Department of Hematology/Oncology, Fox Chase Cancer Center, Philadelphia, PA, USA.
Department of Hematology/Oncology, AdventHealth Cancer Institute and the University of Central Florida, Orlando, FL, USA.
Expert Opin Biol Ther. 2023 Jul-Dec;23(9):913-927. doi: 10.1080/14712598.2023.2238607. Epub 2023 Jul 21.
The standard treatment for muscle-invasive bladder cancer (MIBC) is cisplatin-based neoadjuvant chemotherapy (NAC) followed by radical cystectomy or upfront radical cystectomy for cisplatin-ineligible patients. In those who are ineligible for or refuse radical cystectomy, trimodal therapy with chemoradiation is offered. However, with the success of immune checkpoint inhibitors (ICI) and antibody-drug conjugates such as enfortumab vedotin in the metastatic setting, several trials are implementing these drugs in the neoadjuvant setting for cisplatin ineligible patients. Indeed, nivolumab is approved as adjuvant therapy for high-risk muscle-invasive urothelial carcinoma.
Clinical trials using ICI, ICI/ICI, and ICI/chemotherapy combination therapies in the perioperative setting have been completed. These clinical trials have demonstrated that neoadjuvant ICI are safe and have encouraging pCR, making them promising treatment options. Neoadjuvant enfortumab vedotin alone and in combination with pembrolizumab is also being studied, and preliminarily to have promising activity. ICI is also being combined with radiation therapy (RT) and early data indicate that ICI combined with RT or chemo-RT may be safe with promising activity.
Biomarkers are urgently needed to identify appropriate treatment options for individual patients. The use of novel treatment approaches and biomarkers will help shape the future of precision therapy for MIBC and enable bladder preservation.
肌层浸润性膀胱癌(MIBC)的标准治疗方法是顺铂为基础的新辅助化疗(NAC),然后对顺铂不耐受的患者进行根治性膀胱切除术或 upfront 根治性膀胱切除术。对于不适合或拒绝根治性膀胱切除术的患者,提供三联疗法(放化疗)。然而,免疫检查点抑制剂(ICI)和抗体药物偶联物(如 enfortumab vedotin)在转移性环境中的成功,促使多项试验将这些药物应用于顺铂不耐受患者的新辅助环境中。事实上,nivolumab 已被批准用于高危肌层浸润性尿路上皮癌的辅助治疗。
已完成了在围手术期使用 ICI、ICI/ICI 和 ICI/化疗联合治疗方案的临床试验。这些临床试验表明,新辅助 ICI 是安全的,并且具有令人鼓舞的 pCR,这使它们成为很有前途的治疗选择。单独使用 enfortumab vedotin 以及与 pembrolizumab 联合使用也在研究中,初步结果显示具有很有前途的活性。ICI 也与放射治疗(RT)联合使用,早期数据表明 ICI 联合 RT 或 chemo-RT 可能是安全的,并且具有很有前途的活性。
迫切需要生物标志物来为个体患者确定合适的治疗选择。新型治疗方法和生物标志物的使用将有助于为 MIBC 的精准治疗塑造未来,并实现膀胱保留。