Temporal Effect on PD-L1 Detection and Novel Insights Into Its Clinical Implications in Non-Small Cell Lung Cancer.

Objectives: Several studies rely on archived tissue blocks to assess the PD-L1 scores; however, a detailed analysis of potential variations of scores between fresh and archived tissue blocks still lacks. In addition, the prognostic implications of PD-L1 in lung cancers have not yet been completely understood. Here, we aimed to investigate the temporal variation in PD-L1 scores from clinical samples and the clinical implications of PD-L1 in non-small cell lung cancer (NSCLC).

Methods: NSCLC cases from January 2005 to June 2023 were considered for this study, and PD-L1 scores in archived and fresh tissue blocks were analyzed. Association of PD-L1 with various driver mutations was explored, and implications of PD-L1 in progression-free survival (PFS) and overall survival (OS) were analyzed.

Results: Our study revealed a significant disparity in PD-L1 scores between archived and fresh tissue blocks, and a temporal variation in scores within 6 months of tissue acquisition. Advanced-stage primary tumors, metastatic lymph nodes, and visceral pleural invasion revealed higher PD-L1 expression as presented by tumor proportion score (TPS). Notably, in fully resected stage I/II NSCLC cases, OS was better in the high PD-L1 (≥ 50% TPS) cohort with driver mutations compared to cases without driver mutations (hazard ratio-0.5129, 95% confidence interval 0.2058-1.084, p = 0.0779). In contrast, high PD-L1 was associated with worse OS compared to no PD-L1 (< 1% TPS) (hazard ratio-2.431, 95% confidence interval 1.144-6.656, p = 0.0242) in the cohort without driver mutations. Furthermore, the presence of a KRAS mutation favored the outcome of anti-PD-L1/PD1 immunotherapy in advanced NSCLC.

Conclusion: PD-L1 detection from tissue blocks was found to vary temporally, urging for a prioritized consideration for patients with marginal scores when archived blocks are employed for its detection. Prognostic roles of PD-L1 were associated with driver mutations, and KRAS mutations favored the outcome of anti-PD-L1/PD1 therapy in advanced NSCLC.