Perioperative Immunotherapy in Muscle-Invasive Bladder Cancer

• Published in: Current treatment options in oncology 2023-09, Vol.24 (9), p.1213-1230
• Main Authors: Singh, Amisha, Osbourne, Appledene S., Koshkin, Vadim S.
• Format: Article
• Language: English
• Subjects: Biomarkers; Bladder cancer; Cancer therapies; Chemotherapy; Cisplatin; Clinical trials; Immune checkpoint inhibitors; Immunosuppressive agents; Immunotherapy; Invasiveness; Medicine; Medicine & Public Health; Oncology; Patients; Survival; Topical Collection on Genitourinary Cancers; Toxicity
• ISSN: 1527-2729; 1534-6277; 1534-5277
• DOI: 10.1007/s11864-023-01113-z

Opinion Statement There is an acute unmet need to develop novel treatment regimens in the perioperative setting since many patients with muscle-invasive bladder cancer (MIBC) are not eligible for the current standard of care (SOC) neoadjuvant treatment with cisplatin-based chemotherapy. The introduction of immune checkpoint inhibitors (ICIs), both as monotherapy and in combination regimens with other ICIs, chemotherapy, or targeted drugs, may provide safe and clinically effective treatment options that could revolutionize current standard of care. In the neoadjuvant setting, compelling data from phase II clinical trials suggests that single-agent immunotherapy, as well as dual-checkpoint blockade, may emerge as reasonable alternatives to traditional cisplatin-based chemotherapy. Prospective studies combining ICIs with chemotherapy or with antibody-drug conjugates have also demonstrated robust outcomes. However, these studies are not yet practice changing and data from larger randomized studies are needed to confirm this benefit. In the adjuvant setting, nivolumab is the FDA-approved treatment based on a disease-free survival benefit relative to placebo in a randomized trial. However, it will be important to confirm an overall survival benefit of this treatment and to better identify patients who need additional adjuvant treatment based on novel biomarker data. The treatment of muscle-invasive bladder cancer is moving toward the individualization of treatment options based on specific tumor and patient characteristics and away from the one-size-fits-all approach that has dominated this space for the last couple of decades. Emerging biomarker data, such as with ctDNA, suggests that immunotherapy may confer greater benefit to selected patients. Identifying who those patients are will be of paramount importance since additional treatments always come with additional toxicities. On the other hand, the more favorable toxicity profiles of certain immunotherapy-based regimens may make them superior options for some patients who would otherwise be unable to tolerate other systemic regimens. In the near future, it is likely that subsets of patients with MIBC will be receiving treatments with predominantly immunotherapy-based regimens while many patients may still be treated with regimens containing a cisplatin-based chemotherapy backbone. Currently ongoing clinical trials will help to better define patient populations optimized for each treatment.