Potential for companion diagnostic use and inter-rater agreement of programmed death ligand-1 (PD-L1) clone 22C3 expression scores in colorectal cancer

Abstract Background Expression of programmed death ligand-1 (PD-L1) guide use of immune checkpoint inhibitors (ICI) in several cancers. In colorectal cancer (CRC), ICI is only approved for metastatic CRC, while data suggest high efficacy in operable CRC. The aim of this study was to investigate the inter-rater agreement of PD-L1 as a companion diagnostic marker. Methods Specimen (n = 166 tumors) stained by PD-L1 22C3 clone were scored by pathologists in pairs for tumor proportion score (TPS), combined positive score (CPS) and immune cell score (IC) using 3 different agreement coefficients. Results Raw scores of the two pathologists had ‘good’ to ‘excellent’ correlation. Spearman’s rho for TPS = 0.917 (95%CI 0.839–0.995), for CPS = 0.776 (95%CI 0.726–0.826) and IC = 0.818 (95%CI 0.761–0.875). Kappa (κ)-agreements of ≥ 1% and ≥ 10% cutoffs had excellent correlation for TPS. For CPS ≥ 1% and ≥ 10%, the κ = 0.32 (95%CI 0.12–0.51) and κ = 0.36 (95%CI 0.25–0.48), respectively. For IC ≥ 1% and ≥ 10%, the κ = 0.53 (95%CI 0.18–0.79) and κ = 0.61 (95%CI 0.48–0.73), respectively. Gwen’s agreement coefficient (AC 1 ) showed higher agreement coefficients than κ-values for most, but not all cut-offs. Conclusion Agreement was for PD-L1 was good to excellent for raw scores. Agreement variation suggests need for more robust criteria for PD-L1 as a companion diagnostic marker.