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    Adjuvant chemotherapy for muscle-invasive bladder cancer: a systematic review and meta-analysis of individual participant data from randomised controlled trials

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    Authors
    Burdett, S.
    Fisher, D. J.
    Vale, C. L.
    Bono, A. V.
    Clarke, Noel W
    Cognetti, F.
    Collette, L.
    Cote, R. J.
    Goebell, P. J.
    Groshen, S.
    Lehmann, J.
    Parmar, M. K. B.
    Rolevich, A. I.
    Sonntag, R. W.
    Sternberg, C. N.
    Stockle, M.
    Studer, U. E.
    Torti, F. M.
    Zhegalik, A. G.
    Tierney, J. F.
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    Affiliation
    MRC Clinical Trials Unit at UCL, London, UK.
    Issue Date
    2021
    
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    Abstract
    Context: Our prior systematic review and meta-analysis of individual participant data (IPD) suggesting a benefit of adjuvant chemotherapy for muscle-invasive bladder cancer was limited by the number and size of included randomised trials. We have updated results to include additional trials, providing the most up-to-date and reliable evidence of the effects of this treatment. Objective: To investigate the role of adjuvant cisplatin-based chemotherapy in the treatment of muscle-invasive bladder cancer. Evidence acquisition: Published and unpublished trials were sought via searches of bibliographic databases, trials registers, conference proceedings, and hand searching. Updated IPD were centrally collected, checked, and analysed. Results from individual randomised controlled trials (RCTs) were combined using a two-stage fixed-effect model. Prespecified analyses explored any variation in effect by trial and participant characteristics. Evidence synthesis: Analyses of ten RCTs (1183 participants) demonstrated a benefit of cisplatin-based adjuvant chemotherapy on overall survival (hazard ratio [HR] = 0.82, 95% confidence interval [CI] = 0.70-0.96, p = 0.02). This represents an absolute improvement in survival of 6% at 5 yr, from 50% to 56%, and a 9% absolute benefit when adjusted for age, sex, pT stage, and pN category (HR = 0.77, 95% CI = 0.65-0.92, p = 0.004). There was no clear evidence that the effect varied by trial or participant characteristics. Adjuvant chemotherapy was also shown to improve recurrence-free survival (HR = 0.71, 95% CI = 0.60-0.83, p < 0.001), locoregional recurrence-free survival (HR = 0.68, 95% CI = 0.55-0.85, p < 0.001), and metastasis-free survival (HR = 0.79, 95% CI = 0.65-0.95, p = 0.01), with absolute benefits of 11%, 11%, and 8%, respectively. Conclusions: This systematic review and meta-analysis demonstrates that cisplatin-based adjuvant chemotherapy is a valid option for improving outcomes for muscle-invasive bladder cancer.
    Citation
    Burdett S, Fisher DJ, Vale CL, Sternberg CN, Clarke NW, Parmar MKB, et al. Adjuvant Chemotherapy for Muscle-invasive Bladder Cancer: A Systematic Review and Meta-analysis of Individual Participant Data from Randomised Controlled Trials Vol. 81, European Urology. Elsevier BV; 2022. p. 50–61.
    Journal
    European Urology
    URI
    http://hdl.handle.net/10541/624944
    DOI
    10.1016/j.eururo.2021.09.028
    PubMed ID
    34802798
    Type
    Article
    ae974a485f413a2113503eed53cd6c53
    10.1016/j.eururo.2021.09.028
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