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  • Review Article
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Systemic, perioperative management of muscle-invasive bladder cancer and future horizons

Nature Reviews Clinical Oncology volume 14, pages 221–234 (2017)Cite this article

Subjects

Key Points

  • High metastatic relapse rates after radical cystectomy indicate muscle-invasive bladder cancer (MIBC) is a systemic disease at diagnosis in many patients

  • The use of adjuvant chemotherapy to decrease relapse rates after radical cystectomy is not supported by level 1 evidence, and the postoperative morbidity of patients often precludes such systemic treatment

  • For eligible patients, the standard-of-care treatment approach for MIBC comprises cisplatin-based neoadjuvant chemotherapy followed by radical cystectomy and bilateral pelvic lymph-node dissection

  • Barriers to improved patient outcomes include inaccurate clinical staging before selecting curative treatment, slow uptake of neoadjuvant chemotherapy, and the lack of an effective non-cisplatin-based neoadjuvant treatment regimen

  • Identification of genomic predictors of a response to chemotherapy might lead to a more-personalized approach to the treatment of patients with MIBC

  • Immunotherapy will probably reshape the MIBC treatment landscape

Abstract

Many patients diagnosed with muscle-invasive bladder cancer (MIBC) will develop distant metastatic disease. Over the past three decades, perioperative cisplatin-based chemotherapy has been investigated for its ability to reduce the number of deaths from bladder cancer. Insufficient evidence is available to fully support the use of such chemotherapy in the adjuvant setting; however, neoadjuvant cisplatin-based combination chemotherapy has become a standard of care for eligible patients based on the improved disease-specific and overall survival demonstrated in two randomized phase III trials, compared with surgery alone. For patients with disease downstaging to non-MIBC at the time of radical cystectomy as a result of neoadjuvant chemotherapy, outcomes are outstanding, with 5-year overall survival of 80–90%. Nevertheless, the inability to define before treatment the patients who will and those who will not achieve such a response has impeded the achievement of better outcomes for patients with MIBC. High-throughput DNA and RNA profiling technologies might help to overcome this barrier and enable a more-personalized approach to the use of cytotoxic neoadjuvant chemotherapy. In the past 2 years, trial results have demonstrated the unprecedented ability of immune- checkpoint blockade to induce durable remissions in patients with metastatic disease that has progressed after chemotherapy; studies are now urgently needed to determine how best to incorporate this powerful therapeutic modality into the care of patients with MIBC. Herein, we review the evolution of chemotherapy and immunotherapy for muscle-invasive bladder cancer.

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Acknowledgements

The work of S.A.F. and J.E.R. is supported, in part, by a NIH/National Cancer Institute (NCI) Cancer Center Support Grant (P30 CA008748).

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  1. Department of Medicine, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, 10065, New York, USA

    Samuel A. Funt & Jonathan E. Rosenberg

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Correspondence to Samuel A. Funt or Jonathan E. Rosenberg.

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S.A.F. declares stock ownership in Kite Pharma. J.E.R. has been a consultant for Agensys, Eli Lilly, Roche and Sanofi, and declares a patent interest in ERCC2 testing for cisplatin sensitivity.

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Funt, S., Rosenberg, J. Systemic, perioperative management of muscle-invasive bladder cancer and future horizons. Nat Rev Clin Oncol 14, 221–234 (2017). https://doi.org/10.1038/nrclinonc.2016.188

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