Immune checkpoint inhibitors in urothelial carcinoma: Recommendations for practical approaches to pd-l1 and other potential predictive biomarker testing

Abstract

Immuno-oncology (IO) agents (anti–programmed cell death 1 (PD-1) and anti–pro-grammed cell death-ligand 1 (PD-L1)) are approved as first-and second-line treatments for meta-static 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, immuno-histochemical protocols, cutoffs (defining “high” vs. “low” PD-L1 expression), and scoring algo-rithms. The robust control of pre-analytical and analytical standards is needed to obtain high-qual-ity 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 on-cologists 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.