Emerging Approaches to Diagnosis and Treatment of Non-Muscle-Invasive Bladder Cancer [Entered Retrospectively]

Project Summary Title and Description

Title
Emerging Approaches to Diagnosis and Treatment of Non-Muscle-Invasive Bladder Cancer [Entered Retrospectively]
Description
Objectives. Non-muscle-invasive bladder cancer (NMIBC) frequently recurs and can progress to muscle-invasive disease. This report reviews the current evidence on emerging approaches to diagnosing and treating bladder cancer. Data Sources. Electronic databases (Ovid MEDLINE, January 1990 – October 2014; Cochrane Central Register of Controlled Trials, through September 2014; Cochrane Database of Systematic Reviews, through September 2014; Health Technology Assessment, through 3rd Quarter, 2014; National Health Sciences Economic Evaluation Database, through 3rd Quarter, 2014; and Database of Abstracts of Reviews of Effects, through 3rd Quarter, 2014), references lists, and clinical trials registries. Review Methods. Using predefined criteria, we selected studies on diagnostic accuracy of urinary biomarkers versus cystoscopy, and trials of fluorescent cystoscopy, intravesical therapy, and radiation therapy for NMIBC that evaluated bladder cancer recurrence, progression, mortality, or harms. The quality of included studies was assessed, data were extracted, and results were summarized qualitatively and using meta-analysis. Results. Urinary biomarkers were associated with sensitivity for bladder cancer that ranged from 0.57 to 0.82 and specificity from 0.74 to 0.88, for positive likelihood ratios from 2.52 to 5.53 and negative likelihood ratios from 0.21 to 0.48 (strength of evidence [SOE]: moderate for quantitative nuclear matrix protein 22 [NMP22], qualitative bladder tumor antigen [BTA], fluorescent in situ hybridization [FISH], and ImmunoCyt; low for other biomarkers). Sensitivity increased for higher stage and grade tumors. Studies that directly compared the accuracy of quantitative NMP22 and qualitative BTA found no differences in diagnostic accuracy (SOE: moderate). Most trials found fluorescent cystoscopy associated with decreased risk of subsequent bladder recurrence versus white light cystoscopy, but results were inconsistent, and there was no difference in risk of progression or mortality (SOE: low). Intravesical therapy was more effective than no intravesical therapy for reducing risk of bladder cancer recurrence (for bacillus Calmette-Guérin [BCG], RR 0.56, 95% CI 0.43 to 0.71, SOE: moderate; for mitomycin C [MMC], doxorubicin, and epirubicin, RR 0.66 to 0.72, SOE: moderate). BCG was also associated with decreased risk of bladder cancer progression, but no intravesical agent was associated with decreased risk of all-cause or bladder-cancer specific mortality. Intravesical therapy appeared to be effective across subgroups defined by tumor stage, grade, multiplicity, recurrence status, and size (SOE: low). Evidence was too limited to draw strong conclusions regarding effects of dose or duration of therapy on effectiveness. Compared with no intravesical therapy, BCG was associated with a higher rate of local and systemic adverse events (granulomatous cystitis or irritative symptoms in 27% to 84% of patients, macroscopic hematuria in 21% to 72%, and fever in 27% to 44%) (SOE: low). Compared with MMC, BCG was also associated with an increased risk of local adverse events and fever (SOE: low). One randomized trial found no difference between radiation therapy and no radiation therapy in clinical outcomes in patients with T1G3 cancers. Conclusions. Urinary biomarkers miss a substantial proportion of patients with bladder cancer, and additional research is needed to clarify advantages of fluorescent cystoscopy over white light cystoscopy. Intravesical therapy reduces risk of bladder cancer recurrence versus no intravesical therapy. BCG is the only intravesical therapy shown to be associated with decreased risk of bladder cancer progression, but is associated with a high rate of adverse events. More research is needed to define optimal doses and regimens of intravesical therapy.
Attribution
N/A
Authors of Report
N/A
Methodology description
Review Methods. Using predefined criteria, we selected studies on diagnostic accuracy of urinary biomarkers versus cystoscopy, and trials of fluorescent cystoscopy, intravesical therapy, and radiation therapy for NMIBC that evaluated bladder cancer recurrence, progression, mortality, or harms. The quality of included studies was assessed, data were extracted, and results were summarized qualitatively and using meta-analysis.
PROSPERO
CRD42014013284
DOI
10.7301/Z0R49NQZ
Notes
N/A
Funding Source
Prepared by the Pacific Northwest Evidence-based Practice Center under Contract No. 290-2012-00014-I. Rockville, MD: Agency for Healthcare Research and Quality. www.effectivehealthcare.ahrq.gov/reports/final.cfm

Key Questions

1. Key Question 1. What is the diagnostic accuracy of various urinary biomarkers compared with other urinary biomarkers or standard diagnostic methods (cystoscopy, cytology, and imaging) in 1) people with signs or symptoms warranting evaluation for possible bladder cancer or 2) people undergoing surveillance for previously treated bladder cancer? Key Question 1a. Does the diagnostic accuracy differ according to patient characteristics (e.g., age, sex, ethnicity), or according to the nature of the presenting signs or symptoms?
2. Key Question 2. For patients with non-muscle-invasive bladder cancer, does the use of a formal risk-adapted assessment approach to treatment decisions (e.g., Guidelines of the European Association of Urology or based on urinary biomarker tests) decrease mortality or improve other outcomes (e.g., recurrence, progression, need for cystectomy, quality of life) compared with treatment not guided by a formal assessed risk-adapted approach?
3. Key Question 3. For patients with non-muscle-invasive bladder cancer treated with transurethral resection of bladder tumor (TURBT), what is the effectiveness of various intravesical chemotherapeutic or immunotherapeutic agents for decreasing mortality or improving other outcomes (e.g., recurrence, progression, need for cystectomy, quality of life) compared with TURBT alone? Key Question 3a. What is the comparative effectiveness of various chemotherapeutic or immunotherapeutic agents, as monotherapy or in combination? Key Question 3b. Does the comparative effectiveness differ according to tumor characteristics, such as stage, grade, size, multiplicity, whether the tumor is primary or recurrent, or molecular/genetic markers? Key Question 3c. Does the comparative effectiveness differ according to patient characteristics, such as age, sex, ethnicity, performance status, or medical comorbidities? Key Question 3d. Does the comparative effectiveness of various chemotherapeutic or immunotherapeutic agents differ according to dosing frequency, duration of treatment, and/or the timing of administration relative to TURBT?
4. Key Question 4. For patients with high risk non-muscle-invasive bladder cancer treated with TURBT, what is the effectiveness of external beam radiation therapy (either alone or with systemic chemotherapy/ immunotherapy) for decreasing mortality or improving other outcomes compared with intravesical chemotherapy/immunotherapy alone or cystectomy?
5. Key Question 5. In surveillance of patients treated for non-muscle-invasive bladder cancer, what is the effectiveness of various urinary biomarkers to decrease mortality or improve other outcomes compared with other urinary biomarkers or standard diagnostic methods (cystoscopy, cytology, and imaging)? Key Question 5a. Does the comparative effectiveness differ according to tumor characteristics, such as histology, stage, grade, size, or molecular/ genetic markers? Key Question 5b. Does the comparative effectiveness differ according to the treatment used (i.e., specific chemotherapeutic or immunotherapeutic agents and/or TURBT)? Key Question 5c. Does the comparative effectiveness differ according to the length of surveillance intervals? Key Question 5d. Does the comparative effectiveness differ according to patient characteristics, such as age, sex, or ethnicity?
6. Key Question 6. For initial diagnosis or surveillance of patients treated for non-muscle-invasive bladder cancer, what is the effectiveness of blue light or other methods of augmented cystoscopy compared with standard cystoscopy for recurrence rates, progression of bladder cancer, mortality, or other clinical outcomes?
7. Key Question 7. What are the comparative adverse effects of various tests for diagnosis and post-treatment surveillance of bladder cancer, including urinary biomarkers, cytology, and cystoscopy?
8. Key Question 8. What are the comparative adverse effects of various treatments for non-muscle-invasive bladder cancer, including intravesical chemotherapeutic or immunotherapeutic agents and TURBT? Key Question 8a. How do adverse effects of treatment vary by patient characteristics, such as age, sex, ethnicity, performance status, or medical comorbidities such as chronic kidney disease?

Associated Extraction Forms

Associated Studies (each link opens a new tab)

TitleAuthorsYear
Multicolor fluorescence in situ hybridization (M-FISH) on cells from urine for the detection of bladder cancer.2006
Combinations of urine-based tumour markers in bladder cancer surveillance.2009
ImmunoCyt a useful method in the follow-up protocol for patients with urinary bladder carcinoma.2001
Urinary BTA-stat, BTA-trak and NMP22 in surveillance after TUR of recurrent superficial transitional cell carcinoma of the bladder.2000
Comparison of the BTA stat test with voided urine cytology and bladder wash cytology in the diagnosis and monitoring of bladder cancer.1999
Comparison of the ImmunoCyt test and urinary cytology with other urine tests in the detection and surveillance of bladder cancer.2004
Immunocytology is a strong predictor of bladder cancer presence in patients with painless hematuria: a multicentre study.2012
Improved detection of urothelial carcinomas with fluorescence immunocytochemistry (uCyt+ assay) and urinary cytology: results of a French Prospective Multicenter Study.2003
Immunocytology in the assessment of patients with painless gross haematuria.2008
Immunocytology in the assessment of patients with asymptomatic microhaematuria.
Comparison of ImmunoCyt, UroVysion, and urine cytology in detection of recurrent urothelial carcinoma: a "split-sample" study.2009
ImmunoCyt/uCyt+ improves the sensitivity of urine cytology in patients followed for urothelial carcinoma.2005
Diagnostic efficacy of the ImmunoCyt test to detect superficial bladder cancer recurrence.2001
Can urine bound diagnostic tests replace cystoscopy in the management of bladder cancer?1998
A comparison of BTA stat, hemoglobin dipstick, telomerase and Vysis UroVysion assays for the detection of urothelial carcinoma in urine.2002
Clinical utility of a multiprobe FISH assay in voided urine specimens for the detection of bladder cancer and its recurrences, compared with urinary cytology.2002
Clinical evaluation of a multi-target fluorescent in situ hybridization assay for detection of bladder cancer.2002
Results of Bard BTA test in monitoring patients with a history of transitional cell cancer of the bladder.1997
Comparison of the Bard BTA test with voided urine and bladder wash cytology in the diagnosis and management of cancer of the bladder.1997
Bard BTA test compared with voided urine cytology in the diagnosis of recurrent bladder cancer.1997
Urinary NMP22 for the detection of recurrence after transurethral resection of transitional cell carcinoma of the bladder: experience on 137 patients.1998
Urinary NMP22 and karyometry in the diagnosis and follow-up of patients with superficial bladder cancer.1998
BTA stat and BTA TRAK: A comparative evaluation of urine testing for the diagnosis of transitional cell carcinoma of the bladder.1999
Comparison of two qualitative assays, the UBC rapid test and the BTA stat test, in the diagnosis of urothelial cell carcinoma of the bladder.2000
Immunocyt: a new tool for detecting transitional cell cancer of the urinary tract.
Noninvasive detection of bladder cancer with the BTA stat test.1999
The Bard BTA test: its mode of action, sensitivity and specificity, compared to cytology of voided urine, in the diagnosis of superficial bladder cancer.1998
Exclusion criteria enhance the specificity and positive predictive value of NMP22 and BTA stat.1999
The use of the bladder-tumour associated analyte test to determine the type of cystoscopy in the follow-up of patients with bladder cancer. The United Kingdom and Eire Bladder Tumour Antigen Study Group.1997
Bladder wash cytology, quantitative cytology, and the qualitative BTA test in patients with superficial bladder cancer.1998
A study comparing various noninvasive methods of detecting bladder cancer in urine.2002
Surveillance for recurrent bladder cancer using a point-of-care proteomic assay.2006
The UroVysion fluorescence in situ hybridization assay is an effective tool for monitoring recurrence of bladder cancer.-- Not Found --
NMP22: a sensitive, cost-effective test in patients at risk for bladder cancer.-- Not Found --
Detection of bladder cancer using a point-of-care proteomic assay.2005
The value of the UroVysion assay for surveillance of non-muscle-invasive bladder cancer.2008
Nuclear matrix protein 22 as adjunct to urine cytology and cystoscopy in follow-up of superficial TCC of urinary bladder.2009
Performance of urine test in patients monitored for recurrence of bladder cancer: a multicenter study in the United States.
Variability in the performance of nuclear matrix protein 22 for the detection of bladder cancer.2006
Evaluation of the clinical value of urinary NMP22 as a marker in the screening and surveillance of transitional cell carcinoma of the urinary bladder.2001
Accuracy of the ImmunoCyt assay in the diagnosis of transitional cell carcinoma of the urinary bladder.-- Not Found --
Clinical use of urinary markers for the detection and prognosis of bladder carcinoma: a comparison of immunocytology with monoclonal antibodies against Lewis X and 486p3/12 with the BTA STAT and NMP22 tests.
Comparative evaluation of the diagnostic performance of the BTA stat test, NMP22 and urinary bladder cancer antigen for primary and recurrent bladder tumors.
BTA TRAK urine test increases the efficacy of cytology in the diagnosis of low-grade transitional cell carcinoma of the bladder.-- Not Found --
NMP 22, BTA stat test and cytology in the diagnosis of bladder cancer: a comparative study.2001
Role of uCyt+ in the detection and surveillance of urothelial carcinoma.2003
Utility of the BTA stat test kit for bladder cancer screening.1999
Screening and monitoring for bladder cancer: refining the use of NMP22.2001
The role of BTA stat in clinical practice.2002
Routine follow-up cystoscopy in detection of recurrence in patients being monitored for bladder cancer.2001
Comparative predictive values of urinary cytology, urinary bladder cancer antigen, CYFRA 21-1 and NMP22 for evaluating symptomatic patients at risk for bladder cancer.
Clinical application of NMP22 in the management of transitional cell carcinoma of the bladder.2000
Multicenter trial of the quantitative BTA TRAK assay in the detection of bladder cancer.1999
The role of fluorescence in situ hybridization assay for surveillance of non-muscle invasive bladder cancer.2010
A multigene urine test for the detection and stratification of bladder cancer in patients presenting with hematuria.2012
Clinical usefulness of fluorescence in situ hybridization for diagnosis and surveillance of bladder cancer.2010
Adjuvant therapy of T1 bladder carcinoma: preliminary results of an EORTC randomized study.1978
Single dose intravesical thiotepa as an adjuvant to cystodiathermy in the treatment of transitional cell bladder carcinoma.1976
The 4th study of prophylactic intravesical chemotherapy with adriamycin in the treatment of superficial bladder cancer: the experience of the Japanese Urological Cancer Research Group for Adriamycin.
A prospective randomized study of prophylaxis of tumor recurrence following transurethral resection of superficial bladder cancer--intravesical thio-TEPA versus oral UFT.
Intravesical instillations of 4-epi-doxorubicin (epirubicin) in the prophylactic treatment of superficial bladder cancer: results of a controlled prospective study.1992
Prophylactic instillation therapy of superficial bladder cancer. A randomized study comparing mitomycin C and adriamycin with special reference to DNA ploidy.1991
A low dose bacillus Calmette-Guerin regimen in superficial bladder cancer therapy: is it effective?1991
Intravesical Bacillus Calmette-Guérin prophylactic treatment for superficial bladder tumors: results of a controlled prospective study.1990
Intravesical mitomycin C instillation as a prophylactic treatment of superficial bladder tumor.1989
Prophylactic intravesical instillation therapy with adriamycin and mitomycin C in patients with superficial bladder cancer.
Comparative analysis of short-term and long-term prophylactic intravesical chemotherapy of superficial bladder cancer. Prospective, randomized, controlled studies of the Japanese Urological Cancer Research Group.
Bacillus Calmette-Guérin therapy alters the progression of superficial bladder cancer.1988
Adjuvant chemotherapy of superficial transitional cell bladder carcinoma: preliminary results of a European organization for research on treatment of cancer. Randomized trial comparing doxorubicin hydrochloride, ethoglucid and transurethral resection alone.1984
Randomized clinical trial on chemoprophylaxis of recurrence in cases of superficial bladder cancer.1983
The use of intravesical thio-tepa in the management of non-invasive carcinoma of the bladder.1981
A controlled trial of single dose intravesical adriamycin in superficial bladder tumours.1981
Prophylactic chemotherapy with intravesical instillation of adriamycin and oral administration of 5-fluorouracil after surgery for superficial bladder cancer. The Japanese Urological Cancer Research Group for Adriamycin.
The effect of intravesical thiotepa on tumour recurrence after endoscopic treatment of newly diagnosed superficial bladder cancer. A further report with long-term follow-up of a Medical Research Council randomized trial. Medical Research Council Working Party on Urological Cancer, Subgroup on Superficial Bladder Cancer.
Intravesical 4'-epi-doxorubicin (epirubicin) versus bacillus Calmette-Guérin. A controlled prospective study on the prophylaxis of superficial bladder cancer.1993
A prospective European Organization for Research and Treatment of Cancer Genitourinary Group randomized trial comparing transurethral resection followed by a single intravesical instillation of epirubicin or water in single stage Ta, T1 papillary carcinoma of the bladder.1993
The effect of intravesical mitomycin C on recurrence of newly diagnosed superficial bladder cancer: a further report with 7 years of follow up.1996
A randomized multicenter trial of adjuvant therapy in superficial bladder cancer: transurethral resection only versus transurethral resection plus mitomycin C versus transurethral resection plus bacillus Calmette-Guerin. Participating Clinics.1996
Intravesical instillation of epirubicin: effect on tumour recurrence in patients with dysplastic epithelium after transurethral resection of superficial bladder tumour.1996
Results at 43 months' follow-up of a double-blind, randomized, prospective clinical trial using intravesical interferon alpha-2b in the prophylaxis of stage pT1 transitional cell carcinoma of the bladder.1997
Single-dose versus multiple instillations of epirubicin as prophylaxis for recurrence after transurethral resection of pTa and pT1 transitional-cell bladder tumours: a prospective, randomized controlled study.1997
Intravesical epirubicin versus doxorubicin for superficial bladder tumors (stages pTa and pT1): a randomized prospective study.1997
Adjuvant chemotherapy for superficial transitional cell bladder carcinoma: long-term results of a European Organization for Research and Treatment of Cancer randomized trial comparing doxorubicin, ethoglucid and transurethral resection alone.1997
Efficacy of escalating doses of intravesical interferon alpha-2b in reducing recurrence rate and progression in superficial transitional cell carcinoma.1998
Effectiveness of a single immediate mitomycin C instillation in patients with low risk superficial bladder cancer: short and long-term followup.
Randomized study of single early instillation of (2"R)-4'-O-tetrahydropyranyl-doxorubicin for a single superficial bladder carcinoma.2002
Perioperative single dose instillation of epirubicin or interferon-alpha after transurethral resection for the prophylaxis of primary superficial bladder cancer recurrence: a prospective randomized multicenter study--FinnBladder III long-term results.2002
Intravesical instillations of interferon gamma in the prophylaxis of high risk superficial bladder cancer--results of a controlled prospective study.2002
The immunomodulating effect of interferon-gamma intravesical instillations in preventing bladder cancer recurrence.
17-year follow-up of a randomized prospective controlled trial of adjuvant intravesical doxorubicin in the treatment of superficial bladder cancer.-- Not Found --
A single instillation of epirubicin after transurethral resection of bladder tumors prevents only small recurrences.2008
Should all patients with non-muscle-invasive bladder cancer receive early intravesical chemotherapy after transurethral resection? The results of a prospective randomised multicentre study.2009
Single postoperative instillation of gemcitabine in patients with non-muscle-invasive transitional cell carcinoma of the bladder: a randomised, double-blind, placebo-controlled phase III multicentre study.
Two instillations of epirubicin as prophylaxis for recurrence after transurethral resection of Ta and T1 transitional cell bladder cancer: a prospective, randomized controlled study.2010
Long-term experience with early single mitomycin C instillations in patients with low-risk non-muscle-invasive bladder cancer: prospective, single-centre randomised trial.2011
Comparative analysis of short-term and long-term prophylactic intravesical chemotherapy of superficial bladder cancer. Prospective, randomized, controlled studies of the Japanese Urological Cancer Research Group.1987
A randomized trial of radical radiotherapy for the management of pT1G3 NXM0 transitional cell carcinoma of the bladder.2007
Prognosis and treatment of T1G3 bladder tumours. A prognostic factor analysis of 121 patients. Dutch South Eastern Bladder Cancer Study Group.1994
5-aminolaevulinic acid-induced fluorescence cystoscopy during transurethral resection reduces the risk of recurrence in stage Ta/T1 bladder cancer.2005
Photodynamic diagnosis of non-muscle invasive bladder cancer using hexaminolevulinic acid.2011
Clinically relevant improvement of recurrence-free survival with 5-aminolevulinic acid induced fluorescence diagnosis in patients with superficial bladder tumors.2002
HAL blue-light cystoscopy in high-risk nonmuscle-invasive bladder cancer--re-TURBT recurrence rates in a prospective, randomized study.2010
Treatment changes and long-term recurrence rates after hexaminolevulinate (HAL) fluorescence cystoscopy: does it really make a difference in patients with non-muscle-invasive bladder cancer (NMIBC)?2012
Fluorescence-guided transurethral resection of bladder tumours reduces bladder tumour recurrence due to less residual tumour tissue in Ta/T1 patients: a randomized two-centre study.2011
Hexaminolevulinate-induced fluorescence versus white light during transurethral resection of noninvasive bladder tumor: does it reduce recurrences?2012
Transurethral resection for bladder cancer using 5-aminolevulinic acid induced fluorescence endoscopy versus white light endoscopy.
A randomized prospective trial to assess the impact of transurethral resection in narrow band imaging modality on non-muscle-invasive bladder cancer recurrence.
Prospective randomized trial of hexylaminolevulinate photodynamic-assisted transurethral resection of bladder tumour (TURBT) plus single-shot intravesical mitomycin C vs conventional white-light TURBT plus mitomycin C in newly presenting non-muscle-invasive bladder cancer.2013
Fluorescence endoscopy with 5-aminolevulinic acid reduces early recurrence rate in superficial bladder cancer.2001
Transurethral resection of non-muscle-invasive bladder transitional cell cancers with or without 5-aminolevulinic Acid under visible and fluorescent light: results of a prospective, randomised, multicentre study.2010
Hexaminolevulinate guided fluorescence cystoscopy reduces recurrence in patients with nonmuscle invasive bladder cancer.
Detection and clinical outcome of urinary bladder cancer with 5-aminolevulinic acid-induced fluorescence cystoscopy : A multicenter randomized, double-blind, placebo-controlled trial.2011
Randomized phase III trial on gemcitabine versus mytomicin in recurrent superficial bladder cancer: evaluation of efficacy and tolerance.2010
Urinary dosage of nuclear matrix protein 22 (NMP22) like biologic marker of transitional cell carcinoma (TCC): a study on patients with hematuria.1999
Clinical experience with BCG alone versus BCG plus epirubicin.2000
Prophylaxis of superficial bladder cancer with mitomycin or interferon alfa-2b: results of a multicentric Italian study.1994
Experience with bacillus Calmette-Guerin in patients with superficial bladder carcinoma.1982
Can early single dose instillation of epirubicin improve bacillus Calmette-Guerin efficacy in patients with nonmuscle invasive high risk bladder cancer? Results from a prospective, randomized, double-blind controlled study.2008
Twelve-year follow up of a randomized prospective trial comparing bacillus Calmette-Guerin and epirubicin as adjuvant therapy in superficial bladder cancer.2005
The effects of intravesical chemoimmunotherapy with gemcitabine and Bacillus Calmette-Guérin in superficial bladder cancer: a preliminary study.
Bacillus Calmette-Guerin versus epirubicin for primary, secondary or concurrent carcinoma in situ of the bladder: results of a European Organization for the Research and Treatment of Cancer--Genito-Urinary Group Phase III Trial (30906).2005
BCG-RIVM versus BCG-Tice versus mitomycin-C in superficial bladder cancer. Rationale, design, and interim analysis of the trial of the South-East Cooperative Urological Group, The Netherlands.1992
Gemcitabine versus bacille Calmette-Guérin after initial bacille Calmette-Guérin failure in non-muscle-invasive bladder cancer: a multicenter prospective randomized trial.2010
Intravesical electromotive mitomycin C versus passive transport mitomycin C for high risk superficial bladder cancer: a prospective randomized study.2003
Bacillus Calmette-Guérin is superior to a combination of epirubicin and interferon-alpha2b in the intravesical treatment of patients with stage T1 urinary bladder cancer. A prospective, randomized, Nordic study.2010
Comparison of the prophylactic usefulness of epirubicin and doxorubicin in the treatment of superficial bladder cancer by intravesical instillation: a multicenter randomized trial. Kobe University Urological Oncology Group.
A trial of prophylactic thiotepa or mitomycin C intravesical therapy in patients with recurrent or multiple superficial bladder cancers.1986
Long-term intravesical adjuvant chemotherapy further reduces recurrence rate compared with short-term intravesical chemotherapy and short-term therapy with Bacillus Calmette-Guérin (BCG) in patients with non-muscle-invasive bladder carcinoma.2007
The immunomodulating effect of interferon-gamma intravesical instillations in preventing bladder cancer recurrence.2003
The impact of intravesical gemcitabine and 1/3 dose Bacillus Calmette-Guérin instillation therapy on the quality of life in patients with nonmuscle invasive bladder cancer: results of a prospective, randomized, phase II trial.2013
The value of perioperative mitomycin C instillation in improving subsequent bacillus calmette-guerin instillation efficacy in intermediate and high-risk patients with non-muscle invasive bladder cancer: a prospective randomized study.-- Not Found --
Maintenance therapy with bacillus Calmette-Guérin Connaught strain clearly prolongs recurrence-free survival following transurethral resection of bladder tumour for non-muscle-invasive bladder cancer.
Sustained prophylactic effect of intravesical bacille Calmette-Guérin for superficial bladder cancer: a smoothed hazard analysis in a randomized prospective study.2006
Comparison of different schedules of cytostatic intravesical instillations in patients with superficial bladder carcinoma: final evaluation of a prospective multicenter study with 419 patients.1990
Instillation of mitomycin C and doxorubicin in the prevention of recurrent superficial (Ta-T1) bladder cancer.1987
Intravesical immunoprophylaxis in recurrent superficial bladder cancer (Stage T1): multicenter trial comparing bacille Calmette-Guérin and interferon-alpha.1997
Weekly mitomycin C followed by monthly bacillus Calmette-Guerin or alternating monthly interferon-alpha2B and bacillus Calmette-Guerin for prophylaxis of recurrent papillary superficial bladder carcinoma.2000
Alternating mitomycin C and BCG instillations versus BCG alone in treatment of carcinoma in situ of the urinary bladder: a nordic study.2003
A randomized trial of intravesical doxorubicin and immunotherapy with bacille Calmette-Guérin for transitional-cell carcinoma of the bladder.1991
Randomized intergroup comparison of bacillus calmette-guerin immunotherapy and mitomycin C chemotherapy prophylaxis in superficial transitional cell carcinoma of the bladder a southwest oncology group study.-- Not Found --
Maintenance bacillus Calmette-Guerin immunotherapy for recurrent TA, T1 and carcinoma in situ transitional cell carcinoma of the bladder: a randomized Southwest Oncology Group Study.2000
Randomized study of single instillation of epirubicin for superficial bladder carcinoma: long-term clinical outcomes.2006
A randomized prospective study comparing long-term intravesical instillations of mitomycin C and bacillus Calmette-Guerin in patients with superficial bladder carcinoma.1996
A randomized prospective study of intravesical prophylaxis in non-musle invasive bladder cancer at intermediate risk of recurrence: mitomycin chemotherapy vs BCG immunotherapy.2008
Bacillus Calmette-Guerin versus doxorubicin versus thiotepa: a randomized prospective study in 202 patients with superficial bladder cancer.1990
BCG versus epirubicin in the prophylaxis of multiple superficial bladder tumours: results of a prospective randomized study using modified treatment schemes.1996
Sequential chemoimmunotherapy using mitomycin followed by bacillus Calmette-Guerin (MCC + BCG) versus single-agent immunotherapy (BCG) for recurrent superficial bladder tumors2010
Bacillus Calmette-Guérin with or without interferon α-2b and megadose versus recommended daily allowance vitamins during induction and maintenance intravesical treatment of nonmuscle invasive bladder cancer.2010
A multicentre, randomised prospective trial comparing three intravesical adjuvant therapies for intermediate-risk superficial bladder cancer: low-dose bacillus Calmette-Guerin (27 mg) versus very low-dose bacillus Calmette-Guerin (13.5 mg) versus mitomycin C.2007
Sequential intravesical chemoimmunotherapy with mitomycin C and bacillus Calmette-Guérin and with bacillus Calmette-Guérin alone in patients with carcinoma in situ of the urinary bladder: results of an EORTC genito-urinary group randomized phase 2 trial (30993).
Bacillus Calmette-Guérin versus gemcitabine for intravesical therapy in high-risk superficial bladder cancer: a randomised prospective study.2010
Transurethral resection with perioperative instilation on interferon-alpha or epirubicin for the prophylaxis of recurrent primary superficial bladder cancer: a prospective randomized multicenter study--Finnbladder III.1999
Intravesical chemotherapy (mitomycin C) versus immunotherapy (bacillus Calmette-Guérin) in superficial bladder cancer.1991
Alternating mitomycin C and bacillus Calmette-Guerin instillation therapy for carcinoma in situ of the bladder. The Finnbladder Group.1995
Alternating mitomycin C and bacillus Calmette-Guerin instillation prophylaxis for recurrent papillary (stages Ta to T1) superficial bladder cancer. Finnbladder Group.1996
A phase II study of prophylactic intravesical chemotherapy with 4'-epirubicin in recurrent superficial bladder cancer: comparison of 4'-epirubicin and adriamycin.1994
Intravesical instillation of epirubicin, bacillus Calmette-Guerin and bacillus Calmette-Guerin plus isoniazid for intermediate and high risk Ta, T1 papillary carcinoma of the bladder: a European Organization for Research and Treatment of Cancer genito-urinary group randomized phase III trial.2001
A randomised prospective study comparing intravesical instillations of mitomycin-C, BCG-Tice, and BCG-RIVM in pTa-pT1 tumours and primary carcinoma in situ of the urinary bladder. Dutch South-East Cooperative Urological Group.1993
Long-term follow-up of an EORTC randomized prospective trial comparing intravesical bacille Calmette-Guérin-RIVM and mitomycin C in superficial bladder cancer. EORTC GU Group and the Dutch South East Cooperative Urological Group. European Organisation for Research and Treatment of Cancer Genito-Urinary Tract Cancer Collaborative Group.1998
Intravesical thiotepa and mitomycin C treatment immediately after transurethral resection and later for superficial (stages Ta and Tis) bladder cancer: a prospective, randomized, stratified study with crossover design.1985
Methods to improve efficacy of intravesical mitomycin C: results of a randomized phase III trial.2001
A prospective randomized trial of maintenance versus nonmaintenance intravesical bacillus Calmette-Guérin therapy of superficial bladder cancer.1987
Intravesical adjuvant chemotherapy for superficial transitional cell bladder carcinoma: results of 2 European Organization for Research and Treatment of Cancer randomized trials with mitomycin C and doxorubicin comparing early versus delayed instillations and short-term versus long-term treatment. European Organization for Research and Treatment of Cancer Genitourinary Group.1995
Neoadjuvant short-term intensive intravesical mitomycin C regimen compared with weekly schedule for low-grade recurrent non-muscle-invasive bladder cancer: preliminary results of a randomised phase 2 study.2012
Single early instillation of mitomycin C and urinary alkalinization in low-risk non-muscle-invasive bladder cancer: a preliminary study.2013
Marker tumour response to Evans and Pasteur bacille Calmette-Guérin in multiple recurrent pTa/pT1 bladder tumours: report from the Medical Research Council Subgroup on Superficial Bladder Cancer (Urological Cancer Working Party).1994
Long-term versus short-term doxorubicin hydrochloride instillation after transurethral resection of superficial bladder cancer.1990
Clinical use of urinary markers for the detection and prognosis of bladder carcinoma: a comparison of immunocytology with monoclonal antibodies against Lewis X and 486p3/12 with the BTA STAT and NMP22 tests.2002
Intravesical combination chemotherapy with mitomycin C and doxorubicin for superficial bladder cancer: a randomized trial of maintenance versus no maintenance following a complete response.
Analysis of progression and survival after 10 years of a randomized prospective study comparing mitomycin-C and bacillus Calmette-Guérin in patients with high-risk bladder cancer.2007
A randomized controlled study of intravesical alpha-2b-interferon in carcinoma in situ of the bladder.1990
A 12 versus 6-week course of bacillus Calmette-Guerin prophylaxis for the treatment of high risk superficial bladder cancer.1997
Comparison of three schedules of intravesical epirubicin in patients with non-muscle-invasive bladder cancer.2008
Maintenance therapy with bacillus Calmette-Guérin Connaught strain clearly prolongs recurrence-free survival following transurethral resection of bladder tumour for non-muscle-invasive bladder cancer.2011
How effective is topical alpha-2b interferon in preventing recurrence of superficial bladder cancer?1991
Comparable effect with minimal morbidity of low-dose Tokyo 172 strain compared with regular dose Connaught strain as an intravesical bacillus Calmette-Guérin prophylaxis in nonmuscle invasive bladder cancer: Results of a randomized prospective comparison.2013
Sufficient prophylactic efficacy with minor adverse effects by intravesical instillation of low-dose bacillus Calmette-Guérin for superficial bladder cancer recurrence.2003
A randomized controlled trial of short-term versus long-term prophylactic intravesical instillation chemotherapy for recurrence after transurethral resection of Ta/T1 transitional cell carcinoma of the bladder.2004
Maintenance intravesical bacillus Calmette-Guérin instillation for Ta, T1 cancer and carcinoma in situ of the bladder: randomized controlled trial by the BCG Tokyo Strain Study Group.2010
Effect of prophylactic treatment with intravesical epirubicin on recurrence of superficial bladder cancer--The 6th Trial of the Japanese Urological Cancer Research Group (JUCRG): a randomized trial of intravesical epirubicin at dose of 20mg/40ml, 30mg/40ml, 40mg/40ml.2004
A randomized comparative dose-ranging study of interferon-alpha and mitomycin-C as an internal control in primary or recurrent superficial transitional cell carcinoma of the bladder.
Long-term follow-up of a randomized prospective trial comparing a standard 81 mg dose of intravesical bacille Calmette-Guérin with a reduced dose of 27 mg in superficial bladder cancer.2002
Has a 3-fold decreased dose of bacillus Calmette-Guerin the same efficacy against recurrences and progression of T1G3 and Tis bladder tumors than the standard dose? Results of a prospective randomized trial.2005
Intravesical chemotherapy with epirubicin: a dose response study.1999
Early and large-dose intravesical instillation of epirubicin to prevent superficial bladder carcinoma recurrence after transurethral resection.2004
Dose-response of bacillus Calmette-Guerin in the treatment of superficial bladder cancer.1992
Intravesical BCG treatment for superficial bladder cancer: long-term results using two different strains of BCG.1992
Intravesical adjuvant chemotherapy for superficial transitional cell bladder carcinoma: results of a randomized trial with epirubicin comparing short-term versus long-term maintenance treatment.2002
Final results of an EORTC-GU cancers group randomized study of maintenance bacillus Calmette-Guérin in intermediate- and high-risk Ta, T1 papillary carcinoma of the urinary bladder: one-third dose versus full dose and 1 year versus 3 years of maintenance.2013
A randomized study of short-versus long-term intravesical epirubicin instillation for superficial bladder cancer. Nagoya University Urological Oncology Group.1998
Improving the efficacy of BCG immunotherapy by dose reduction.1995
Control group and maintenance treatment with bacillus Calmette-Guerin for carcinoma in situ and/or high grade bladder tumors.2001
Bacillus Calmette-Guérin strain differences have an impact on clinical outcome in bladder cancer immunotherapy.2014
Natural history and treatment of low and high risk superficial bladder tumors.1988
Long-term follow-up of cytostatic intravesical instillation in patients with superficial bladder carcinoma. Is short-term, intensive instillation better than maintenance therapy?1997
A prospective comparative study of intravesical bacillus Calmette-Guérin therapy with the Tokyo or Connaught strain for nonmuscle invasive bladder cancer.2013
Comparison of the efficacy of single or double intravesical epirubicin instillation in the early postoperative period to prevent recurrences in non-muscle-invasive urothelial carcinoma of the bladder: prospective, randomized multicenter study.2010
Adjuvant chemotherapy with early intravesical instillation of adriamycin and long-term oral administration of 5-fluorouracil in superficial bladder cancer. The Kyushu University Urological Oncology Group.1992
A 1-year maintenance after early adjuvant intravesical chemotherapy has a limited efficacy in preventing recurrence of intermediate risk non-muscle-invasive bladder cancer.2010

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