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Contemporary update on neoadjuvant therapy for bladder cancer

  • Review Article
  • Published:

From Nature Reviews Urology

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Key Points

  • Level 1 evidence supports the use of neoadjuvant chemotherapy preceding radical cystectomy in patients with bladder cancer

  • Poor accrual, selection bias and quality of surgery were probably confounding factors in previous randomized trials evaluating neoadjuvant chemotherapy

  • The survival benefit associated with neoadjuvant chemotherapy is modest and a risk of overtreatment with its associated adverse effects exists

  • Novel therapies might alter the current neoadjuvant paradigm; immune checkpoint inhibitors represent the most promising class of targeted agents in this setting

  • In the future, genomic characterization of bladder cancer tumours before treatment might improve prediction of individual response to drug therapy and aid in patient selection

Abstract

Administration of neoadjuvant chemotherapy preceding radical cystectomy in patients with bladder cancer remains a matter of debate. Results of prospective, randomized studies have demonstrated an overall absolute survival benefit of 5% at 5 years, provided cisplatin-based combination regimens are used. Owing to the perception of a modest survival benefit, the medical community has been slow to adopt the use of neoadjuvant chemotherapy. Other reasons for the underuse of neoadjuvant chemotherapy range from patient ineligibility to fear of delaying potentially curative surgery in nonresponders. Instead, several institutions have adopted an individualized, risk-adapted approach, in which the decision to administer chemotherapy is based on clinical stage and patient comorbidity profile. The development of new cytotoxic and targeted therapies, in particular immune checkpoint inhibitors, warrants well-designed prospective studies to test their efficacy alone or in combination in the neoadjuvant setting. Moving forward, genomic characterization of muscle-invasive bladder cancer could offer information that aids clinicians in selecting the appropriate chemotherapy regimen. Following neoadjuvant therapy, every effort should be made to ensure optimal surgery, as surgical margins and the number of removed lymph nodes are prognostic factors; thus, radical cystectomy and a meticulous extended pelvic lymph node dissection should be performed by expert surgeons.

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Figure 1: Postulated mechanisms of action of PD-1, PD-L1 and PD-L2.
Figure 2: Schematic representation of intrinsic subtypes of bladder cancer143.

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  1. Department of Urology, Inselspital, Bern University Hospital, University of Bern, Bern, CH-3010, Switzerland

    Daniel P. Nguyen & George N. Thalmann

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D.P.N. researched data for the article and wrote the manuscript. Both authors made a substantial contribution to discussion of the article's content and reviewed and/or edited the manuscript before submission.

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Correspondence to Daniel P. Nguyen.

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Nguyen, D., Thalmann, G. Contemporary update on neoadjuvant therapy for bladder cancer. Nat Rev Urol 14, 348–358 (2017). https://doi.org/10.1038/nrurol.2017.30

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