Emerging perioperative therapeutic approaches in muscle invasive bladder cancer

Bladder cancer is a significant healthcare burden with more than 17,000 deaths in the United States in 2018. Patients who are diagnosed with muscle invasive bladder cancer (MIBC) have a high rate of micro-metastatic disease and have a much poorer prognosis compared with patients who have less advanced lesions. Historically, neoadjuvant administration of cisplatin-based therapy followed by surgery has been the mainstay of treatment. Unfortunately, of patients who come in with initially diagnosed MIBC, more than 50% are ineligible for traditional cisplatin-based therapy. Today, new modalities of treatment such as immune checkpoint inhibitors are beginning to radically improve outcomes in this population. The addition of immune checkpoint therapy to traditional chemotherapy appears to augment pathologic complete response rates in the bladder during surgery. Immunotherapy combinations also provide novel trimodality approaches with excellent outcomes in those pursuing non-surgical management. Pure immunotherapy approaches appear promising in the neoadjuvant and adjuvant setting, and the immune checkpoint inhibitor nivolumab is now approved in the adjuvant setting for high-risk patients. Antibody drug conjugates, such as enfortumab vedotin, and targeted therapies, such as infigratinib, are in trials in the perioperative setting. This review article summarizes the current evidence and likely future developments for the management of muscle invasive bladder cancer in 2022 and beyond.