Prognostic factors for non-small cell lung cancer after neoadjuvant therapy and surgery: a retrospective observational study

Background: Neoadjuvant therapy, given before surgery, improves surgical outcomes and survival in patients with non-small cell lung cancer (NSCLC). However, there is limited research on factors influencing postoperative survival and recurrence. This study aims to identify key prognostic factors following lung resection after neoadjuvant therapy.

Methods: We analyzed 102 NSCLC cases with preoperative neoadjuvant therapy, excluding 48 due to cancer progression, insufficient clinical data, loss to follow up, or follow-up duration of <1 year. The Kaplan-Meier and multivariable Cox regression model were used to assess prognostic factors for the time from surgery to recurrence or last follow-up [recurrence-free survival (RFS)] and the time from surgery to death from any cause or last follow-up [overall survival (OS)]. Statistical comparisons were performed using t-tests for continuous variables and Chi-square tests for categorical variables.

Results: Univariate and multivariate analyses identified pre-neoadjuvant carcinoembryonic antigen (CEA) and neutrophil-to-lymphocyte ratio (NLR) as significant predictors of both RFS [pre-neoadjuvant CEA: hazard ratio (HR) =12.190, 95% confidence interval (CI): 2.236–66.459, P=0.004; pre-neoadjuvant NLR: HR =2.946, 95% CI: 1.325–6.552, P=0.008] and OS (pre-neoadjuvant CEA: HR =3.545, 95% CI: 1.372–9.161, P=0.009; pre-neoadjuvant NLR: HR =3.783, 95% CI: 1.444–9.909, P=0.007) in NSCLC. And these factors were especially predictive in groups of lung squamous cell carcinoma (LUSC) and <10% residual tumor. CEA and NLR were stronger predictors of RFS than OS, with HRs of 7.751 and 5.627, respectively. Smoking was an independent predictor of RFS in LUSC patients (P<0.05). A >50% reduction in tumor size on post-neoadjuvant computed tomography (CT) correlated with minimal pathological response (P<0.05). Age, pre-neoadjuvant CEA, NLR, programmed cell death protein 1 (PD-1) levels, and changes in mediastinal lymph nodes on post-neoadjuvant CT were significantly associated with tumor recurrence (P<0.05).

Conclusions: Pre-neoadjuvant CEA and NLR are predictors of postoperative survival. Other factors, including tumor size reduction and PD-1 levels, should be considered in clinical decision-making.

Keywords: Neoadjuvant therapy; non-small cell lung cancer (NSCLC); carcinoembryonic antigen (CEA); neutrophil-to-lymphocyte ratio (NLR); survival

 

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Key findings

• Pre-neoadjuvant biomarkers: elevated carcinoembryonic antigen (CEA) (≥5.0 ng/mL) and neutrophil-to-lymphocyte ratio (NLR) (≥5) are significant predictors of postoperative recurrence-free survival (RFS) and overall survival (OS) in non-small cell lung cancer (NSCLC) patients. This is particularly notable among those with lung squamous cell carcinoma (LUSC) and patients achieving pathological complete response or major pathological response post-surgery.

• Smoking history: a significant predictor of RFS in LUSC patients.

• Factors influencing recurrence: key determinants include age, pre-neoadjuvant CEA and NLR levels, programmed cell death protein 1 (PD-1) expression, and mediastinal lymph node shrinkage observed on post-neoadjuvant computed tomography (CT) scans.

What is known and what is new?

• Prognostic assessment for NSCLC patients undergoing neoadjuvant therapy has historically been challenging, especially in predicting postoperative recurrence and long-term survival.

• Elevated pre-neoadjuvant CEA and NLR levels are now identified as significant markers for poorer RFS and OS, providing clearer prognostic insights for NSCLC patients.

What is the implication, and what should change now?

• These findings emphasize the need to integrate age, pre-neoadjuvant CEA and NLR levels, PD-1 expression, and CT-detected mediastinal lymph node changes into postoperative management strategies.

• Clinical practices should adapt to routinely evaluate these parameters to better stratify patients' risks and personalize postoperative care plans.

Cite this article as: Lin Y, Huang R, Liu Q, Yan X, Liao G, Pan M, Du J, Gong X, Qian J, Wu L, Zheng B, Chen C, Yang Z. Prognostic factors for non-small cell lung cancer after neoadjuvant therapy and surgery: a retrospective observational study. J Thorac Dis 2025;17(5):2841-2855. doi: 10.21037/jtd-2024-1651