Intravesical Therapy for the Treatment of Nonmuscle Invasive Bladder Cancer: A Systematic Review and Meta-Analysis

Roger Chou, Shelley Selph, David Buckley, Rongwei (Rochelle) Fu, Jessica C. Griffin, Sara Grusing, John L. Gore

Research output: Contribution to journalArticle

41 Citations (Scopus)

Abstract

Purpose: We systematically review the benefits and harms of intravesical therapies for nonmuscle invasive bladder cancer. Materials and Methods: Systematic literature searches were performed of Ovid MEDLINE (January 1990 through February 2016), the Cochrane databases and reference lists. Randomized and quasi-randomized trials of intravesical bacillus Calmette-Guérin, mitomycin C, gemcitabine, thiotepa, valrubicin, doxorubicin, epirubicin and interferon vs transurethral bladder tumor resection alone, and head-to-head trials of intravesical therapies were selected. Data were pooled using a random effects model. Results: Overall 39 trials evaluated adjuvant intravesical therapy vs transurethral bladder tumor resection alone. Bacillus Calmette-Guérin was associated with a decreased risk of bladder cancer recurrence (3 trials, RR 0.56, 95% CI 0.43-0.71) and progression (4 trials, RR 0.39, 95% CI 0.24-0.64) (strength of evidence low). Mitomycin C, doxorubicin, epirubicin and thiotepa were also associated with a decreased risk of recurrence, with no difference in risk of progression (strength of evidence low). There were 55 trials that compared one intravesical therapy agent against another. There were no differences between bacillus Calmette-Guérin vs mitomycin C in recurrence risk (RR 0.95, 95% CI 0.81-1.11), but bacillus Calmette-Guérin was associated with a decreased risk of recurrence in the subgroup of trials of maintenance regimens (RR 0.79, 95% CI 0.71-0.87, strength of evidence low). Bacillus Calmette-Guérin was associated with a lower recurrence risk vs doxorubicin, epirubicin, interferon alpha-2a, bacillus Calmette-Guérin plus interferon alpha-2b, and thiotepa (strength of evidence low to moderate). Bacillus Calmette-Guérin was associated with higher rates of local and systemic adverse events than other intravesical agents (strength of evidence low). Head-to-head trials showed no clear differences between standard and lower doses of bacillus Calmette-Guérin in recurrence, progression or mortality risk (strength of evidence low). Limited evidence suggested that bacillus Calmette-Guérin maintenance regimens are associated with reduced recurrence risk vs no further intravesical therapy in responders to induction therapy (strength of evidence low). Conclusions: For nonmuscle invasive bladder cancer several intravesical therapies are associated with a decreased risk of recurrence vs transurethral bladder tumor resection alone. Bacillus Calmette-Guérin is the only agent associated with a decreased progression risk vs transurethral bladder tumor resection alone, but may be associated with a higher risk of adverse events than other intravesical therapies, indicating trade-offs between potential benefits and harms.

Original languageEnglish (US)
JournalJournal of Urology
DOIs
StateAccepted/In press - 2017

Fingerprint

Urinary Bladder Neoplasms
Meta-Analysis
Bacillus
Recurrence
Thiotepa
Epirubicin
Mitomycin
Therapeutics
Doxorubicin
interferon alfa-2b
valrubicin
gemcitabine
Maintenance
MEDLINE
Interferons
Databases
Mortality

Keywords

  • Administration
  • BCG vaccine
  • Interferons
  • Intravesical
  • Mitomycin
  • Urinary bladder neoplasms

ASJC Scopus subject areas

  • Urology

Cite this

@article{7ddce71ba624487d95d9347705fd4753,
title = "Intravesical Therapy for the Treatment of Nonmuscle Invasive Bladder Cancer: A Systematic Review and Meta-Analysis",
abstract = "Purpose: We systematically review the benefits and harms of intravesical therapies for nonmuscle invasive bladder cancer. Materials and Methods: Systematic literature searches were performed of Ovid MEDLINE (January 1990 through February 2016), the Cochrane databases and reference lists. Randomized and quasi-randomized trials of intravesical bacillus Calmette-Gu{\'e}rin, mitomycin C, gemcitabine, thiotepa, valrubicin, doxorubicin, epirubicin and interferon vs transurethral bladder tumor resection alone, and head-to-head trials of intravesical therapies were selected. Data were pooled using a random effects model. Results: Overall 39 trials evaluated adjuvant intravesical therapy vs transurethral bladder tumor resection alone. Bacillus Calmette-Gu{\'e}rin was associated with a decreased risk of bladder cancer recurrence (3 trials, RR 0.56, 95{\%} CI 0.43-0.71) and progression (4 trials, RR 0.39, 95{\%} CI 0.24-0.64) (strength of evidence low). Mitomycin C, doxorubicin, epirubicin and thiotepa were also associated with a decreased risk of recurrence, with no difference in risk of progression (strength of evidence low). There were 55 trials that compared one intravesical therapy agent against another. There were no differences between bacillus Calmette-Gu{\'e}rin vs mitomycin C in recurrence risk (RR 0.95, 95{\%} CI 0.81-1.11), but bacillus Calmette-Gu{\'e}rin was associated with a decreased risk of recurrence in the subgroup of trials of maintenance regimens (RR 0.79, 95{\%} CI 0.71-0.87, strength of evidence low). Bacillus Calmette-Gu{\'e}rin was associated with a lower recurrence risk vs doxorubicin, epirubicin, interferon alpha-2a, bacillus Calmette-Gu{\'e}rin plus interferon alpha-2b, and thiotepa (strength of evidence low to moderate). Bacillus Calmette-Gu{\'e}rin was associated with higher rates of local and systemic adverse events than other intravesical agents (strength of evidence low). Head-to-head trials showed no clear differences between standard and lower doses of bacillus Calmette-Gu{\'e}rin in recurrence, progression or mortality risk (strength of evidence low). Limited evidence suggested that bacillus Calmette-Gu{\'e}rin maintenance regimens are associated with reduced recurrence risk vs no further intravesical therapy in responders to induction therapy (strength of evidence low). Conclusions: For nonmuscle invasive bladder cancer several intravesical therapies are associated with a decreased risk of recurrence vs transurethral bladder tumor resection alone. Bacillus Calmette-Gu{\'e}rin is the only agent associated with a decreased progression risk vs transurethral bladder tumor resection alone, but may be associated with a higher risk of adverse events than other intravesical therapies, indicating trade-offs between potential benefits and harms.",
keywords = "Administration, BCG vaccine, Interferons, Intravesical, Mitomycin, Urinary bladder neoplasms",
author = "Roger Chou and Shelley Selph and David Buckley and Fu, {Rongwei (Rochelle)} and Griffin, {Jessica C.} and Sara Grusing and Gore, {John L.}",
year = "2017",
doi = "10.1016/j.juro.2016.12.090",
language = "English (US)",
journal = "Journal of Urology",
issn = "0022-5347",
publisher = "Elsevier Inc.",

}

TY - JOUR

T1 - Intravesical Therapy for the Treatment of Nonmuscle Invasive Bladder Cancer

T2 - A Systematic Review and Meta-Analysis

AU - Chou, Roger

AU - Selph, Shelley

AU - Buckley, David

AU - Fu, Rongwei (Rochelle)

AU - Griffin, Jessica C.

AU - Grusing, Sara

AU - Gore, John L.

PY - 2017

Y1 - 2017

N2 - Purpose: We systematically review the benefits and harms of intravesical therapies for nonmuscle invasive bladder cancer. Materials and Methods: Systematic literature searches were performed of Ovid MEDLINE (January 1990 through February 2016), the Cochrane databases and reference lists. Randomized and quasi-randomized trials of intravesical bacillus Calmette-Guérin, mitomycin C, gemcitabine, thiotepa, valrubicin, doxorubicin, epirubicin and interferon vs transurethral bladder tumor resection alone, and head-to-head trials of intravesical therapies were selected. Data were pooled using a random effects model. Results: Overall 39 trials evaluated adjuvant intravesical therapy vs transurethral bladder tumor resection alone. Bacillus Calmette-Guérin was associated with a decreased risk of bladder cancer recurrence (3 trials, RR 0.56, 95% CI 0.43-0.71) and progression (4 trials, RR 0.39, 95% CI 0.24-0.64) (strength of evidence low). Mitomycin C, doxorubicin, epirubicin and thiotepa were also associated with a decreased risk of recurrence, with no difference in risk of progression (strength of evidence low). There were 55 trials that compared one intravesical therapy agent against another. There were no differences between bacillus Calmette-Guérin vs mitomycin C in recurrence risk (RR 0.95, 95% CI 0.81-1.11), but bacillus Calmette-Guérin was associated with a decreased risk of recurrence in the subgroup of trials of maintenance regimens (RR 0.79, 95% CI 0.71-0.87, strength of evidence low). Bacillus Calmette-Guérin was associated with a lower recurrence risk vs doxorubicin, epirubicin, interferon alpha-2a, bacillus Calmette-Guérin plus interferon alpha-2b, and thiotepa (strength of evidence low to moderate). Bacillus Calmette-Guérin was associated with higher rates of local and systemic adverse events than other intravesical agents (strength of evidence low). Head-to-head trials showed no clear differences between standard and lower doses of bacillus Calmette-Guérin in recurrence, progression or mortality risk (strength of evidence low). Limited evidence suggested that bacillus Calmette-Guérin maintenance regimens are associated with reduced recurrence risk vs no further intravesical therapy in responders to induction therapy (strength of evidence low). Conclusions: For nonmuscle invasive bladder cancer several intravesical therapies are associated with a decreased risk of recurrence vs transurethral bladder tumor resection alone. Bacillus Calmette-Guérin is the only agent associated with a decreased progression risk vs transurethral bladder tumor resection alone, but may be associated with a higher risk of adverse events than other intravesical therapies, indicating trade-offs between potential benefits and harms.

AB - Purpose: We systematically review the benefits and harms of intravesical therapies for nonmuscle invasive bladder cancer. Materials and Methods: Systematic literature searches were performed of Ovid MEDLINE (January 1990 through February 2016), the Cochrane databases and reference lists. Randomized and quasi-randomized trials of intravesical bacillus Calmette-Guérin, mitomycin C, gemcitabine, thiotepa, valrubicin, doxorubicin, epirubicin and interferon vs transurethral bladder tumor resection alone, and head-to-head trials of intravesical therapies were selected. Data were pooled using a random effects model. Results: Overall 39 trials evaluated adjuvant intravesical therapy vs transurethral bladder tumor resection alone. Bacillus Calmette-Guérin was associated with a decreased risk of bladder cancer recurrence (3 trials, RR 0.56, 95% CI 0.43-0.71) and progression (4 trials, RR 0.39, 95% CI 0.24-0.64) (strength of evidence low). Mitomycin C, doxorubicin, epirubicin and thiotepa were also associated with a decreased risk of recurrence, with no difference in risk of progression (strength of evidence low). There were 55 trials that compared one intravesical therapy agent against another. There were no differences between bacillus Calmette-Guérin vs mitomycin C in recurrence risk (RR 0.95, 95% CI 0.81-1.11), but bacillus Calmette-Guérin was associated with a decreased risk of recurrence in the subgroup of trials of maintenance regimens (RR 0.79, 95% CI 0.71-0.87, strength of evidence low). Bacillus Calmette-Guérin was associated with a lower recurrence risk vs doxorubicin, epirubicin, interferon alpha-2a, bacillus Calmette-Guérin plus interferon alpha-2b, and thiotepa (strength of evidence low to moderate). Bacillus Calmette-Guérin was associated with higher rates of local and systemic adverse events than other intravesical agents (strength of evidence low). Head-to-head trials showed no clear differences between standard and lower doses of bacillus Calmette-Guérin in recurrence, progression or mortality risk (strength of evidence low). Limited evidence suggested that bacillus Calmette-Guérin maintenance regimens are associated with reduced recurrence risk vs no further intravesical therapy in responders to induction therapy (strength of evidence low). Conclusions: For nonmuscle invasive bladder cancer several intravesical therapies are associated with a decreased risk of recurrence vs transurethral bladder tumor resection alone. Bacillus Calmette-Guérin is the only agent associated with a decreased progression risk vs transurethral bladder tumor resection alone, but may be associated with a higher risk of adverse events than other intravesical therapies, indicating trade-offs between potential benefits and harms.

KW - Administration

KW - BCG vaccine

KW - Interferons

KW - Intravesical

KW - Mitomycin

KW - Urinary bladder neoplasms

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