Programmed death-ligand 1 (PD-L1) guides immune checkpoint inhibitor use in non-small cell lung cancer (NSCLC), yet its variation by age and histology remains uncertain. We retrospectively evaluated 1,606 consecutive NSCLC cases (2017–2022) with PD-L1 immunohistochemistry (IHC) on formalin-fixed, paraffin- embedded samples. Patients were grouped by age (< 60, 60–79, ≥ 80 years) and tumor proportion score (TPS), categorized as < 1%, 1–49%, or ≥ 50%. Associations were tested using the ² test, and independent predictors were identified using multinomial logistic regression.

High PD-L1 expression (TPS ≥ 50%) occurred in 33.6% of patients, intermediate (1–49%) in 23.6%, and negative (< 1%) in 42.7%. Programmed death-ligand 1 expression ≥ 1% was most frequent in squamous cell carcinoma (63.0%), followed by adenocarcinoma (55.0%), and was least common in large cell carcinoma (36.0%; p = 0.002). Overall proportions of PD-L1 ≥ 1% did not differ significantly by age. However, patients aged ≥ 80 had nearly twice the likelihood of high expression compared to those < 60 (relative risk ratio, 1.92; 95% CI: 1.11–3.34; p = 0.02), independent of the histotype.

Programmed death-ligand 1 expression in NSCLC shows distinct histotype-related patterns and a modest, age-related trend toward higher values in the oldest group. These data support routine PD-L1 assessment and suggest that advanced age alone should not preclude consideration of immunotherapy. Findings may inform trial design and real-world treatment decision-making.