Immune Checkpoint Inhibitors in Urothelial Carcinoma: Recommendations for Practical Approaches to PD-L1 and Other...

Area of Science:

• Oncology
• Immunology
• Pathology
• Biomarker Development

Background:

• Immuno-oncology (IO) agents targeting programmed cell death 1 (PD-1) and programmed cell death-ligand 1 (PD-L1) are established treatments for metastatic urothelial carcinoma (UC).
• PD-L1 expression is a key biomarker for predicting patient response to IO therapy in UC.
• Current PD-L1 assays exhibit variability in antibodies, protocols, cutoffs, and scoring, necessitating standardization for reliable clinical application.

Purpose of the Study:

• To assess the current landscape and perspectives on biomarker-guided patient selection for anti-PD-1/PD-L1 therapy in UC.
• To develop evidence-based recommendations for best practices in PD-L1 testing for UC.
• To foster improved communication between clinicians and pathologists for timely and accurate PD-L1 assay results.

Main Methods:

• Convened three international workshops (Italy, Malaysia, Spain) from December 2018 to December 2019.
• Gathered input from experienced pathologists and oncologists globally on PD-L1 testing in UC.
• Developed a standardized test request form to facilitate clinician-pathologist communication.

Main Results:

• Identified significant variability in current PD-L1 assay methodologies and interpretation across different institutions.
• Formulated recommendations for best practices in PD-L1 testing, interpretation, and reporting for UC.
• Emphasized the need for robust pre-analytical and analytical standards to ensure high-quality PD-L1 results.

Conclusions:

• Standardized PD-L1 testing is essential for optimizing patient selection for IO therapies in metastatic UC.
• The developed recommendations and test request form aim to improve the consistency and reliability of PD-L1 biomarker assessment.
• Ongoing evaluation of novel biomarkers for IO agents in UC is crucial for advancing personalized medicine.