Immune Checkpoint Inhibitors in Urothelial Carcinoma: Recommendations for Practical Approaches to PD-L1 and Other Potential Predictive Biomarker Testing

Simple Summary The predominant histologic type of bladder cancer is urothelial carcinoma (UC). Programmed cell death-ligand 1 (PD-L1) expression levels in UC tumors help clinicians determine which patients are more likely to respond to immuno-oncology (IO) therapies; as such, the harmonization of PD-L1 testing in evaluating patients is increasingly important. A series of international workshops, involving renowned pathologists and oncologists, were held to develop best practice approaches to PD-L1 testing in UC. It was agreed that robust control of analytical standards is required to obtain quality PD-L1 results and that interpretation and reporting of PD-L1 require clear inter-clinician communication. Recommendations for the best practices for PD-L1 testing in UC are provided. A PD-L1 test request form for pathology laboratories was also developed and included here, encouraging communication between clinicians and pathologists, and ensuring fast and high-quality test results. Novel biomarkers being evaluated for immuno-oncology agents in UC are also briefly discussed. Immuno-oncology (IO) agents (anti-programmed cell death 1 (PD-1) and anti-programmed cell death-ligand 1 (PD-L1)) are approved as first- and second-line treatments for metastatic UC. PD-L1 expression levels in UC tumors help clinicians determine which patients are more likely to respond to IO therapies. Assays for approved IO agents use different antibodies, immunohistochemical protocols, cutoffs (defining "high" vs. "low" PD-L1 expression), and scoring algorithms. The robust control of pre-analytical and analytical standards is needed to obtain high-quality PD-L1 results. To better understand the status and perspectives of biomarker-guided patient selection for anti-PD-1 and anti-PD-L1 agents in UC, three workshops were held from December 2018 to December 2019 in Italy, Malaysia, and Spain. The primary goal was to develop recommendations for best practice approaches to PD-L1 testing in UC. Recommendations pertaining to the interpretation and reporting of the results of PD-L1 assays from experienced pathologists and oncologists from around the globe are included. A test request form for pathology laboratories was developed as a critical first step for oncologists/urologists to encourage communication between clinicians and pathologists, ensuring fast and high-quality test results. In this era of personalized medicine, we briefly discuss novel biomarkers being evaluated for IO agents in UC.