Emerging targeted therapies in advanced bladder cancer

Urothelial bladder cancer (UBC) is the ninth most common cancer worldwide, as over 300,000 people are diagnosed every year, with an annual death of at least 120,000 people (1). Approximately 70% of bladder cancers are of the non-muscle invasive type, which has a favorable prognosis of 85% 5-year survival rate. However, the other 30% are invasive or metastatic, which have poor prognoses and a high tendency of recurrence and distant metastasis (2-4). Currently, the standard therapy for recurrent or metastatic UBC is platinum-based chemotherapy (4,5). However, the clinical outcome of standard chemotherapy is disappointing, with the 5-year survival rate being only approximately 10% (6). Moreover, only approximately 40% of patients respond to platinum-based chemotherapy, and for those who do not respond or have progressed after chemotherapy, the median survival time is only 9 months (7). As such, a novel approach is necessary to overcome this therapeutic challenge in treating advanced UBC. Moreover, as the median age of diagnosis of UBC is 65 years, presence of comorbidities, such as renal impairment, makes more than a third of advanced UBC patients ineligible for the standard cytotoxic chemotherapy (8,9). In order to resolve these limitations, various molecular targeting agents are currently being investigated. The most notable have been the immune checkpoint inhibitors (ICI), which include the anti-PD-L1 antibody, atezolizumab, that has been approved by the Food and Drug Administration (FDA) as a second-line therapy for UBC (10,11). This achievement has dramatically advanced the treatment outcome of advanced UBC. This review paper aims to provide insights on the currently available and promising systemic targeted therapies in UBC