Targeting the Immune Checkpoint in Bladder Cancer

The introduction of immune checkpoint inhibitors (ICIs) has revolutionized the therapeutic landscape of urothelial cancer (UC). Many treatment approaches in different settings are being investigated to harness the immune system. Novel combination strategies are emerging with promising results, offering potential synergistic effects and improved treatment outcomes. However, challenges persist, particularly regarding identifying patients who most benefit from these therapeutic strategies. While some patients experience significant improvements in response and survival, the clinical benefit remains uncertain in some scenarios. In this context, tumor-associated biomarkers hold promise in guiding personalized treatment approaches. By analyzing different biomarkers such as genomic profiles, tumor mutational burden, mutation spectrum, and tumor-associated biomarkers such as PD-1/PD-L1 expression, several groups have tried to stratify patients based on their likelihood of responding to immunotherapy. Moreover, the emergence of liquid biomarkers offers unprecedented opportunities for real-time monitoring of treatment response and disease progression. However, the lack of standardization and the presence of conflicting results in biomarker assessments pose significant challenges. Further prospective trials are warranted to identify reliable biomarkers, and standardization of methodology is necessary to ensure its consistency and accuracy. This chapter explores various facets of immunotherapy in UC, shedding light on the current therapeutic targets within the immune-checkpoint cascade, tumor-associated biomarkers either tissue- or liquid-based. Additionally, we present the emerging data on immunotherapy strategies’ efficacy in UC with variant histologies. Lastly, we explore novel immunotherapy combinations, such as IO-FGFRi and IO-ADCs.