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Background <p>Epidermal growth factor receptor-mutated (<i>EGFR</i>-M+) non-small-cell lung cancer (NSCLC) represents a substantial proportion of lung cancer and remains associated with a considerable risk of postoperative recurrence despite advances in targeted therapies. The role of programmed death-ligand&#xa0;1 (PD-L1) expression in the perioperative treatment of <i>EGFR</i>-M+ NSCLC remains controversial. The gene mutation landscape of PD-L1 in <i>EGFR</i>-M+ NSCLC and its relationship with prognosis remain poorly understood.</p> Methods <p>We retrospectively included patients with <i>EGFR</i>-M+ NSCLC, including 43 patients with stage IB–IV disease who underwent immunotherapy combined with chemotherapy followed by surgery (NeoGroup) and 499 patients with stage IB–III disease undergoing surgery (AdjGroup). Disease-free survival, radiological response, pathological response, clinicopathological factors, and genomic characteristics were analyzed to evaluate their associations with PD-L1 tumor proportion score (TPS).</p> Results <p>The NeoGroup had objective response, pathological complete response, and major pathologic response rates of 44.2%, 18.6%, and 41.9%, respectively. A higher frequency of PD-L1 TPS ≥1% at baseline correlated with better radiological responses. Patients who had a major pathologic response also had a greater increase in PD-L1 TPS from baseline after therapy (<i>P</i> = 0.0195). In the AdjGroup (N = 499), PD-L1 TPS ≥50% independently predicted shorter disease-free survival. Patients with PD-L1 ≥1% more frequently harbored <i>TP53</i> co-mutations and had poorer survival in external cohorts.</p> Conclusion <p>PD-L1 plays a dual role in perioperative <i>EGFR</i>-M+ NSCLC, indicating higher recurrence risk after surgery while predicting improved response to immunochemotherapy. PD-L1 may serve as a biomarker to guide individualized perioperative treatment strategies in <i>EGFR</i>-M+ NSCLC. Prospective validation is still warranted.</p>

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The Role of PD-L1 in Treatment Decision-Making for Perioperative EGFR-Mutated Lung Cancer and its Genomic Analysis

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年5月27日

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  • Yi-Fan Qi,
  • Zhen-Bin Qiu,
  • Wei-Ye Huang,
  • Chao Zhang,
  • Rui Fu,
  • Guang-Ling Jie,
  • Xiong-Wen Yang,
  • Yi-Duo Lin,
  • Hong-Ji Li,
  • Qian Cui,
  • Jian Su,
  • Zhi Xie,
  • Ben-Yuan Jiang,
  • Xu-Chao Zhang,
  • Xue-Ning Yang,
  • Yi-Long Wu,
  • Wen-Zhao Zhong

摘要

Background

Epidermal growth factor receptor-mutated (EGFR-M+) non-small-cell lung cancer (NSCLC) represents a substantial proportion of lung cancer and remains associated with a considerable risk of postoperative recurrence despite advances in targeted therapies. The role of programmed death-ligand 1 (PD-L1) expression in the perioperative treatment of EGFR-M+ NSCLC remains controversial. The gene mutation landscape of PD-L1 in EGFR-M+ NSCLC and its relationship with prognosis remain poorly understood.

Methods

We retrospectively included patients with EGFR-M+ NSCLC, including 43 patients with stage IB–IV disease who underwent immunotherapy combined with chemotherapy followed by surgery (NeoGroup) and 499 patients with stage IB–III disease undergoing surgery (AdjGroup). Disease-free survival, radiological response, pathological response, clinicopathological factors, and genomic characteristics were analyzed to evaluate their associations with PD-L1 tumor proportion score (TPS).

Results

The NeoGroup had objective response, pathological complete response, and major pathologic response rates of 44.2%, 18.6%, and 41.9%, respectively. A higher frequency of PD-L1 TPS ≥1% at baseline correlated with better radiological responses. Patients who had a major pathologic response also had a greater increase in PD-L1 TPS from baseline after therapy (P = 0.0195). In the AdjGroup (N = 499), PD-L1 TPS ≥50% independently predicted shorter disease-free survival. Patients with PD-L1 ≥1% more frequently harbored TP53 co-mutations and had poorer survival in external cohorts.

Conclusion

PD-L1 plays a dual role in perioperative EGFR-M+ NSCLC, indicating higher recurrence risk after surgery while predicting improved response to immunochemotherapy. PD-L1 may serve as a biomarker to guide individualized perioperative treatment strategies in EGFR-M+ NSCLC. Prospective validation is still warranted.