Muscle invasive bladder cancer: where is the field headed?

Introduction: 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. Areas covered: 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. Expert opinion: 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.