Division of Medical Oncology, Department of Internal Medicine, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, USA.
Division of Medical Oncology, Department of Medicine, University of Washington, Seattle Cancer Care Alliance, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
Cancer Treat Res Commun. 2021;27:100325. doi: 10.1016/j.ctarc.2021.100325. Epub 2021 Jan 28.
Metastatic bladder cancer has poor overall survival. Though systemic therapies have shown to improve overall survival, real-world studies have shown that more than half of the patients do not receive any systemic therapy, while only around 15-20% receive second-line therapy. Even in patients receiving systemic therapies a disproportionately higher use of carboplatin is observed in the first line despite proven superior effectiveness of cisplatin. Reasons for these observations include moderate effectiveness and relatively toxicity of platinum-based chemotherapy regimens, concerns with performance status and co-morbidities in this predominantly older patient population, communications barriers, lack of social support, and access to affordable healthcare. Herein we discuss potential ways to overcome these challenges which include (1) preventing/delaying metastatic disease by maximizing the receipt of neoadjuvant cisplatin-based therapy, and development of better tolerated and more effective neoadjuvant and adjuvant therapies, (2) use of avelumab maintenance therapy after 4-6 cycles of platinum-based chemotherapy to overcome attrition of patients from first to second-line therapy, (3) advancing effective and well-tolerated systemic therapies such as enfortumab vedotin, and erdafitinib to the first-line metastatic setting or even to the localized setting, (4) further development of effective and well-tolerated therapies like sacituzumab govitecan, a novel antibody-drug conjugate and (5) improving affordability and accessibility to systemic therapy agents.
转移性膀胱癌总体生存率较差。虽然系统治疗已被证明可提高总体生存率，但真实世界研究表明，超过一半的患者未接受任何系统治疗，而只有约 15-20%的患者接受二线治疗。即使在接受系统治疗的患者中，一线治疗中也观察到卡铂的使用不成比例地增加，尽管顺铂的疗效已被证实更优。出现这些观察结果的原因包括铂类化疗方案的疗效中等且毒性相对较大、在以老年人为主的这一患者群体中对体能状态和合并症的担忧、沟通障碍、缺乏社会支持以及获得负担得起的医疗保健的机会有限。在此，我们讨论了克服这些挑战的潜在方法，包括 (1) 通过最大限度地接受新辅助顺铂为基础的治疗来预防/延迟转移性疾病，并开发更好耐受和更有效的新辅助和辅助治疗，(2) 在铂类化疗 4-6 个周期后使用avelumab 维持治疗，以克服患者从一线治疗向二线治疗的流失，(3) 将有效且耐受良好的系统治疗方法，如 enfortumab vedotin 和 erdafitinib，推进到一线转移性环境，甚至局部环境，(4) 进一步开发有效且耐受良好的治疗方法，如 sacituzumab govitecan，一种新型抗体药物偶联物，(5) 提高系统治疗药物的可负担性和可及性。
