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Defining cisplatin eligibility in patients with muscle-invasive bladder cancer

Abstract

The current treatment paradigm for muscle-invasive bladder cancer (MIBC) consists of cisplatin-based neoadjuvant chemotherapy followed by local definitive therapy, or local definitive therapy alone for cisplatin-ineligible patients. Given that MIBC has a high propensity for distant relapse and is a chemotherapy-sensitive disease, under-utilization of chemotherapy is associated with suboptimal cure rates. Cisplatin eligibility criteria are defined for patients with metastatic bladder cancer by the Galsky criteria, which include creatinine clearance ≥60 ml/min. However, consensus is still lacking regarding cisplatin eligibility criteria in the neoadjuvant, curative MIBC setting, which continues to represent a substantial barrier to the standardization of patient care and clinical trial design. Jiang and colleagues accordingly suggest an algorithm for assessing cisplatin eligibility in patients with MIBC. Instead of relying on an absolute renal function threshold, their algorithm emphasizes a multidisciplinary and patient-centred approach. They also propose mitigation strategies to minimize the risk of cisplatin-induced nephrotoxicity in selected patients with impaired renal function. This new framework is aimed at reducing the inappropriate exclusion of some patients from cisplatin-based neoadjuvant chemotherapy (which leads to under-treatment) and harmonizing clinical trial design, which could lead to improved overall outcomes in patients with MIBC.

Key points

  • Current heterogeneous definitions of adequate renal function for cisplatin-based chemotherapy might cause harm by inappropriately excluding patients from neoadjuvant chemotherapy, leading to under-treatment of muscle-invasive bladder cancer.

  • An absolute threshold of creatinine clearance (CrCl) ≥60 ml/min excludes up to 50% of patients with muscle-invasive bladder cancer from receiving cisplatin-based neoadjuvant chemotherapy and might be inappropriate for many patients.

  • Estimation of baseline renal function using the Chronic Kidney Disease–Epidemiology Collaboration equation is preferred for determining cisplatin eligibility, whereas CrCl is preferred to guide cisplatin dosing.

  • Selected patients with baseline CrCl 40–60 ml/min might be safely treated with cisplatin-based neoadjuvant chemotherapy provided that informed patient discussions, multidisciplinary input and appropriate mitigation strategies take place.

  • Further research is urgently needed to fully define the risk of nephrotoxicity from cisplatin-based neoadjuvant chemotherapy and derive optimal dosing and mitigation strategies to improve the outcomes of muscle-invasive bladder cancer.

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Fig. 1: Overlapping renal function thresholds in current clinical trials in muscle-invasive bladder cancer.
Fig. 2: Proposed algorithm for determining eligibility for neoadjuvant cisplatin-based chemotherapy in patients with MIBC.

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D.M.J. researched data for the article and wrote the first draft. All authors contributed substantially to discussion of its content and participated in review and/or editing of the manuscript before submission.

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Correspondence to Srikala S. Sridhar.

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D.M.J declares that she has received consulting fees from Bayer. N.S.A. declares that she has acted as a consultant and/or advisor for Astellas, AstraZeneca, Janssen, Merck, Pfizer and Sanofi. S.S.S. declares that she has acted as a consultant and/or advisor for AstraZeneca, Janssen, Merck, Roche and Sanofi. S.G., A.K., A.M.-M., S.A.N. and N.B. declare no competing interests.

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Nature Reviews Urology thanks Y. Loriot, S. Culine and A. Balar for their contribution to the peer review of this work.

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Related links

American Society of Nephrology Onco-Nephrology curriculum: https://www.asn-online.org/education/distancelearning/curricula/onco/

National Kidney Foundation GFR calculator: https://www.kidney.org/professionals/kdoqi/gfr_calculator

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Jiang, D.M., Gupta, S., Kitchlu, A. et al. Defining cisplatin eligibility in patients with muscle-invasive bladder cancer. Nat Rev Urol 18, 104–114 (2021). https://doi.org/10.1038/s41585-020-00404-6

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