INTRODUCTION: Treatment strategy for inoperable and metastatic urothelial 
carcinoma (mUC) has been revolutionized by the introduction of programmed cell 
death protein 1 (PD-1) and programmed cell death protein ligand (PD-L1) 
antibodies. During the last 3 decades treatment options were limited to 
chemotherapy, making further treatment of patients whose disease progressed 
under ongoing therapy or who were ineligible to receive cytotoxic therapy in the 
first place, nearly impossible.
EVIDENCE ACQUISITION: Five antibodies including pembrolizumab (PD-L1 antibody), 
atezolizumab (PD-1 antibody), nivolumab (PD-1 antibody), avelumab and durvalumab 
(PD-L1 antibodies) have been approved in the treatment of advanced urothelial 
carcinoma in first- and second-line treatment setting. The objective of this 
review was to examine and compare the different cohorts and to discuss the 
quality of the respective studies in order to set up selection criteria for 
clinical decision making.
EVIDENCE SYNTHESIS: So far pembrolizumab and atezolizumab have demonstrated 
overall survival (OS) benefit in phase II studies and have shown superiority 
over standard chemotherapy in phase III studies which has granted them approval 
in first and second-line treatment setting. Improved OS and durable responses 
were also seen in phase Ib/II non-randomized, single-arm trials conducted with 
nivolumab, avelumab and durvalumab and granting accelerated approval for 
second-line treatment. The huge advantage of immunotherapy and one of the 
reasons for its overall recognition is its good tolerability profile especially 
in comparison to chemotherapy.
CONCLUSIONS: Pembrolizumab has to be recommended in second-line therapy due to 
reporting in a phase III trial and OS survival benefit compared to chemotherapy 
control group. In cisplatin-eligible and treatment-naïve patients with visceral 
or liver metastases data also slightly favors pembrolizumab rather than 
atezolizumab.