Impact of Specimen Characteristics on PD-L1 Testing in Non-Small Cell Lung Cancer: Validation of the IASLC PD-L1 Testing Guidelines

Abstract Introduction Molecules targeting the Programmed Death Receptor-1 or its ligand (PD-L1) revolutionized the treatment of patients with non-small cell lung carcinoma (NSCLC). The only approved biomarker for predicting treatment response is the PD-L1 tumor proportion score (TPS) determined by immunohistochemistry. According to IASLC recommendations, specimens with fewer than 100 tumor cells or that are older than three years should not be used for PD-L1 testing and the reliability of cell blocks has yet to be validated. Methods This retrospective study included 1249 consecutive patients with NSCLC that were tested for PD-L1 (22C3) between September 2016 and April 2017. The associations between the presence of suboptimal characteristics (specimens with fewer than 100 tumor cells, older than three years, or cell blocks) and PD-L1 TPS were examined using a multinomial logistic regression. Results Specimens from 35.5% of patients had at least one suboptimal characteristic. For patients with a PD-L1 TPS of higher than 50%, there was a significantly higher probability that they had a specimen with more than 100 tumor cells (OR=1.97, p=0.008) and a more recent block (within 30 days versus more than three years, OR=2.46, p=0.023). There was no statistical difference in PD-L1 TPS between cell blocks and tissue specimens (biopsy OR=0.99, p=0.996, surgery OR=0.73, p=0.302). Conclusion Our results suggest that specimens containing fewer than 100 tumor cells or that are older than three years may lead to an underestimation of the PD-L1 status. Our findings also provide support for the use of cell blocks for PD-L1 testing, although further research is needed.