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Management of Advanced Urothelial Carcinoma in Older and Frail Patients: Have Novel Treatment Approaches Improved Their Care?

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Abstract

Patients with urothelial carcinoma tend to be older and frailer with a large number of chronic medical conditions. This is particularly pronounced in those with unresectable locally advanced and metastatic urothelial carcinoma. Prior to 2016, treatment options in advanced urothelial carcinoma were limited to chemotherapy, and as a result, a large number of patients were not receiving disease-directed management. Over the last 6 years, multiple alternative modalities including immune checkpoint inhibitors and targeted therapies have been introduced. They are being utilized clinically in older and frail patients, but there are limited studies investigating outcomes in these specific populations. Based upon current evidence, age does not impact the efficacy and tolerance of immune checkpoint inhibitors if patients are fit enough to receive therapy. In frailer patients, immune checkpoint inhibitors appear to be safe, but outcomes from largely retrospective studies demonstrate mixed data regarding their efficacy. Although there are indications from clinical trials that enfortumab vedotin, sacituzumab govitecan, and erdafitinib are also efficacious irrespective of age, there is still not enough evidence to draw definitive conclusions about their use in older and frail patients. Regardless, in all older patients with advanced urothelial carcinoma, it is critical to evaluate for frailty through geriatric screening tools and comprehensive assessments. Combining these evaluations with consideration of an individual patient’s goals should be the foundation upon which therapeutic decisions are made in this population of patients.

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Fig. 1

*Real-world analysis [9, 19, 20, 86, 94]

Fig. 2

**Includes the Galsky criteria, EORTC-GU Group criteria, and others [15, 33, 37, 61, 64, 65]

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Authors and Affiliations

  1. Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA

    Brian M. Russell & Leora Boussi

  2. Beth Israel Deaconess Medical Center and PSMAR-IMIM Lab, Harvard Medical School, 330 Brookline Avenue, Boston, MA, 02215, USA

    Joaquim Bellmunt

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  1. Brian M. Russell
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Joaquim Bellmunt has grants pending or has received grants from Pfizer, MSD, and Takeda. He has received consulting fees or honorarium from Merck, Genentech, Astra Zeneca, Pfizer, and MSD. He has stock or stock options in Rainer Therapeutics, and he receives royalties from UpToDate. Brain M. Russell and Leora Boussi have no relevant conflicts of interest.

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BMR drafted and wrote the manuscript with the assistance of JB and LB. All authors reviewed, revised, and contributed to the final manuscript. All authors approved the final manuscript prior to submission.

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Russell, B.M., Boussi, L. & Bellmunt, J. Management of Advanced Urothelial Carcinoma in Older and Frail Patients: Have Novel Treatment Approaches Improved Their Care?. Drugs Aging 39, 271–284 (2022). https://doi.org/10.1007/s40266-022-00933-2

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