Comparative study of the PD-L1 status between PET/CT-guided biopsies and matched surgical specimens of non-small cell lung cancer

Introduction: PD-L1 expression status is important for screening appropriate patients to use anti-PD-1/PD-L1 therapies. For example, Pembrolizumab was approved for the first-line treatment of patients with metastatic non-small cell lung cancer (NSCLC) whose PD-L1 Tumor Proportion Score (TPS) ≥50%. In 2019, the FDA also approved pembrolizumab as the first-line treatment for advanced NSCLC patients with TPS ≥1%.However, previous studies showed concordance for TPC between lung biopsies and corresponding resected tumors was poor[1].Our aim is to explore the TPS association between CT/PET-CT guided percutaneous lung biopsies and corresponding resected tumors.

Methods: A total of 151 patients with operable NSCLC who has both whole surgical tissue sectionsand matched lung biopsies specimenwere enrolled. All tissue specimens were collected before any treatment. The PD-L1 antibody we used for PD-L1 expression detection was SP263 (Ventana, USA), which was the Blueprint PD-L1 IHC Assay Comparison Project recommended. The cut-off values of TPS were 1% and 50%. 80 patients underwent CT guided lung biopsies, while patients PET-CT guided lung biopsieswere 71.For PET-CT guided percutaneous biopsies, the area with ¹⁸F-FDG-avid focus was preferred.The concordance in surgery and biopsy for PD-L1 TPS using Cohen’s kappa coefficient.The PD-L1 expression status in tumor-infiltrating immune cells (IC) is evaluated by same procedure as additional exploration.

Results: 133 patients have surgical resected and matched tumor biopsy specimens. Most patients have lung adenocarcinoma (110/133), while patients with squamous cell carcinoma were 23. For acquired tumor specimens, the success rate of CT guided percutaneous biopsieswas 85% (68/80), and the PET-CT guided biopsies success rate was 91.5% (65/71).In all cases, PD-L1 expression was frequently uniform between surgical tissue and matched biopsy specimens (82.7%, 110/133) and κ value was equal to 0.72 (95% CI 0.61 -0.82, P<0.001). Regarding CT guided percutaneous biopsies, the concordance rate was 79.4% (54/68), and the κ value was 0.63 (95% CI 0.46 -0.79, P<0.001). PET-CT guided biopsies has higher concordance rate (87.7, 57/65) and κ value (0.80, 95% CI 0.66 -0.93, P<0.001). PD-L1 expression in IC was frequently discordant between surgical resected and matched biopsy specimens (κ value, in all cases, 0.33; CT guided percutaneous biopsies, 0.241; PET/CT guided percutaneous biopsies, 0.43, respectively). Conclusions:Our results indicate relatively strong association of the PD-L1 TPS between surgical resected and corresponding CT/PET-CT guided percutaneous biopsies tumors. Moreover, PET-CT guided percutaneous biopsies have higher biopsy success rate and concordance with surgical tissue sections compare with CT guided biopsies, that was consistent with the phenomenon that PD-L1 expression was correlated with FDG uptake in previous studies[2,3]. Although these results and the underline mechanism need to be further researched, they indicate that the daily routine evaluation of the PD-L1 expression in percutaneous biopsies (especially PET-CT guided biopsies) could be accurate in screening patients to anti-PD-1/PD-L1 therapy.