Intravesical chemotherapy plus bacille Calmette-Guérin in non-muscle invasive bladder cancer: a systematic review with meta-analysis

Authors

  • Baerin B. Houghton,

    1. National Health and Medical Research Council Clinical Trials Centre, University of Sydney, Sydney, NSW, Australia
    2. Australian and New Zealand Urogenital and Prostate (ANZUP) Cancer Trials Group Ltd, Sydney, NSW, Australia
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  • Venu Chalasani,

    1. National Health and Medical Research Council Clinical Trials Centre, University of Sydney, Sydney, NSW, Australia
    2. Australian and New Zealand Urogenital and Prostate (ANZUP) Cancer Trials Group Ltd, Sydney, NSW, Australia
    3. Northern Sydney Local Health District, Sydney, NSW, Australia
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  • Dickon Hayne,

    1. School of Surgery, University of Western Australia, Perth, WA, Australia
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  • Peter Grimison,

    1. Sydney Cancer Centre, Sydney, NSW, Australia
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  • Christopher S. B. Brown,

    1. National Health and Medical Research Council Clinical Trials Centre, University of Sydney, Sydney, NSW, Australia
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  • Manish I. Patel,

    1. Urological Cancers Outcomes Centre, University of Sydney, Sydney, NSW, Australia
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  • Ian D. Davis,

    1. Australian and New Zealand Urogenital and Prostate (ANZUP) Cancer Trials Group Ltd, Sydney, NSW, Australia
    2. Monash University, Melbourne, Vic., Australia
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  • Martin R. Stockler

    Corresponding author
    1. National Health and Medical Research Council Clinical Trials Centre, University of Sydney, Sydney, NSW, Australia
    2. Sydney Cancer Centre, Sydney, NSW, Australia
    • Correspondence: Martin Stockler; NHMRC Clinical Trials Centre, Medical Foundation Building, L5, University of Sydney, Sydney, NSW 2006, Australia.

      e-mail: martin.stockler@sydney.edu.au

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Abstract

What's known on the subject? and What does the study add?

  • Non-muscle-invasive bladder cancer has a significant recurrence and progression rate despite transurethral resection. The current standard of care to lower the risk of recurrence and progression is adjuvant BCG followed by maintenance BCG. Despite this, a significant number of patients experience recurrence and progress to invasive cancer. Several randomized trials have studied combination therapy (BCG with chemotherapy) to try to reduce the recurrence and progression rate.
  • We performed a systematic review with meta-analysis and found that adjuvant BCG followed by maintenance therapy is the appropriate standard of care when compared with combination therapy. We conclude that further trials are warranted to test the effects of adding chemotherapy to BCG in patients with Ta or T1 disease, but not in those with Tis alone.

Objective

  • To determine if the combination of intravesical chemotherapy and maintenance bacille Calmette-Guérin (BCG), used in sequence, is superior to maintenance BCG alone in the treatment of non-muscle-invasive bladder cancer (NMIBC).

Methods

  • We searched biomedical literature databases for randomized controlled trials that compared sequential, intravesical chemotherapy added to maintenance BCG with maintenance BCG alone.
  • Studies that did not use maintenance BCG were excluded.
  • The meta-analysis was performed using the fixed effects model.

Results

  • Four trials were identified, including 801 patients.
  • Adding chemotherapy to maintenance BCG did not result in a significant reduction in recurrence (relative risk [RR] 0.92; 95% confidence interval [CI] 0.79–1.09; P = 0.32) or progression (RR 0.88; 95% CI 0.61–1.27; P = 0.5).
  • The risk of recurrence (RR 0.75; 95% CI 0.61–0.92; P = 0.006) and progression (RR 0.45; 95% CI 0.25–0.81; P = 0.007) were reduced when the single trial that included isolated Tis was excluded.
  • Toxicity was similar for both groups.

Conclusions

  • Adjuvant therapy with induction BCG followed by maintenance BCG is the appropriate standard of care for patients with resected NMIBC at high risk of recurrence.
  • Further trials are warranted to test the effects of adding chemotherapy to BCG in patients with Ta or T1 disease, but not in those with Tis alone.

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