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

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.