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Optimizing intravesical mitomycin C therapy in non-muscle-invasive bladder cancer

Nature Reviews Urology volume 11, pages 220–230 (2014)Cite this article

Subjects

Key Points

  • Mitomycin C (MMC) is a chemotherapeutic agent commonly used for intravesical treatment of non-muscle-invasive bladder cancer (NMIBC)

  • Physiological and pharmacological approaches, such as emptying of the bladder and urine alkalization, can be taken to optimize the pharmacokinetics and, therefore, increase the efficacy of MMC therapy

  • Newer approaches such as electromotive drug administration, chemohyperthermia, maintenance MMC-based regimens and combination of MMC with other intravesical agents have been shown to increase efficacy of therapy using this agent

  • Combining MMC with novel agents targeting treatment resistance mechanisms, such as fibroblast growth factor signalling, histone deacetylases and heat shock proteins, might improve outcomes in patients with NMIBC

  • Further study of mechanisms of resistance to MMC is a promising avenue of investigation that might lead to major advances in intravesical therapy

  • As we move towards precision medicine, the goal should be to pre-select patients who will benefit from MMC therapy and avoid or alter the treatment of predicted nonresponders

Abstract

Nearly three-quarters of all newly diagnosed urothelial cancers are non-muscle-invasive bladder cancers (NMIBCs). Although bladder-preserving surgery can be used to treat NMIBC, the rate of recurrence remains high. Intravesical chemotherapy has been shown to reduce the rate of NMIBC recurrence, and mitomycin C (MMC) has become the most commonly used intravesical cytotoxic agent. Despite the popularity of this agent in the treatment of NMIBCs, many questions regarding the optimal approach to MMC therapy remain unanswered. Strategies to enhance delivery of MMC have been well studied and multiple measures are recommended for implementation in routine clinical practice. In addition, less widely investigated techniques, such as hyperthermia and electromotive drug administration, have been shown to increase the efficacy of MMC therapy. Nevertheless, even when the current 'optimal' approaches to MMC administration are used, a large proportion of NMIBCs recur. This apparent treatment resistance might be overcome by combination of MMC with other agents that have different mechanisms of action and are unlikely to have cross-resistance. Study of the mechanisms of resistance is, therefore, important to identify key pathways underlying this phenomenon, which could be rationally targeted using specific combinations of drugs. Knowledge of these mechanisms might also reveal markers of responsiveness to therapy that could be used for patient selection.

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Authors and Affiliations

  1. Department of Urology, Center for Robotic and Laparoscopic Surgery, Glickman Urological and Kidney Institute, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, 44195, OH, USA

    Homayoun Zargar

  2. Department of Urology, Bristol Urological Institute, Southmead Hospital, Bristol, BS10 5NB, UK

    Jonathan Aning

  3. Departments of Surgery and Urology, Austin Health, 145 Studley Road, Heidelberg, Melbourne, 3084, VIC, Australia

    Joseph Ischia

  4. Department of Urological Sciences, Vancouver Prostate Centre, University of British Columbia, 2660 Oak Street, Vancouver, V6H 3Z6, BC, Canada

    Alan So & Peter Black

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H.Z., J.A. and J.I. researched the data for the article, H.Z., A.S. and P.B. made substantial contributions to discussion of content, and all authors contributed substantially to writing and review/editing of the manuscript before publication.

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Zargar, H., Aning, J., Ischia, J. et al. Optimizing intravesical mitomycin C therapy in non-muscle-invasive bladder cancer. Nat Rev Urol 11, 220–230 (2014). https://doi.org/10.1038/nrurol.2014.52

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