20.500.12556/DKUM-100352 Limited predictive value of PD-L1 TPS for pathological response in NSCLC is not attributable to interobserver variability Background PD-L1 tumor proportion score (TPS) is used to guide immunotherapy in non-small cell lung cancer (NSCLC), yet its ability to predict pathological response in the neoadjuvant setting remains limited. Methods Thirty pathologists from 11 countries independently assessed PD-L1 TPS in pre-treatment biopsies and residual viable tumor (RVT) in matched resection specimens after neoadjuvant chemoimmunotherapy in 30 digitized cases from the ReGraDE (regression grading in Germany) study. Interobserver agreement was evaluated using intraclass correlation coefficients (ICC) and Fleiss’ kappa. Associations between TPS and RVT were analyzed using Pearson correlation, and correlations derived from single-rater and averaged TPS were compared using the Williams test. Results Interobserver agreement was moderate for both TPS and RVT (ICC = 0.74, 95% CI 0.60–0.87, and ICC = 0.74, 95% CI 0.62–0.85, respectively) and became near-perfect when mean scores per case were calculated across observers (ICC = 0.99, for both). However, TPS remained poorly correlated with RVT for both single-rater assessment (r = –0.17, p = 0.38) and averaged TPS (r = –0.16, p = 0.39) with no significant difference between these approaches (p = 0.96). Differences in interpretation thresholds were observed particularly in borderline cases around the 1% TPS cut-off and in distinguishing 0% from minimal RVT, but did not account for the lack of association between TPS and RVT. Systematic differences were observed depending on individual professional experience, particularly in borderline cases. Conclusion Interobserver variability does not explain the limited predictive value of PD-L1 TPS in the neoadjuvant setting, suggesting an intrinsic limitation of the biomarker. non-small cell lung cancer (NSCLC) PD-L1 tumor proportion score (TPS) residual viable tumor (RVT) neoadjuvant chemoimmunotherapy interobserver variability true true true Elsevier Angleški jezik Angleški jezik Znanstveno delo 2026-09-15 03:06:00 2026-09-15 11:03:05 2026-09-16 03:11:26 0000-00-00 00:00:00 2026 0 0 str. [1]-8 Aug. 2026, št. članka 109510 Letn. 218 Aug. 2026 0000-00-00 Zaloznikova Objavljeno NiDoloceno 2026-06-05 2026-05-05 2026-08-01 616-006 291043075 10.1016/j.lungcan.2026.109510 1872-8332 RAZ_Steinestel_Konrad_2026.pdf RAZ_Steinestel_Konrad_2026.pdf 1 3A1E7F3368F695B3A2BCC5AEEC798C93 dc83d18e602e882a9c6e90a5a39019016e3a9447e40e57ee95c4a560522a9796 0108a98e-b0e4-11f1-9175-00155d0001be https://dk.um.si/Dokument.php?lang=slv&id=212468 https://doi.org/10.1016/j.lungcan.2026.109510 0 2210119c-b0e4-11f1-9175-00155d0001be https://dk.um.si/Dokument.php?lang=slv&id=212469 https://linkinghub.elsevier.com/retrieve/pii/S0169500226005714 1 9ec6e5d3-b0a1-11f1-9175-00155d0001be https://dk.um.si/Dokument.php?lang=slv&id=212415 Medicinska fakulteta 0 0 0