Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria.
Department of Urology, University of Verona, Azienda Ospedaliera Universitaria Integrata, Verona, Italy.
Expert Opin Pharmacother. 2023 Feb;24(2):177-195. doi: 10.1080/14656566.2022.2150966. Epub 2022 Nov 29.
Despite recent developments in the landscape of urothelial carcinoma (UC) treatment, platinum combination chemotherapy still remains a milestone. Recently immunotherapeutic agents have gained ever-growing attractivity, particularly in the metastatic setting. Novel chemotherapeutic strategies and agents, such as antibody-drug conjugates (ADCs), and powerful combination regimens have been developed to overcome the resistance of most UC to current therapies.
Herein, we review the current standard-of-care chemotherapy, the development of ADCs, the rationale for combining therapy regimens with chemotherapy in current trials, and future directions in UC management.
Immunotherapy has prompted a revolution in the treatment paradigm of UC. However, only a few patients experience a long-term response when treated with single-agent immunotherapies. Combination treatments are necessary to bypass resistance mechanisms and broaden the clinical utility of current options. Current evidence supports the intensification of standard-of-care chemotherapy with maintenance immunotherapy. However, the optimal sequence, combination, and duration must be determined to achieve individual longevity with acceptable health-related quality of life. In that regard, ADCs appear as a promising alternative for single and combination strategies in UC, as they specifically target the tumor cells, thereby, theoretically improving treatment efficacy and avoiding extensive off-target toxicities.
尽管尿路上皮癌（UC）治疗领域最近取得了进展，但铂类联合化疗仍然是一个里程碑。最近，免疫治疗药物越来越受到关注，特别是在转移性环境中。为了克服大多数 UC 对现有疗法的耐药性，已经开发出了新型化疗策略和药物，如抗体药物偶联物（ADC），以及强大的联合治疗方案。
本文综述了当前的标准治疗化疗、ADC 的发展、在当前试验中将联合治疗方案与化疗相结合的原理，以及 UC 管理的未来方向。
免疫疗法促使 UC 的治疗模式发生了革命性变化。然而，只有少数患者在接受单药免疫治疗时能获得长期缓解。联合治疗是必要的，以克服耐药机制并扩大现有选择的临床应用。目前的证据支持在标准治疗化疗的基础上加强维持性免疫治疗。然而，必须确定最佳的顺序、组合和持续时间，以实现个体的长寿和可接受的健康相关生活质量。在这方面，ADC 作为 UC 中单一和联合策略的一种有前途的选择，因为它们可以特异性地靶向肿瘤细胞，从而理论上提高治疗效果并避免广泛的脱靶毒性。
