Treatment of Non-Metastatic Muscle-Invasive Bladder Cancer [Entered Retrospectively]

Project Summary Title and Description

Title
Treatment of Non-Metastatic Muscle-Invasive Bladder Cancer [Entered Retrospectively]
Description
Structured Abstract Objectives. Although the standard treatment for non-metastatic muscle-invasive bladder cancer is cystectomy and neoadjuvant chemotherapy, there is interest in bladder-preserving therapy as an alternative, and uncertainty about the need for and optimal extent of lymph node dissection and optimal chemotherapy regimens and timing of administration. Data Sources. Electronic databases (Ovid MEDLINE, January 1990 to 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. We selected randomized controlled trials, nonrandomized controlled clinical trials and nonrandomized cohort studies with concurrent comparators that evaluated bladder-preserving therapies against one another or versus radical cystectomy, that evaluated the effectiveness of lymph node dissection or effects of extent of dissection, and that compared neoadjuvant or adjuvant chemotherapy versus another chemotherapy regimen or versus no chemotherapy. The quality of included studies was assessed, data were extracted, and results were summarized qualitatively and using meta-analysis. Results. One randomized controlled trial with methodological limitations found no difference between bladder preserving external beam radiation therapy (60 Gray) versus radical cystectomy plus radiation therapy (40 Gray) in median survival duration, though bladder-preserving treatment was associated with increased risk of local or regional recurrence (35.8% vs. 6.8%) (strength of evidence: insufficient). Cohort studies of bladder-preserving treatments versus radical cystectomy had methodological shortcomings and reported inconsistent results, precluding reliable conclusions (strength of evidence: insufficient). Cohort studies suggested that lymph node dissection was associated with lower risk of mortality than no lymph node dissection and that more extensive lymph node dissection with cystectomy might be more effective than less extensive lymph node dissection at improving survival, but studies had methodological limitations, there was some inconsistency in results, and there was variability in the lymph node dissection techniques evaluated (strength of evidence: low). Six randomized controlled trials consistently found neoadjuvant chemotherapy with cisplatin-based combination regimens associated with decreased risk, or a trend towards decreased risk, of mortality versus no neoadjuvant chemotherapy, including three trials that evaluated current regimens (cisplatin, methotrexate, and vinblastine and methotrexate, vinblastine, doxorubicin, and cisplatin (strength of evidence: moderate). Four trials found adjuvant chemotherapy associated with decreased risk of mortality versus no adjuvant chemotherapy, but no trial reported a statistically significant effect and there was some inconsistency in findings (strength of evidence: low). One trial and two cohort studies found no clear differences between neoadjuvant and adjuvant methotrexate, vinblastine, doxorubicin, and cisplatin in survival (strength of evidence: low). Evidence on harms, effectiveness of treatments for muscle-invasive bladder cancer in patient subgroups (including older patients, patients with comorbidities, and patients with renal dysfunction), and comparative effectiveness of different chemotherapy regimens was too limited to reach reliable conclusions. Conclusions. Neoadjuvant chemotherapy with cisplatinum-based regimens improved survival in patients with muscle-invasive bladder cancer, and extended lymph node dissection during cystectomy might be more effective than standard lymph node dissection for improving survival. More research is needed to clarify the effectiveness of bladder-preserving therapies versus radical cystectomy and define patient subgroups in which such therapies may be a potential option.
Attribution
N/A
Authors of Report
N/A
Methodology description
Review Methods. We selected randomized controlled trials, nonrandomized controlled clinical trials and nonrandomized cohort studies with concurrent comparators that evaluated bladder-preserving therapies against one another or versus radical cystectomy, that evaluated the effectiveness of lymph node dissection or effects of extent of dissection, and that compared neoadjuvant or adjuvant chemotherapy versus another chemotherapy regimen or versus no chemotherapy. The quality of included studies was assessed, data were extracted, and results were summarized qualitatively and using meta-analysis.
PROSPERO
CRD42014013282
DOI
10.7301/Z0MG7MDZ
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; Month YEAR. www.effectivehealthcare.ahrq.gov/reports/final.cfm

Key Questions

1. Key Question 1. For patients with non-metastatic muscle-invasive bladder cancer, what is the effectiveness of bladder-preserving treatments (chemotherapy, external beam or interstitial radiation therapy, partial cystectomy, and/or maximal transurethral resection of bladder tumor) for decreasing mortality or improving other outcomes (e.g., recurrence, metastasis, quality of life, functional status) compared with cystectomy alone or cystectomy in combination with chemotherapy? a) Does the comparative effectiveness differ according to tumor characteristics, such as histology, stage, grade, size, or molecular/genetic markers? b) Does the comparative effectiveness differ according to patient characteristics, such as age, sex, ethnicity, performance status, or medical comorbidities such as chronic kidney disease? c) What is the comparative effectiveness of various combinations of agents and/or radiation therapy used for bladder-preserving chemotherapy? d) What is the effectiveness of different bladder-preserving treatments (chemotherapy, external beam or interstitial radiation therapy, partial cystectomy and/or maximal transurethral resection of bladder tumor) compared with one another?
2. Key Question 2. For patients with clinically non-metastatic muscle-invasive bladder cancer that is treated with cystectomy, does regional lymph node dissection improve outcomes compared with cystectomy alone? a) Does the comparative effectiveness differ according to tumor characteristics, such as histology, stage, grade, size, or molecular/genetic markers? b) Does the comparative effectiveness differ according to the extent of the regional lymph node dissection (e.g., as measured by the number of lymph nodes removed or the anatomic extent of dissection)?
3. Key Question 3. For patients with non-metastatic muscle-invasive bladder cancer that is treated with cystectomy, does neoadjuvant or adjuvant chemotherapy improve outcomes compared with cystectomy alone? a) What is the comparative effectiveness of various combinations of agents used for neoadjuvant or adjuvant chemotherapy? b) Does the comparative effectiveness of various combinations of agents used for neoadjuvant or adjuvant chemotherapy differ according to tumor characteristics, such as histology, stage, grade, size, or molecular/genetic markers? c) Does the comparative effectiveness differ according to patient characteristics, such as age, sex, ethnicity, performance status, or medical comorbidities such as chronic kidney disease? d) Does the comparative effectiveness of neoadjuvant or adjuvant chemotherapy differ according to dosing frequency and/or the timing of its administration relative to cystectomy?
4. Key Question 4. What are the comparative adverse effects of treatments for nonmetastatic muscle-invasive bladder cancer? a) 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
Radical cystectomy versus bladder-preserving therapy for muscle-invasive urothelial carcinoma: examining confounding and misclassification biasin cancer observational comparative effectiveness research.2013
Effects of age and comorbidity on treatment and survival of patients with muscle-invasive bladder cancer.2014
Long-term followup of all patients with muscle invasive (stages T2, T3 and T4) bladder carcinoma in a geographical region.
Radiotherapy with or without chemotherapy in muscle-invasive bladder cancer.2012
Radical therapy for muscle-infiltrating bladder cancer (cystectomy or radiotherapy): does age affect the final therapeutic benefit for the patient?2008
Similar treatment outcomes for radical cystectomy and radical radiotherapy in invasive bladder cancer treated at a United Kingdom specialist treatment center.2008
Survival after bladder-preservation with brachytherapy versus radical cystectomy; a single institution experience.2005
Response and progression-free survival in T2 to T4 bladder tumors treated with trimodality therapy with bladder preservation.2010
Treatment of advanced bladder cancer category T2 T3 and T4a. A randomized multicenter study of preoperative irradiation and cystectomy versus radical irradiation and early salvage cystectomy for residual tumor. DAVECA protocol 8201. Danish Vesical Cancer Group.
Bladder preservation in selected patients with muscle-invasive bladder cancer by complete transurethral resection of the bladder plus systemic chemotherapy: long-term follow-up of a phase 2 nonrandomized comparative trial with radical cystectomy.
Stage-specific impact of pelvic lymph node dissection on survival in patients with non-metastatic bladder cancer treated with radical cystectomy.2012
Does extended lymphadenectomy increase the morbidity of radical cystectomy?2004
The number of nodes removed as well as the template of the dissection is independently correlated to cancer-specific survival after radical cystectomy for muscle-invasive bladder cancer.2013
Outcome after radical cystectomy with limited or extended pelvic lymph node dissection.2008
Impact of the number of lymph nodes retrieved on outcome in patients with muscle invasive bladder cancer.2002
Surgical factors influence bladder cancer outcomes: a cooperative group report.2004
Extent of pelvic lymphadenectomy and its impact on outcome in patients diagnosed with bladder cancer: analysis of data from the Surveillance, Epidemiology and End Results Program data base.2003
Lymphadenectomy in patients with transitional cell carcinoma of the urinary bladder; significance for staging and prognosis.2000
Radical cystectomy: extending the limits of pelvic lymph node dissection improves survival for patients with bladder cancer confined to the bladder wall.1998
Role of pelvic lymph node dissection in lymph node-negative patients with invasive bladder cancer.2010
Stage-specific impact of extended versus standard pelvic lymph node dissection in radical cystectomy.2013
Super extended versus extended pelvic lymph node dissection in patients undergoing radical cystectomy for bladder cancer: a comparative study.2011
Adjuvant chemotherapy with cisplatin and gemcitabine versus chemotherapy at relapse in patients with muscle-invasive bladder cancer submitted to radical cystectomy: an Italian, multicenter, randomized phase III trial.2012
A role for neoadjuvant gemcitabine plus cisplatin in muscle-invasive urothelial carcinoma of the bladder: a retrospective experience.2008
Neoadjuvant chemotherapy with gemcitabine/cisplatin vs. methotrexate/vinblastine/doxorubicin/cisplatin for muscle-invasive urothelial carcinoma of the bladder: a retrospective analysis from the University of Southern California.2013
A randomized trial of radical cystectomy versus radical cystectomy plus cisplatin, vinblastine and methotrexate chemotherapy for muscle invasive bladder cancer.1996
Neoadjuvant chemotherapy plus cystectomy compared with cystectomy alone for locally advanced bladder cancer.2003
Neoadjuvant cisplatin, methotrexate, and vinblastine chemotherapy for muscle-invasive bladder cancer: a randomised controlled trial.1999
International phase III trial assessing neoadjuvant cisplatin, methotrexate, and vinblastine chemotherapy for muscle-invasive bladder cancer: long-term results of the BA06 30894 trial.2011
Randomised phase III study of neoadjuvant chemotherapy with methotrexate, doxorubicin, vinblastine and cisplatin followed by radical cystectomy compared with radical cystectomy alone for muscle-invasive bladder cancer: Japan Clinical Oncology Group Study JCOG0209.2014
Five-year followup of a prospective trial of radical cystectomy and neoadjuvant chemotherapy: Nordic Cystectomy Trial I. The Nordic Cooperative Bladder Cancer Study Group.1996
Comparison between neoadjuvant and adjuvant gemcitabine plus cisplatin chemotherapy for muscle-invasive bladder cancer.2013
Integrated therapy for locally advanced bladder cancer: final report of a randomized trial of cystectomy plus adjuvant M-VAC versus cystectomy with both preoperative and postoperative M-VAC.2001
Retrospective analysis of clinical outcomes with neoadjuvant cisplatin-based regimens for muscle-invasive bladder cancer.2012
Neoadjuvant chemotherapy with cisplatin and methotrexate in patients with muscle-invasive bladder tumours.2002
Neoadjuvant cisplatin-methotrexate chemotherapy for invasive bladder cancer -- Nordic cystectomy trial 2.2002
The role of adjuvant chemotherapy following cystectomy for invasive bladder cancer: a prospective comparative trial.1991
A comparison of the outcomes of neoadjuvant and adjuvant chemotherapy for clinical T2-T4aN0-N2M0 bladder cancer.2012
Relative efficacy of perioperative gemcitabine and cisplatin versus methotrexate, vinblastine, adriamycin, and cisplatin in the management of locally advanced urothelial carcinoma of the bladder.2012
Adjuvant chemotherapy in locally advanced bladder cancer. Final analysis of a controlled multicentre study1997

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