Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA.
Beth Israel Deaconess Medical Center and PSMAR-IMIM Lab, Harvard Medical School, 330 Brookline Avenue, Boston, MA, 02215, USA.
Drugs Aging. 2022 Apr;39(4):271-284. doi: 10.1007/s40266-022-00933-2. Epub 2022 Mar 28.
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.
患有尿路上皮癌的患者往往年龄较大且身体虚弱，并伴有大量慢性疾病。对于那些无法切除的局部晚期和转移性尿路上皮癌患者，这种情况更为明显。在 2016 年之前，晚期尿路上皮癌的治疗选择仅限于化疗，因此，许多患者并未接受针对疾病的治疗。在过去的 6 年中，已经引入了多种替代治疗方法，包括免疫检查点抑制剂和靶向治疗药物。这些方法正在为老年和体弱患者进行临床应用，但针对这些特定人群的研究结果有限。根据目前的证据，如果患者身体状况适合接受治疗，那么年龄不会影响免疫检查点抑制剂的疗效和耐受性。在身体更虚弱的患者中，免疫检查点抑制剂似乎是安全的，但来自大量回顾性研究的数据显示，其疗效存在差异。尽管临床试验表明，enfortumab vedotin、sacituzumab govitecan 和 erdafitinib 无论年龄大小均有效，但仍缺乏足够的证据来对这些药物在老年和体弱患者中的应用得出明确结论。无论如何，对于所有患有晚期尿路上皮癌的老年患者，通过老年综合评估和全面评估来评估虚弱情况至关重要。将这些评估与个体患者的目标相结合，应该成为该患者群体治疗决策的基础。
