High PD-L1 expression as a negative prognostic factor in stage III but not in stage II gastric cancer.

BACKGROUND: The prognostic value of programmed death ligand-1 (PD-L1) expression in patients with gastric or gastroesophageal junction cancer (G/GEJC) at different stages remains unclear. We hypothesized that high PD-L1 expression is associated with poor survival in patients with pathological stage III (pIII) G/GEJC. AIM: To investigate the relation between PD-L1 expression and survival outcomes in patients with pathological stage II (pII)-pIII G/GEJC. METHODS: In this retrospective cohort study, we collected the clinicopathological data of 388 consecutive patients with pII/pIII G/GEJC who underwent gastrectomy without neoadjuvant therapy at Nanfang Hospital, Southern Medical University. Postoperative tissue samples were collected to evaluate PD-L1 expression. Combined positive score (CPS) ≥ 1 was defined as PD-L1-positive, and CPS ≥ 5 as high PD-L1 expression. Survival outcomes were analyzed using Kaplan-Meier and Cox proportional hazards models. RESULTS: In pII G/GEJC, no significant differences were found in 3-year disease-free survival (DFS; 88.5% vs 87.9%, P = 0.939) or 3-year overall survival (OS; 92.3% vs 89.9%, P = 0.621) between PD-L1-positive and PD-L1-negative groups or between high and low PD-L1 expression groups (3-year DFS: 91.8% vs 84.2%, P = 0.138; 3-year OS: 94.2% vs 88.4%, P = 0.233). In pIII G/GEJC, PD-L1-positive patients had poorer 3-year DFS (52.2% vs 67.8%, P = 0.030) and 3-year OS (65.1% vs 78.2%, P = 0.007) than PD-L1-negative patients. High PD-L1 expression was associated with significantly inferior 3-year DFS (50.2% vs 64.8%, P = 0.023) and 3-year OS (64.0% vs 75.1%, P = 0.036) compared to low PD-L1 expression. Multivariate analysis revealed that high PD-L1 expression was independently associated with shorter DFS (HR = 1.624, P = 0.027) and OS (HR = 1.653, P = 0.043) in patients with pIII G/GEJC. Sensitivity analyses confirmed the robustness of the OS findings. CONCLUSION: High PD-L1 expression serves as an independent adverse prognostic biomarker in stage III but not stage II G/GEJC. These findings indicate a stage-dependent prognostic value of PD-L1 expression in G/GEJC.