Unveiling the heterogeneity: PD-L1 expression and metabolic activity in primary vs. metastatic NSCLC, a retrospective...

Programmed death-ligand 1 (PD-L1) expression was different in primary tumors (PT) and metastatic tumors (MT). Total-body positron-emission tomography/computed tomography (PET/CT) comprehensively visualizes primary lesions and metastases. We aimed to explore the heterogeneity of PD-L1 high expression and metabolic activity between primary and metastatic lesions in patients with non-small cell lung cancer (NSCLC).

Immunohistochemistry analysis (IHC) was conducted for PD-L1 expression on tumor cells (TC) and tumor-infiltrating immune cells (IC) with 22C3 antibody. PD-L1 positive scores on TC no less than 50% or IC no less than 10% was defined as high expression. Total 598 (456 adenocarcinoma (ADC) and 142 squamous cell lung carcinoma (SCC)) primary diagnosed NSCLC patients who underwent ¹⁸F-FDG-PET/CT imaging were collected retrospectively. The statistic methods included chi-square test, Mann Whitney test and multivariate regression.

598 patients included 441 with PD-L1 low expression and 157 high expression. In all subtypes and ADC, MT had higher PD-L1 high expression (P = 0.023 and P = 0.010, respectively). The maximum standard uptake value (SUVmax) of PD-L1 high expression was significantly higher than that of PD-L1 low expression, no matter in PT or MT (15.23 (8.85) vs 9.42 (8.34), P<0.001; 13.36 (5.55) vs 8.52 (6.93), P<0.001). The squamous-cell-carcinoma metastatic-lesion analyses were exploratory owing to the very small sample size and risk of type-II statistical error. Multivariate regression indicated that SUVmax was independently associated with PD-L1 high expression. In all metastatic sites, we compared the SUVmax of MT and paired PT and found SUVmax was higher in PT than MT in PD-L1 low expression subgroup (11.39 (8.12) vs 8.52 (6.93), P = 0.002). For lymph node metastases, SUVmax was significantly elevated in PT compared to MT in PD-L1 low expression (13.71 (7.95) vs 8.54 (7.30), P = 0.002), whereas no correlation was observed in PD-L1 high expression.

Both PD-L1 expression and metabolism exhibited heterogeneity between primary tumors and their metastases. Compared to the primary tumors, different types of metastatic tumors showed variations not only in PD-L1 expression but also in their metabolic parameter. Utilizing whole-body PET/CT imaging facilitates the selection of optimal biopsy sites by providing metabolic reference data pertinent to clinical practice.