Inter- and Intra-Observer Agreement of PD-L1 SP142 Scoring in Breast Carcinoma-A Large Multi-Institutional International Study

Simple Summary PD-L1 analysis in TNBC is essential for selecting patients eligible for immunotherapy. Limited data are available on pathologists' concordance regarding PD-L1 assessment. Twelve pathologists of various expertise from three European countries digitally analysed 100 breast cancer core biopsies stained using the SP142 PD-L1 assay in two rounds. The overall inter-observer agreement among the pathologists was substantial. The intra-observer agreement was substantial to almost perfect. The expert scorers were more concordant in evaluating staining percentage compared with those of the non-experts. Challenging cases around the 1% cut-off value for positivity were identified and represented a small 6-8%) proportion of all cases. The experts were more concordant in scoring those cases. The study shows reassuringly strong inter- and intra-observer concordance among pathologists in PD-L1 scoring. A proportion of low-expressors remain challenging to assess, and these would benefit from addressing the technical issues, testing a different sample and/or referring for expert opinions. The assessment of PD-L1 expression in TNBC is a prerequisite for selecting patients for immunotherapy. The accurate assessment of PD-L1 is pivotal, but the data suggest poor reproducibility. A total of 100 core biopsies were stained using the VENTANA Roche SP142 assay, scanned and scored by 12 pathologists. Absolute agreement, consensus scoring, Cohen's Kappa and intraclass correlation coefficient (ICC) were assessed. A second scoring round after a washout period to assess intra-observer agreement was carried out. Absolute agreement occurred in 52% and 60% of cases in the first and second round, respectively. Overall agreement was substantial (Kappa 0.654-0.655) and higher for expert pathologists, particularly on scoring TNBC (6.00 vs. 0.568 in the second round). The intra-observer agreement was substantial to almost perfect (Kappa: 0.667-0.956), regardless of PD-L1 scoring experience. The expert scorers were more concordant in evaluating staining percentage compared with the non-experienced scorers (R-2 = 0.920 vs. 0.890). Discordance predominantly occurred in low-expressing cases around the 1% value. Some technical reasons contributed to the discordance. The study shows reassuringly strong inter- and intra-observer concordance among pathologists in PD-L1 scoring. A proportion of low-expressors remain challenging to assess, and these would benefit from addressing the technical issues, testing a different sample and/or referring for expert opinions.