High PD-L1 expression correlates with lymph node metastasis in patients who have undergone radical surgery for primary pulmonary adenocarcinoma

Background: As the use of immune checkpoint inhibitors in postoperative adjuvant chemotherapy for patients with programmed death-ligand 1 (PD-L1)-expressing lung cancer has been increasing, it is important to accumulate knowledge on PD-L1. In this study, we retrospectively evaluated PD-L1 expression and the related background characteristics in patients who underwent radical surgery for primary pulmonary adenocarcinoma.

Methods: Of 673 non-small cell lung cancer (NSCLC) cases that underwent surgery at Iwate Medical University from January 2017 to December 2022, 453 cases were eligible for study participation. The cases were divided into three groups based on postoperative pathological diagnosis as PD-L1 tumor proportion score (TPS) of less than 1% (negative), 1–49% (low), and 50% or more (high), respectively.

Results: There were 263 patients in the negative group, 133 in the low group, and 57 in the high PD-L1 group. Comparative analysis between the high and low/negative groups revealed statistically significant differences in gender, Brinkman Index, carcinoembryonic antigen (CEA), maximum standard uptake value (SUV-max), visceral pleural invasion, venous invasion, EGFR gene mutation, and lymph node metastasis. Three-year relapse-free survival (RFS) rates among patients with pulmonary adenocarcinoma expressing higher levels of PD-L1 were significantly worse than those among patients expressing lower PD-L1 levels (P=0.006). In multivariate analysis, lymph node metastasis [odds ratio (OR): 2.14, 95% confidence interval (CI): 1.10–4.16, P=0.02] and SUV-max (OR: 6.08, 95% CI: 2.89–12.8, P<0.001) were independent factors related to high PD-L1 expression in patients who underwent radical surgery for primary pulmonary adenocarcinoma. Cox proportional hazards analysis revealed that both the presence of lymph node metastasis [hazard ratio (HR): 8.61, 95% CI: 2.48–29.86, P<0.001] and higher SUV-max (HR: 4.46, 95% CI: 1.33–14.93, P=0.01) were significantly associated with shorter RFS.

Conclusions: High PD-L1 expression correlates with lymph node metastasis and SUV-max in patients who underwent radical surgery for primary pulmonary adenocarcinoma. Lymph node metastasis and high SUV-max were identified as a potential independent risk factor for postoperative recurrence and might be a risk factor for recurrence in the postoperative period.

Keywords: Programmed death-ligand 1 (PD-L1); lung cancer; adenocarcinoma; lymph node metastasis; surgery

Submitted Jun 02, 2025. Accepted for publication Aug 15, 2025. Published online Oct 29, 2025.

doi: 10.21037/jtd-2025-1118

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Key findings

• This study demonstrated that 3-year recurrence-free survival (RFS) rates among patients with pulmonary adenocarcinoma expressing higher levels of programmed death-ligand 1 (PD-L1) were significantly worse than the corresponding rates among patients expressing lower PD-L1 levels. In multivariate analysis, lymph node metastasis and maximum standard uptake value (SUV-max) were independent factors related to high PD-L1 expression in the resected specimen obtained by radical surgery for primary pulmonary adenocarcinoma, and lymph node metastasis and high SUV-max were identified as a potential independent risk factor for postoperative recurrence.

What is known and what is new?

• While previous studies have often included mixed histological types or advanced-stage patients, this study specifically focuses on patients with primary pulmonary adenocarcinoma who underwent radical surgery, including early-stage cases. High PD-L1 expression in resected specimens may be associated with lymph node metastasis and high SUV-max. It might serve as a potential indicator of early postoperative recurrence.

What is the implication, and what should change now?

• In patients with high PD-L1 expression identified before surgery, clinicians should consider the possibility of lymph node metastasis when determining surgical strategy, including the extent of lymph node dissection. The relationship between high PD-L1 expression, lymph node metastasis, SUV-max and prognosis need to be carefully considered, although further case accumulation and accurate evaluation are needed to corroborate our findings.