Precision Oncology in Urothelial Cancer

Bladder cancer (BCa) is the fifth-most common cancer in the US with only a 50% 5-year survival for patients whose cancer invades the muscle of the bladder (Stage II or muscle-invasive bladder cancer, MIBC). Despite multimodal treatment, recurrence and progression can occur both locally in the pelvis or with metastasis throughout the body. Therefore, the current standard of care for MIBC involves the “neoadjuvant paradigm”, with patients treated with systemic therapy before bladder removal. Unfortunately, less than 20% of MIBCs will be treated and benefit from NAC with 50% of patients NAC-ineligible due to medical comorbidities  and the remaining MIBCs treated with NAC (30% overall) resistant to chemotherapy. Thus, only 20% of patients with MIBC are treated and derive a benefit from the current standard of care therapy with NAC. The remainder of patients are exposed to toxicity and a delay in definitive surgery. As an alternative to NAC, several recent phase II trials have tested the safety and tolerability of immunotherapy instead of NAC before surgery. With less toxicity, and a tumor response rate exceeding those achieved with NAC, immunotherapy with antibodies targeting PD1/PDL1 and CTLA-4 have less side-effects and are not dependent on renal function. Thus, there may soon be a need to choose the “best” systemic therapy (either chemotherapy or immunotherapy) for each patient, prior to surgery.