Symptoms and General Pathology

All Conditions

Neoplasms

Rare Diseases

Recurrence

Carcinoma

Carcinoma, Transitional Cell

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Disease Attributes

Transitional Cell Carcinoma

Transitional Cell Cancer of the Renal Pelvis and Ureter

Antineoplastic Agents

All Drugs and Chemicals

Docetaxel

Tubulin Modulators

Antimitotic Agents

After Surgery, intravesical chemotherapy with in 48 hrs (Docetaxel 75 mg diluted in 100 cc of normal saline)

After Surgery, intravesical chemotherapy with in 48 hrs (Placebo, 100 cc of normal saline)

Intravesical Instillation of Docetaxel (Docetaxel 75 mg diluted in 100 cc of normal saline) after operation of Upper urinary tract urothelial carcinoma (With in 48 hrs)

Intravesical Instillation of Normal saline (100 cc of normal saline) after operation of Upper urinary tract urothelial carcinoma (With in 48 hrs)

Placebo Normal saline

Ja Hyeon Ku, M.D.,PH.D

Bum Sik Tae, M.D

Ja Hyeon Ku, M.D, Ph.D

The investigators evaluated the efficacy of a single early intravesical instillation of doxetaxel in the prevention of bladder recurrence after nephroureterectomy or distal ureterectomy for upper urinary tract urothelial carcinoma (UUT-UC).

Approximately 20% to 50% of patients with upper urinary tract urothelial carcinoma (UUT-UC) experience bladder recurrence after nephroureterectomy. Although many agents have been administered for the prevention of bladder recurrence, the standard prophylactic treatment has yet to be established. A meta-analysis found that a single instillation of chemotherapy immediately after transurethral resection of bladder tumor (TURBT) significantly decreased the risk of recurrence in patients with bladder cancer. Indeed, a single early instillation of Docetaxel was found to reduce the post-TURBT bladder recurrence rate among patients with bladder cancer.

In this prospective, randomized study, the investigators evaluated the efficacy of a single, early, intravesical instillation of Docetaxel in the prevention of bladder recurrence after nephroureterectomy for UUT-UC.

The Effectiveness and Safety of Intravesical Docetaxel Instillation for Prevent Bladder Recurrence

The Effectiveness and Safety of Intravesical Docetaxel Instillation After Operation to Prevent Intravesical Recurrence After Radical Nephroureterectomy or Distal Ureterectomy in Upper Urinary Tract Urothelial Carcinoma: A Prospective Study

Present of bladder recurrence after intervention in follow up cystoscopy or CT scan

Present of adverse event after intervention

Overall Survival rate during follow up period

Time to bladder recurrence after intervention in follow up cystoscopy or CT scan

Seoul National University Hospital

Professor, MD., PHD.

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Urinary Bladder Neoplasms

Non-Muscle Invasive Bladder Neoplasms

Urologic Neoplasms

Urogenital Neoplasms

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Urinary Bladder Diseases

Urologic Diseases

Male Urogenital Diseases

Anti-Infective Agents

Mitomycins

Mitomycin

Anti-Bacterial Agents

Antibiotics, Antitubercular

Alkylating Agents

Enzyme Inhibitors

Patients with non-muscle invasive bladder cancer who underwent transurethral resection alone;

Patients with non-muscle invasive bladder cancer who underwent one intravesical instillation of mitomycin-C immediately after transurethral resection

Patients with non-muscle invasive bladder cancer who underwent single immediate intravesical instillation of electromotive mitomycin-C immediately before transurethral resection

Mitomycin-C 40 mg

Savino M Di Stasi, MD, PhD

Early single instillation of chemotherapy after TUR is recommended in the European Association of Urology Guidelines. Nevertheless, the procedure is suboptimal for patients with multiple tumors, sometimes is not tolerated and it can results in severe complications. In both laboratory and clinical studies, intravesical electromotive drug administration (EMDA) increases mitomycin-C (MMC) bladder uptake, resulting in an improved clinical efficacy in non-muscle invasive bladder cancer (NMIBC). The investigators will compare the effects of one immediate pre-TUR intravesical EMDA/MMC instillation with one immediate post-TUR intravesical passive diffusion MMC (PD/MMC) instillation and TUR alone in patients with NMIBC.

All eligible patients with primary NMIBC will be randomized into 3 groups who will undergo transurethral resection alone (TUR/alone); TUR plus single immediate postoperative instillation (immediately after TUR) of 40 mg PD/MMC with a dwell time of 60 minutes; or single immediate preoperative instillation (immediately before TUR) of 40 mg EMDA/MMC with 20 mA electric current for 30 minutes. Patients with intermediate and high risk NMIBC will undergo adjuvant intravesical therapy. The primary end points will be the recurrence rate and disease-free interval. All clinical analyses will be performed on an intent to treat basis.

Preoperative Intravesical Electromotive Mitomycin-c for Primary Non-muscle Invasive Bladder Cancer

Single Preoperative Intravesical Instillation of Electromotive Mitomycin-c for Primary Non-muscle Invasive Bladder Cancer: a Prospective Randomized Trial.

University of Rome Tor Vergata

Professor

Epirubicin

will receive single intravesical dose of epirubicin intravesical therapy (50 mg) within 48 hours of radical nephroureterectomy with open bladder cuff excision.

will receive a single intravesical dose of epirubicin and an additional 6 weekly doses of intravesical therapy (50 mg) after surgery then monthly maintenance therapy for 1 year.

Immediate instillation of intravesical chemotherapy-Epirubicin-

Maintainance therapy of intravesical chemotherapy-Epirubicin-

Yasser M. Osman, MD

This clinical trial is designed to compare the effect of single postoperative intravesical chemotherapy instillation versus maintenance therapy on reducing bladder cancer recurrence after surgery for UTUC.

INTRODUCTION Upper tact urothelial carcinoma (UTUC) arises from the urothelial lining of the urinary tract from the renal calyces to the ureteral orifice. It comprises 10 % of all renal tumors and 5% of all urothelial malignancies (Jemal et al., 2007). A common feature of UTUC is multiple anatomic locations in the urinary tract either synchronous or metachronous. While synchronous bladder tumor can be identified at time of evaluation of UTUC, recurrent bladder tumor remains a major concern.

Incidence of bladder recurrence after management of UTUC varies considerably from 20% - 50% (Kirkali and Tuzel., 2003; Hall et al., 1998). Although the risk factors for development of bladder tumor post surgical management of UTUC were previously studied, considerable variations were observed in the literature. In a recent meta-analysis, Seisen et al., in 2014 have identified male gender, previous bladder cancer, and preoperative chronic kidney disease as patient-specific predictors. While tumor-specific predictors were as follows: positive preoperative urinary cytology, ureteral location, multifocality, invasive stage, and necrosis. Lastly, treatment-specific predictors were a laparoscopic approach, extravesical bladder cuff removal, and positive surgical margins.

To date, two theories have been proposed for intravesical recurrence after radical nephroureterectomy including intraluminal seeding of a single transformed cell (Habuchi et al., 1993) and pan-urothelial field defect e.g. carcinogenic exposure of the entire urothelial tract can lead to independent multifocal development (Takahashi et al., 2001; Jones et al., 2005). Therefore, it has been suggested that administration of a single dose of intravesical chemotherapy in the early postoperative period might prevent seeding of transitional cancer cells and therefore might help reduce the incidence of urothelial tumor recurrence in the first year post surgery (O'Brien et al., 2011). To the best of our knowledge, only two randomized controlled trials have investigated this hypothesis (O'Brien et al., 2011; Ito et al., 2013 ). O' Brien et al., 2011, have reported 16% of patients in the mitomycin C arm and 27% of patients in the standard treatment arm developed bladder cancer recurrence within the first year postoperative. Ito et al., 2013, reported 16.9% of patients in the pirarubicin arm and 31.8% of patients in the standard treatment arm developed bladder cancer recurrence within the first postoperative year. Based on these findings, it has been recommended in the last European association of urology guidelines that postoperative instillation of chemotherapy is recommended to avoid bladder cancer recurrence "grade B recommendation" (Roupret et al., 2013).

In 2001 Sakamoto et al., examined the significance of intravesical instillation of Mitomycin C and cytosine arabinoside over 2 years period. They showed that instillation would reduce the recurrence rate in the bladder after surgery for upper urinary tract tumors. However, this study was underpowered to detect the desired difference. The investigators hypothesized that the 16% incidence of bladder tumor recurrence after single postoperative instillation of intravesical chemotherapy after surgery for UTUC might be attributed to the influence of pan-urothelial field defect theory. Therefore, the investigators assume that maintenance intravesical chemotherapy would significantly reduce this percentage of tumor recurrence.

AIM OF THE WORK This clinical trial is designed to compare the effect of single postoperative intravesical chemotherapy instillation versus maintenance therapy on reducing bladder cancer recurrence after surgery for UTUC.

PATIENTS AND METHODS

Patients:

Type of the study A randomized controlled trial (RCT), phase II.

Study locality Urology Nephrology Center (UNC)

Study design

Patients with UTUC will be prospectively randomized into two groups using excel software by random table function:

1. Group 1: will receive single intravesical dose of epirubicin intravesical therapy (50 mg) within 48 hours of radical nephroureterectomy with open bladder cuff excision.
2. Group 2: will receive a single intravesical dose of epirubicin and an additional 6 weekly doses of intravesical therapy (50 mg) after surgery then monthly maintenance therapy for 1 year.

Exclusion criteria

1. Patients with history of bladder tumor
2. Patients with synchronous bladder tumor
3. Patients with advanced stage (T4)

Power calculation and Statistical analysis All statistical analysis will be performed using IBM v. 20 statistical software and the statistical tests will be used appropriately whenever indicated. The calculation of sample size is conducted using G\*power statistical software (Faul F et al., 2007). The recurrence rate in the control arm of the study was reported to be 16% after single intravesical dose of chemotherapy. If the expected treatment effect of maintenance chemotherapy was similar to that observed in bladder tumor, there would be a reduction in recurrence rate by 38% )Huncharek M et al., 2001). Therefore, to detect this level of difference at a power of 80% and 5% level of significance, 35 patients will be required to detect the difference between groups (1) and (2) and accounting for 15% losses in each arm, 40 patients will be randomized in each arm.

Methods:

Intervention Patients will be randomly allocated into one of the two groups using excel software by random table function at the day of surgery. Radical nephroureterectomy will be done through the open or laparoscopic approach while bladder cuff excision will be performed through the open approach. All data will be prospectively maintained and include patients' demographics, preoperative laboratory parameters, operative details and postoperative complications

Follow up The scheduled follow up will be according to the EUA guidelines (Roupret M et al., 2013) by scheduling a urine cytology and cystoscopy at 3 months then at one year while CT urography at one year for non-invasive tumors and at 6 months and one year for invasive tumors. All chemotherapy-related complications will be reported.

Outcome and end-point The primary outcome of the study is the diagnosis of intravesical recurrence within the first year after surgery. The secondary outcome is to determine the adverse events postoperative morbidity, mortality and survival of patients with UTUC.

Prophylactic Intravesical Chemotherapy After Radical Nephroureterectomy for Upper Tract Urothelial Carcinoma: a Randomized Controlled Trial Between Single Postoperative Dose Versus Maintenance Therapy.

The primary outcome of the study is the diagnosis of intravesical recurrence within the first year after surgery.

The secondary outcome is to determine the adverse events postoperative morbidity, mortality and survival of patients with UTUC.

Mansoura University

Fellow in Urology, Urology and Nephrology Center, Mansoura University, Mansoura, Egypt

Wounds and Injuries

Hyperthermia

Fever

Gemcitabine

Antimetabolites

Patients undergo Transurethral Resection of Bladder Tumors (TURBT) and receive Intravesical Chemotherapy.

Patients undergo Transurethral Resection of Bladder Tumors (TURBT) and Hyperthermic Intravesical Chemotherapy (HIVEC)

Transurethral Resection of Bladder Tumors

TURBT

Hyperthermic Intravesical Chemotherapy with Gemcitabine (3g/150ml NS) at 45 °C for 60 minutes. Induction perfusion was required to start within 4 weeks, once a week (±5 days) for 6 to 8 times. After the last induction infusion, maintenance infusion was performed, once every month (±2 weeks) for 1 year from the first induction infusion.

HIVEC

Intravesical Chemotherapy with Gemcitabine (3g/150ml NS). Induction perfusion was required to start within 4 weeks, once a week (±5 days) for 6 to 8 times. After the last induction infusion, maintenance infusion was performed, once every month (±2 weeks) for 1 year from the first induction infusion.

Intravesical Chemotherapy

Shuzhong Cui, MD

Jing Li, MD

The purpose of this study is to determine the efficacy and safety of Hyperthermic Intravesical Chemotherapy (HIVEC) with Gemcitabine (GEM) after Transurethral Resection of Bladder Tumors (TURBT) in the treatment of medium or high-risk group Non-Muscle-Invasive Bladder Cancer (NMIBC).

In this study, patients with Non-Muscle-Invasive Bladder Cancer (NMIBC) and planed to undergo Transurethral Resection of Bladder Tumors (TURBT) are randomized into HIVEC group and control group. In HIVEC group, HIVEC is performed with Gemcitabine Gemcitabine (3g/150ml NS) at 45 °C for 60 minutes within 4 weeks, once a week (±5 days) for 6 to 8 times, once a month to 1 year. For the patients in the control group, Intravesical Chemotherapy is administered after TURBT. The primary endpoint is 2-year recurrence rate. Secondary end points include 1-year recurrence rate, recurrence-free survival (RFS) rate, disease free survival (DFS) rate, time to treatment failure (TTF), Success rate of therapeutic operation, Instrument performance evaluation, quality of international prostate symptom score, quality of Urinary Symptoms Distress Score. All efficacy analyses are conducted in the intention-to-treat population. Safety analysis include only patients who receive their randomly assigned treatment.

HIVEC in Patients With Non-Muscle-Invasive Bladder Cancer

A Multicenter Prospective Randomized Controlled Clinical Trial of Hyperthermic Intravesical Chemotherapy After Transurethral Resection of Bladder Tumors in Patients With Non-Muscle-Invasive Bladder Cancer

The patients were observed for 2 years since they received HIVEC or intravesical chemotherapy，and cystoscopy was repeated every 3 months. If a new tumor-like organism is seen under the microscope, and pathology indicates urothelial carcinoma of the bladder after TURBT or cystoscopic biopsy, the tumor is considered to have recurred. 2-year recurrence rate = number of recurrence cases within 2 years / total number of enrolled cases \* 100%.

1-year recurrence rate = number of recurrence cases within 1 years / total number of enrolled cases \* 100%.

Recurrence free survival is calculated from the date of randomization to the date of record recurrence or death from any cause, whichever occurred first.

Time to treatment failure is calculated from the date of randomization to the date of treatment discontinuation/termination, including any reason for discontinuation/termination, such as disease progression, death, withdrawal due to adverse events, subject's refusal to continue the study, or use of a new treatment.

IPSS is International Prostate Symptom Score (IPSS), 0\~35, the higher the score, the worse the symptom severity is.

BS is Bother of Score (BS), 0\~6, the higher the score, the worse the performance is.BS is the Bother of Score (BS), 0\~6, the higher the score, the worse the performance is.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
The Effectiveness and Safety of Intravesical Docetaxel Instillation for Prevent Bladder Recurrence	NCT03209206	Urothelial Carc...	Docetaxel Placebo Normal ...	19 Years - 85 Years	Seoul National University Hospital
The Effectiveness and Safety of Intravesical Docetaxel Instillation for Prevent Bladder Recurrence	NCT03209206	Urothelial Carc...	Docetaxel Placebo Normal ...	19 Years - 85 Years	Seoul National University Hospital
Preoperative Intravesical Electromotive Mitomycin-c for Primary Non-muscle Invasive Bladder Cancer	NCT01149174	Superficial Bla...	Mitomycin-C 40 ...	18 Years - 90 Years	University of Rome Tor Vergata
Prophylactic Intravesical Chemotherapy After Radical Nephroureterectomy for Upper Tract Urothelial Carcinoma: a Randomized Controlled Trial Between Single Postoperative Dose Versus Maintenance Therapy.	NCT02438865	Neoplasm, Urete... Neoplasm, Bladd...	Immediate insti... Maintainance th...	-	Mansoura University
HIVEC in Patients With Non-Muscle-Invasive Bladder Cancer	NCT06327932	Non-Muscle-Inva...	TURBT HIVEC Intravesical Ch... Gemcitabine	18 Years - 80 Years	Affiliated Cancer Hospital & Institute of Guangzhou Medical University

Spots Global Cancer Trial Database for intravesical chemotherapy