chemotherapy. This article describes the use of a closed system developed at a comprehensive cancer center and compares it to two closed systems reported in the literature. At a Glance • Safe handling of biohazard medications is important for all healthcare workers involved in the administration of antineoplastic agents. • Nurses need to advocate for use of chemotherapy administration systems that minimize exposure to staff and patients. • Infrequently performed procedures need to be supported by clearly specified procedural steps that are readily accessible to the nurse.

Intra-Arterial Chemotherapy for Muscle-Invasive Bladder Cancer Following Transurethral Resection

Purpose: To assess the efficacy of intra-arterial chemotherapy as a bladder-preservation treatment in patients with muscle-invasive bladder cancer (MIBC) following transurethral resection of bladder tumors (TURBT). Materials and Methods: From 2005 June to 2012 November, 46 patients diagnosed with MIBC (clinical stage T2-T3N0M0) underwent three courses of cisplatin-based intra-arterial chemotherapy as a remedial approach for bladder preservation after TURBT. All patients also received intravesical instillation of chemotherapy as a maintenance strategy. Results: All 46 patients completed the treatment with minor complications. The median follow-up time was 34.5 months (range, 8-87 months). Thirty-two patients (69.6%) demonstrated complete response. The three-year and five-year overall survival was 70.65 and 61.23%, and the disease-specific survival over the same periods was 78.03 and 67.62%, respectively. During the entire follow-up period, more than 80% preserved their bladder. Conclusions: Intra-arterial chemotherapy can be performed as a remedial treatment for MIBC patient following TURBT. Combined with TURBT, it offers an option for bladder preservation therapy on patients who are unable or unwilling to undergo radical cystectomy.

Long-term follow-up of TaG1 non–muscle-invasive bladder cancer

ObjectivesTo retrospectively assess the long-term outcome of patients initially diagnosed with TaG1 non–muscle-invasive bladder cancer (NMIBC) with no immediate postoperative instillation of intravesical chemotherapy and evaluate the reproducibility of the European Organization for Research and Treatment of Cancer (EORTC) scoring system for predicting bladder cancer outcome. Methods and materialsA retrospective analysis of 481 consecutive cases of initially diagnosed TaG1 NMIBC according to the 1973 World Health Organization classification between 1995 and 2008 in a single institution was performed. Time to first recurrence, time to progression to T1 or G3 bladder cancer, and time to progression to muscle-invasive bladder cancer were studied. Time to event distributions was estimated by means of cumulative incidence functions to accurately take into account the patients who died (competing risk) before recurrence or progression. The Harrell c statistic calculation was used for our study׳s data results as well the original data from EORTC to compare the predictive power of a survival model. ResultsThe median follow-up was 88 months (interquartile range: 51–135mo). The 10-year recurrence-free, T1 or G3 NMIBC progression-free, and muscle-invasive bladder cancer progression-free survival rates were 64.2%, 96.6%, and 97%, respectively. In multivariate analysis, tumor size and number of lesions were prognostic variables of the risk of recurrence. In our study and EORTC data sets, the Harrell c values obtained were c = 0.85 (95% CI: [0.75, 0.93]) and c = 0.85 (95% CI: [0.75, 0.93]), respectively. ConclusionOur study reports a detailed and extensive outcome of TaG1 NMIBC treated by TURB with no immediate postoperative intravesical instillation of chemotherapy. Our results suggest that the EORTC is a useful external validation scoring system for predicting bladder cancer outcome.

1003 Recurrence prevention by combination of photodynamic diagnosis-assisted transurethral resection of the bladder and single postoperative intravesical chemotherapy instillation in patients with nonmuscle-invasive bladder cancer

1003 Recurrence prevention by combination of photodynamic diagnosis-assisted transurethral resection of the bladder and single postoperative intravesical chemotherapy instillation in patients with nonmuscle-invasive bladder cancer

PD35-08 RISK FACTORS FOR INTRAVESICAL RECURRENCE AFTER RADICAL NEPHROURETERECTOMY FOR UPPER TRACT UROTHELIAL CARCINOMA: A META-ANALYSIS

You have accessJournal of UrologyBladder Cancer: Upper Tract Tumors I1 Apr 2014PD35-08 RISK FACTORS FOR INTRAVESICAL RECURRENCE AFTER RADICAL NEPHROURETERECTOMY FOR UPPER TRACT UROTHELIAL CARCINOMA: A META-ANALYSIS Haichao Yuan, Ping Han, and Qiang Wei Haichao YuanHaichao Yuan More articles by this author , Ping HanPing Han More articles by this author , and Qiang WeiQiang Wei More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2014.02.2421AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES The standard management for upper tract urothelial carcinoma (UTUC) is radical nephroureterectomy (RNU) with bladder cuff excision, but after surgery, approximately 22% to 47% of patients with UTUC develop subsequent intravesical recurrence (IVR), and recurrence in the contralateral upper tract is observed in 26% of patients. Considering this high incidence of IVR after RNU, several risk factors were reported as predictive for IVR after RNU. Until recently, most of the risk factors were still under debate. The aim of our study is to conduct a meta-analysis based on the recent literature to explore the risk factors for IVR after RNU for UTUC. METHODS An electronic search of the Medline, Embase, Cochrane Library, CancerLit and ClinicalTrials.gov databases was performed to identify relevant studies published prior to May 2013. The studies were included if they reported risk factors related to bladder or intravesical recurrence after RNU for UTUC. Studies were excluded from the analysis if they were case reports, meeting abstracts or conference proceedings. The studies which included neoadjuvant or adjuvant chemotherapy or intravesical instillation chemotherapy after RNU were excluded. RESULTS Forty studies, with 12,010 patients, were included in our meta-analysis. Our study indicated that a statistically significant difference in IVR after RNU was found in the male vs. female (OR: 0.72; 95%CI: 0.59 to 0.85), ureteral vs. renal pelvis (OR: 1.18; 95%CI: 1.00 to 1.36), T2-4 vs. Tis and Ta,1 (OR: 0.53; 95%CI: 0.40 to 0.66), larger vs. smaller tumor size (OR: 1.02; 95%CI: 1.01 to 1.03) and previous/synchronous bladder cancer vs. the absence of bladder cancer (OR: 1.59; 95%CI: 1.26 to 1.9). No significant differences in IVR after RNU were found in the high vs. low age, multifocal tumors vs. single tumor, G3 vs. G1,2, high vs. low grade, N0 vs. N+, concomitant carcinoma in situ (CIS) vs. the absence of CIS, positive vs. negative lymphovascular invasion, open versus laparoscopic nephroureterectomy and endoscopic vs. transvesical technique. CONCLUSIONS our study showed that female patient, ureteral tumor, larger tumor, low T stage (Tis, a, 1) and the history of bladder cancer were significant risk factors related to IVR after nephroureterectomy. The age, tumor multifocality, G grade, lymph node status, lymphovascular invasion, Concomitant CIS, type of surgery and management of the bladder cuff were not significantly associated with the risk of IVR after nephroureterectomy. © 2014FiguresReferencesRelatedDetails Volume 191Issue 4SApril 2014Page: e893-e894 Advertisement Copyright & Permissions© 2014MetricsAuthor Information Haichao Yuan More articles by this author Ping Han More articles by this author Qiang Wei More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Are EORTC risk tables suitable for Chinese patients with non-muscle-invasive bladder cancer?

ObjectiveTo evaluate the applicability of using EORTC risk tables in Chinese patients with non-muscle-invasive bladder cancer. Material and methodsBetween October 2000 and July 2009, 301 patients with NMIBC who underwent transurethral resection of the bladder tumor (TURBT) at our hospital were followed up. The probability of recurrence and progression at 1 year and 5 years post-operatively was calculated along with the 95% confidence intervals. We then compared the actual probabilities in our center to those obtained through the application of the EORTC risk tables. ResultsMedian patient age was 67 years (range, 21–92 years), and the median follow-up duration was 46 months (range, 2–151 months). The probability of recurrence at 1 year ranged from 2% to 58%, and the probability of progression ranged from less than 1.2% to 30%. At 5 years, the probability of recurrence ranged from 12% to 85%, and the probability of progression ranged from less than 2.9% to 50%. An overlapping of the confidence intervals of the probability between our series and the EORTC group is detected. ConclusionsAlthough the immediate instillation of intravesical chemotherapy may reduce the risk of recurrence, EORTC risk tables could predict recurrence and progression in Chinese patients with non-muscle-invasive bladder cancer.

Predictive Value of Clinicopathological Markers for the Metachronous Bladder Cancer and Prognosis of Upper Tract Urothelial Carcinoma

Upper tract urothelial carcinoma (UTUC) is rare but aggressive with poor prognosis. We aimed to find effective predictive markers for recurrence and prognosis in UTUC patients. In this retrospective study, we included 88 UTUC patients treated with radical neprhoureterectomy (RNU) and analyzed their clinicopathological parameters. For study of incidence of metachronous bladder tumor, models were adjusted with inclusion of prophylactic intravesical instillation chemotherapy. The mean follow-up was 28.59 months (2 to 82 mo). Lack of gross hematuria (RR 0.060, 95%CI 0.008–0.468), tumor located at ureter (RR 0.037, 95%CI 0.004–0.378), advanced stage and higher p53 expression were independent factors for worse survival. Recurrence of bladder cancer occurred 20% of patients at median follow-up of 37.65 months (5 to 82 mo). Higher tumor grade (RR 5.998, 95%CI 1.359–26.479) and presence of ipsilateral non-functioning kidney at diagnosis (RR 5.982, 95%CI 1.338–26.750) were predictors for recurrence. The present study identified several parameters with predictive value in the prognosis and intravesicle recurrence in UTUCand shed light on the better monitoring and management of the disease.

Clinical Trial Design for the Development of New Therapies for Nonmuscle-invasive Bladder Cancer: Report of a Food and Drug Administration and American Urological Association Public Workshop

To summarize the discussion at a public workshop, cosponsored by the U.S. Food and Drug Administration (FDA) and the American Urological Association, reviewing potential trial designs for the development of new therapies for non-muscle-invasive bladder cancer (NMIBC). There have been only 3 drug approvals for NMIBC in the last 30 years, and product development for this disease has been stymied by difficulties in trial design and patient accrual. A workshop evaluating potential trial design for the development of therapies for NMIBC was held in San Diego, CA, in May 2013. Invited experts representing all stakeholders, including urology, medical oncology, radiation oncology, industry, and patient advocates, discussed development of products for all risk strata of NMIBC. The panel responded to specific questions from the FDA, discussing eligibility criteria, efficacy endpoints, and trial design for patients with a mix of high-grade papillary disease and carcinoma in situ, Bacillus Calmette-Guerin (BCG)-refractory disease, and intermediate-risk disease. Panel members also addressed the magnitude of response that would be clinically meaningful for various disease strata and trial design options for perioperative intravesical chemotherapy instillation at the time of resection of bladder tumors. Expert commentary provided by panel members will inform a planned FDA guidance on pathways for drug and biologic development for NMIBC and will be discussed at meetings of the FDA's Oncologic Drugs Advisory Committee. FDA intends to develop a set of principles that can be used to promote the development of new products for this disease.

The use of immediate postoperative instillations of intravesical chemotherapy after TURBT of NMIBC among European countries

The aim of this study was to assess the use of immediate postoperative instillation of intravesical chemotherapy (IPOIC) after transurethral resection of bladder tumour (TURBT) of nonmuscle invasive bladder cancer (NMIBC) in Europe. Urologists based in five European Union nations were asked to extract information from the records of patients with NMIBC-urothelial carcinoma who received at least one TURBT. Multivariate logistic regression models were developed to determine the significant predictors of IPOIC usage. Data were weighted to control for country-to-country and other differences. Overall, 324 urologists (58 France, 72 Germany, 62 Italy, 65 Spain, 67 United Kingdom) were involved; the participation rate was 55 %. Overall, 771 patients received 954 TURBTs (mean-1.2/patient), of which 413 of the TURBTs (43.3 %) were administered IPOIC . Sixty-six of the 413 IPOICs (16.0 %) were for a recurrent tumour. Five of the tested variables were significantly associated with a patient's likelihood of receiving IPOIC after TURBT. Variables in the order of significance are as follows: (1) country (United Kingdom, patients most likely to receive IPOIC; France, least likely); (2) progression risk (physician assessed) [lower-risk conditions (no CIS, tumour < 3 cm) or intermediate risk-more likely]; (3) whether urologist completed a uro-oncology fellowship (completed-more likely); (4) recurrence risk (physician assessed) [higher-risk conditions (≥T2, ≥3 cm, CIS)-more likely]; and (5) physician's NMIBC patients volume (higher volume-more likely). This study revealed wide practice variation and substantial noncompliance with European Association of Urology Guidelines on the use of IPOIC after TURBT for NMIBC.

Practice Based Collaboration to Improve the Use of Immediate Intravesical Therapy after Resection of Nonmuscle Invasive Bladder Cancer

Perioperative instillation of intravesical chemotherapy after bladder tumor resection is supported by level I evidence showing a 30% decrease in tumor recurrence. However, studies of administrative data sets show poor use in practice. We prospectively evaluated the use of perioperative intravesical chemotherapy in a multipractice quality improvement collaborative. Cases were categorized as ideal for intravesical chemotherapy (1 or 2 papillary tumors, cTa/cT1 and completely resected) and nonideal. The reasons for not administering intravesical chemotherapy in ideal cases were classified as appropriate or modifiable. Before and after comparative feedback and educational interventions we calculated judicious use of intravesical chemotherapy (nonuse in nonideal cases plus use in ideal cases plus appropriate nonuse in ideal cases) and quality improvement potential (use in nonideal cases plus nonuse in ideal cases attributable to modifiable factors). We accrued a total of 2,794 cases at the 5 sites in 22 months. The rate of use in ideal cases was 38% before and 34.8% after intervention (p=0.36), while use in nonideal cases decreased from 15% to 12% (p=0.08). Overall, intravesical chemotherapy was used judiciously in 83.0% to 85.7% of cases, while the remaining 14.3% to 17.0% represented quality improvement potential. Judicious use of perioperative intravesical chemotherapy is relatively high in routine practice. Most instances of nonuse represent appropriate clinical judgment. Utilization did not change after quality improvement interventions, suggesting that there may a ceiling effect that makes it difficult to improve care that is high quality at baseline. Moreover, decreasing unnecessary use of an intervention may be easier than encouraging appropriate use of potentially toxic therapy.

Single or two instillations of pirarubicin as prophylaxis for recurrence after transurethral resection of Ta and T1 transitional cell bladder cancer: A prospective, randomized controlled study.

LBA266 Background: Although single intravesical instillation chemotherapy immediately after transurethral resection (TUR) is the standard treatment for non-muscle-invasive bladder tumors, 40% to 80% of tumors show intravesical recurrence. In this prospective randomized controlled study, we try to evaluate the prophylactic efficacy and safety of twice intravesical instillation using pirarubicin (THP) administered immediately after TUR and on the next day following TUR by comparison with single instillation immediately after TUR. Methods: Between 2005 and 2009, 250 patients with Ta and T1 solitary bladder carcinoma were enrolled in this study. Patients were randomized into two groups. Group A patients were treated with two intravesical instillations of THP 30 mg/50 ml saline immediately after TUR and within 24 hours. Group B patients were treated with single instillation of the same dose immediately after TUR as a control group. The primary endpoint was duration to the first recurrence, and the secondary endpoint was safety. Results: The enrollment was closed on 2009, and the follow-up phase is in process. Of the 250 patients, 125 in Group A and 125 in Group B could be evaluated as full analysis set. One hundred eight male and 17 female were in Group A, on the other hands, one hundred five male and 20 female were in Group B. Eighty-six cases (69%) in group A, and 88 cases (70%) in group B were primary tumor. Fifty-seven cases (46%) in group A, and 56 cases (45%) in group B were small tumor (less than 10mm). There was no difference between backgrounds of both groups. The randomization worked well. In this ad interim report, median follow up was 48 months. Two-year recurrence-free rates were 76.8% in group A and 67.5% in group B. Adverse reactions related to instillation were observed in about 20% of the patients. These toxicities were mild and transient. Only the incidence of frequency in group A was higher than that in group B (20% vs. 8%, p=0.0106). Conclusions: Intravesical instillation of THP 30 mg twice within 24 hours after TUR was effective as prophylactic therapy for non-muscle-invasive cancer with tolerable toxicity problems.

Electromotive instillation of mitomycin immediately before transurethral resection for patients with primary urothelial non-muscle invasive bladder cancer: a randomised controlled trial

The clinical effect of intravesical instillation of chemotherapy immediately after transurethral resection of bladder tumours (TURBT) has recently been questioned, despite its recommendation in guidelines. Our aim was to compare TURBT alone with immediate post-TURBT intravesical passive diffusion (PD) of mitomycin and immediate pre-TURBT intravesical electromotive drug administration (EMDA) of mitomycin in non-muscle invasive bladder cancer. We did a multicentre, randomised, parallel-group study in patients with primary non-muscle invasive bladder cancer in three centres in Italy between Jan 1, 1994, and Dec 31, 2003. Patients were randomly assigned to receive treatment by means of stratified blocked randomisation across six strata. Patients and physicians giving the interventions were aware of assignment, but it was masked from outcome assessors and data analysts. Patients were randomly assigned to receive TURBT alone, immediate post-TURBT instillation of 40 mg PD mitomycin dissolved in 50 mL sterile water infused over 60 min, or immediate pre-TURBT instillation of 40 mg EMDA mitomycin dissolved in 100 mL sterile water with intravesical 20 mA pulsed electric current for 30 min. Our primary endpoints were recurrence rate and disease-free interval. Analyses were done by intention to treat. Follow-up for our trial is complete. This study is registered with ClinicalTrials.gov, number NCT01149174. 124 patients were randomly assigned to receive TURBT alone, 126 to receive immediate post-TURBT PD mitomycin, and 124 to receive immediate pre-TURBT EMDA mitomycin. 22 patients were excluded from our analyses because they did meet our eligibility criteria after TURBT: 11 had stage pT2 disease and 11 had carcinoma in situ. Median follow-up was 86 months (IQR 57-125). Patients assigned to receive EMDA mitomycin before TURBT had a lower rate of recurrence (44 [38%] of 117) than those assigned to receive PD mitomycin after TURBT (70 [59%] of 119) and TURBT alone (74 [64%] of 116; log-rank p<0·0001). Patients assigned to receive EMDA mitomycin before TURBT also had a higher disease-free interval (52 months, IQR 32-184) than those assigned to receive PD mitomycin after TURBT (16 months, 12-168) and TURBT alone (12 months, 12-37; log-rank p<0·0001). We recorded persistent bladder symptoms after TURBT in 18 (16%) of 116 patients in the TURBT-alone group (duration 3-7 days), 37 (31%) of 119 in the PD mitomycin post-TURBT group (duration 20-30 days), and 24 (21%) of 117 in the EMDA mitomycin pre-TURBT group (duration 7-12 days); haematuria after TURBT in eight (7%) of 116 patients in the TURBT-alone group, 16 (13%) of 119 in the PD mitomycin post-TURBT group, and 11 (9%) of 117 in the EMDA mitomycin pre-TURBT group; and bladder perforation after TURBT in five (4%) of 116 patients in the TURBT-alone group, nine (8%) of 119 in the PD mitomycin post-TURBT group, and seven (6%) of 117 in the EMDA mitomycin pre-TURBT group. Intravesical EMDA mitomycin before TURBT is feasible and safe; moreover, it reduces recurrence rates and enhances the disease-free interval compared with intravesical PD mitomycin after TURBT and TURBT alone. None.

Use of cytokeratin 18 and EAU score to predict tumor recurrence in patients with non-muscle-invasive bladder cancer following single postoperative immediate intravesical chemotherapy instillation.

269 Background: We examined the prognostic factors for recurrence after TURBT using molecular markers as well as the scoring system of the EAU. Methods: Eighty-eight patients with primary or recurrent bladder tumors who underwent TURBT followed by the single postoperative immediate instillation of pirarubicin and no further instillations were enrolled between 2003 and 2006; the median follow-up period was 46 months. The time to first recurrence was the primary end point of this study. Patients were divided into EAU recurrence risk groups as follows: low-risk group (total score, 0), intermediate-risk group (total score, 1-9) and high-risk group (total score, 9-17). The intermediate-risk group patients were subdivided into a total score of 1-4 and a total score of 5-9. Immunostaining using Ki-67, pHH3, CK18 and Survivin were performed on the TURBT specimens. Results: According to the risk stratification, 5, 82, and 1 were assigned to the low-, intermediate-, and high-risk recurrence groups, respectively. During the follow-up, recurrences were observed in 0% of the low-risk group, 45% (37 out of 82) in the intermediate-risk group and 100% in the high-risk group. We evaluated various predictors of a recurrence-free outcome among the 82 intermediate-risk patients. In univariate analyses, EAU score (1-4, 32.1% vs 5-9, 62.1%; p = 0.0011), high CK18 expression (negative, 31.4% vs positive 88.8%; p &lt; 0.0001), high Ki-67 index (&lt; 5%, 35.4% vs &gt; 5%, 52.5%; p = 0.017) and high Survivin nuclear staining (&lt; 5%, 35.9% vs &gt; 5%, 62.5%; p = 0.004) were associated with recurrence. In a multivariate analysis, EAU score (HR 2.95, p = 0.003) and a high CK18 immunostaining (HR 6.70, p &lt; 0.0001) were independent predictors of disease recurrence. Conclusions: A single immediate chemotherapy instillation is, by itself, insufficient for the treatment of patients in the intermediate- or high-risk recurrence groups defined by the EAU guidelines. Strong immunohistochemical expression of CK18 and the EAU scoring system appeared to be independent predictors of clinical outcome among patients with urothelial carcinoma of the bladder. No significant financial relationships to disclose.

Impact of Routine Second Transurethral Resection on the Long-Term Outcome of Patients with Newly Diagnosed pT1 Urothelial Carcinoma with Respect to Recurrence, Progression Rate, and Disease-Specific Survival: A Prospective Randomised Clinical Trial

BackgroundTransurethral resection (TUR) of bladder tumours is not only mandatory for adequate staging but also crucial in delaying or preventing tumour recurrence and progression. ObjectiveTo evaluate the impact of routine second TUR on the long-term outcome of patients with newly diagnosed pT1 urothelial carcinoma. Design, setting, and participantsTwo hundred ten newly diagnosed T1 bladder cancer patients were prospectively randomised to two groups between January 2001 and January 2005. Second TUR was performed within 2–6 wk after the initial resection for the patients of group 1. Second TUR was not done in group 2. All patients (groups 1 and 2) received the first instillation of intravesical chemotherapy within 24h after the initial resection. Urine cytology and follow-up cystoscopy were performed at 3-mo intervals for the first year, biannually for the second year, and annually thereafter. All patients were followed until death or a minimum of 54 mo. MeasurementsThis study recorded recurrence, progression rate, and disease-specific survival. Results and limitationsThe mean follow-up period was 66.1 mo without a significant difference between the groups. Residual tumour was detected histopathologically in 35 of 105 patients in group 1. Of these patients, eight had upper-stage (pT2) disease. Recurrence was observed in 37 of the 93 patients in group 1 and 70 of the 98 patients in group 2. Median recurrence-free survival was 47 mo for group 1 compared with 12 mo for group 2. Progression was observed in 6.5% of patients for group 1 compared to 23.5% of patients for group 2 (p=0.001). Median progress-free survival was 73 mo for group 1 compared to 53.5 mo for group 2. The overall survival rate was 67.7% and 64.3% in groups 1 and 2, respectively (log-rank test result: 0.363). Only 5 of the 30 patients in group 1 died of cancer compared to 11 of the 35 patients in group 2 (p=0.038). ConclusionsWe have clearly shown that second TUR, which is performed only after complete first TUR, has significantly decreased the recurrence and progression rates in patients with newly diagnosed T1 disease compared to patients with T1 disease but with no second TUR. This study once more underscores the effect of TUR, which is usually underappreciated.

Treatment of nonmuscle invading bladder cancer: Do physicians in the United States practice evidence based medicine?

Phase 3 clinical trials performed primarily outside the US demonstrate that intravesical instillation of chemotherapy immediately after transurethral resection of the bladder (TURB) decreases cancer recurrence rates. The authors sought to determine whether US urologists have adopted this practice, and its potential effect on costs of bladder cancer (BC) care. By using 1997-2004 MEDSTAT claims data, the authors identified patients with newly diagnosed BC who underwent cystoscopic biopsy or TURB, and those who received intravesical chemotherapy within 1 day after TURB. Economic consequences of this treatment compared with TURB alone were modeled using published efficacy estimates and Medicare reimbursements. The authors used a time horizon of 3 years and assumed that this treatment was given for all newly diagnosed low-risk BC patients. Between 1997 and 2004, the authors identified 16,748 patients with newly diagnosed BC, of whom 14,677 underwent cystoscopic biopsy or TURB. Of these, only 49 (0.33%) received same-day intravesical instillation of chemotherapy. From 1997 through 2004, there has been little change in the use of this treatment. The authors estimated a 3-year savings of $538 to $690 (10% to 12%) per patient treated with TURB and immediate intravesical chemotherapy compared with TURB alone, reflecting a yearly national savings of $19.8 to $24.8 million. Instillation of intravesical chemotherapy immediately after TURB has not been embraced in the US. Adopting this policy would significantly lower the cost of BC care.

Efecto terapéutico de Mitomicina C en el postoperatorio inmediato de pacientes con tumores vesicales no músculo invasores de riesgo intermedio

IntroductionApproximately 70-85% of transitional bladder cell carcinomas are non-muscle-invasive. After an initial surgery, around 60-90% will have a recurrence, being the highest risk period the first two years. Urothelium instability could be the main reason for recurrence in mid grade tumours, reason why a single dose of a chemotherapy after transurethral resection of the bladder (TURB) might be insufficient. That is why a deferred therapy in occasions associated with maintenance is recommended. Patients and methodsA prospective, controlled and randomized study was performed. We included non-muscle-invasive mid risk bladder tumours. All patients had initially a TURB performed and were randomized to receive a single dose of mitomycin C (MMC), in the immediate postoperative period. ResultsA total of 105 patients were included. Mean follow-up was 22, 70±8, 15 months. MMC was administered to 53 patients. Of these 66, 0% had no recurrence and 34,0% had a non-muscle-invasive recurrence. Of the 52 patients in the non MMC group, 53,8% had no recurrence and 44,2% had a non-muscle-invasive recurrence and only 1 patient had a muscleinvasive progression. We did not find significantly differences in time to recurrence in mid risk tumours when using immediate postoperative single dose of MMC or deferred therapy. There was only one case of myelosuppression. DiscussionIn mid risk non-muscle-invasive tumors, some studies suggest that early intravesical instillation of chemotherapy reduces the risk of recurrence after TURB. We could not show significantly differences when comparing postoperatorive MMC versus traditional deferred instillations.