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

Introduction

Lung cancer remains one of the leading causes of morbidity and mortality worldwide, with non-small cell lung cancer (NSCLC) accounting for approximately 85% of all cases (1). Notably, 30–40% of NSCLC cases are diagnosed at an advanced stage (III–IV). While surgery is the preferred treatment for resectable cases, fewer than 20% of patients are eligible for surgical intervention at diagnosis (2). Neoadjuvant therapy has proven effective in downstaging tumors, increasing surgical eligibility, and improving resection rates. These improvements help reduce the risk of recurrence and enhance prognosis (3-5).

Since the publication of the CheckMate-159 trial in 2018 (6), several studies—including NADIM-II (7), KEYNOTE-671 (8), AEGEAN (9), and Neotorch (10)—have demonstrated the safety and efficacy of immune checkpoint inhibitors in the neoadjuvant treatment of NSCLC from a significantly longer RFS and a higher percentage with pathological complete response (PCR) with chemotherapy than chemotherapy alone in patients with resectable NSCLC (even stage IIIA or IIIB). Ongoing research, such as the IMPOWER030 and RATIONALE-315 trials (11), continues to reinforce these findings, highlighting the potential of these therapies to improve postoperative survival outcomes.

The degree of pathological remission following neoadjuvant therapy is strongly correlated with prognosis and serves as a key marker of treatment efficacy in NSCLC patients. However, the optimal threshold for remission and its predictive value for long-term survival remain subjects of debate (12). Additionally, since pathological remission is determined postoperatively, there is limited research on preoperative indicators that could predict long-term survival and tumor recurrence in NSCLC. While most studies to date have focused on neoadjuvant chemotherapy, the differences in mechanisms, efficacy assessments, and prognostic implications between neoadjuvant immunotherapy and chemotherapy highlight the need for further investigation (13). Identifying factors influencing postoperative recurrence and predictors of long-term survival in NSCLC patients treated with neoadjuvant therapy remains a critical area for future research.

Previous articles reported that CEA and NLR can effectively predict the diagnosis and prognosis of lung cancer (14,15). However, there was few studies on the preoperative evaluation value of neoadjuvant therapy for NSCLC. With the process of preoperative neoadjuvant therapy, CEA and NLR indicators almost continue fluctuating, which may be worth researching.

This study aimed to retrospectively analyze real-world data to evaluate survival outcomes and prognostic factors in NSCLC patients who underwent surgery following neoadjuvant therapy. The objective was to provide insights into treatment efficacy, improve prognosis prediction, and refine management strategies for neoadjuvant therapy in NSCLC. We present this article in accordance with the STROBE reporting checklist (available at https://jtd.amegroups.com/article/view/10.21037/jtd-2024-1651/rc).

Methods

Subject of the study

Subject of the study (Figure 1)

Figure 1 Flowchart. ^†, include VATS/RVATS changed to open chest surgery. CT, computed tomography; GP, gemcitabine + platinum; I, immunotherapy (sintilimab or tislelizumab); MRI, magnetic resonance imaging; PP, pemetrexed + platinum; RVATS, robotic video-assisted thoracoscopic surgery; TP, paclitaxel + platinum; VATS, video-assisted thoracoscopic surgery.

This study retrospectively analyzed data from 150 NSCLC patients who underwent neoadjuvant therapy followed by video-assisted thoracoscopic surgery (VATS), open chest surgery, or conversion from thoracoscopic to open chest surgery at the Department of Thoracic Surgery, Fujian Medical University Union Hospital, between April 2019 and June 2023. Collected data included clinical information, computed tomography (CT) images obtained before neoadjuvant therapy (chemotherapy with or without immunotherapy) and surgery, details of neoadjuvant therapy, postoperative pathological diagnoses and remission status, and follow-up data after discharge.

Inclusion and exclusion criteria

Inclusion criteria: (I) patients who underwent neoadjuvant therapy before surgery; (II) resection of lung tumor lesions achieving R0 resection; (III) postoperative pathological confirmation of NSCLC.

Exclusion criteria: (I) insufficient clinical or imaging data; (II) cancer progression or distant metastasis before surgery; (III) history of prior lung tumor treatment; (IV) postoperative pathology indicative of non-NSCLC or recurrent NSCLC; (V) inability to achieve R0 resection or requiring palliative surgery; (VI) follow-up duration of less than one year or loss.

Neoadjuvant therapy

All patients underwent two to six cycles of neoadjuvant therapy before surgery. Routine evaluations—including blood tests, liver function tests, serum tumor markers, chest CT scans, and cranial magnetic resonance imaging (MRI)—were conducted prior to the initiation of neoadjuvant therapy and repeated after the second and fourth cycles of treatment.

Neoadjuvant chemotherapy regimens included: PP regimen: pemetrexed + platinum; TP regimen: paclitaxel + platinum; GP regimen: gemcitabine + platinum.

For immunotherapy, programmed cell death protein 1 (PD-1) inhibitors, including sintilimab and tislelizumab, were primarily administered in combination with chemotherapy. None of the patients received preoperative radiotherapy.

Criteria for evaluating neoadjuvant efficacy and grading postoperative pathological remission

The evaluation of neoadjuvant therapy efficacy was conducted according to the RECIST 1.1 criteria for solid tumors and the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) standards for grading adverse reactions.

• Complete response (CR): complete disappearance of all lesions and normalization of serum tumor markers.
• Partial response (PR): reduction of tumor lesion diameter by 30% or more compared to baseline.
• Stable disease (SD): reduction of tumor lesion diameter by less than 30% or an increase of no more than 20% compared to baseline.

Postoperative pathological remission was classified into the following grades based on the International Expert Consensus on Neoadjuvant Immunotherapy for NSCLC (16):

• Grade I: no or minimal tumor regression.
• Grade IIA: significant but incomplete tumor regression, with more than 10% viable tumor tissue.
• Grade IIB: less than 10% viable tumor tissue [classified as major pathological response (MPR)].
• Grade III: PCR.

In this study, Grades I and IIA were collectively referred to as non-objective response (non-OR). Clinical and pathological staging followed the American Joint Committee on Cancer 8th edition TNM staging system.

Clinical data

Clinical data included the following:

• Demographics: age at diagnosis, gender, smoking history.
• Tumor characteristics: PD-1 expression levels, pathological type, stage, and degree of tumor remission.
• Surgical details: surgical approach.
• Laboratory data: pre-neoadjuvant and pre-surgery body mass index (BMI), clinical TNM stage, carcinoembryonic antigen (CEA) levels, white blood cell (WBC) counts, neutrophil-to-lymphocyte ratio (NLR), etc.
• Imaging data: in this study, at least 2 radiologists with more than 5 years of experience in using chest CT imaging for diagnosis retrospectively reviewed the CT images and evaluated the tumor size, tumor location, size of mediastinal lymph nodes calcification, vacuole/cavity, pleural invasion. And they judged the reduction of lesion or lymph node volume based on a 10% reduction in length and diameter.

Surgical treatment

Following neoadjuvant therapy and a multidisciplinary consultation, patients underwent lobectomy. Surgical approaches included:

• VATS.
• Robotic video-assisted thoracoscopic surgery (RVATS).
• Conventional open chest lobectomy.
• Conversion to open chest lobectomy when necessary.

Routine clearance of mediastinal lymph nodes was performed, and all surgeries achieved negative margins (R0). No secondary surgeries were conducted for any enrolled cases.

Postoperative follow-up

Follow-up evaluations included pulmonary CT scans, abdominal ultrasounds, and cranial MRI scans every 3 months during the first postoperative year, followed by evaluations every 6–12 months thereafter. Annual follow-up was conducted either through outpatient visits or telephone calls.

In lost to follow up cases, a telephone interview was conducted to determine the late postoperative outcomes. If a patient’s death was confirmed via telephone but the exact date was unclear, the date of the last outpatient follow-up was recorded as the final follow-up date.

• Recurrence-free survival (RFS): time from surgery to recurrence or last follow-up.
• v Overall survival (OS): time from surgery to death from any cause or last follow-up.

Statistics

Survival curves were generated using the Kaplan-Meier method, with differences analyzed using the log-rank test. Correlations between clinical and pathological parameters and survival outcomes were assessed using univariate and multivariate Cox proportional hazards analyses.

• CEA cutoff values were set at 5.0 ng/mL (normal range).
• NLR cutoff values were set at the median (median: 5.04, range, 1.0–15.5).
• Variables with P<0.1 in the univariate analysis were included in the multivariate analysis.

Statistical analysis

• Continuous data following a normal distribution were expressed as mean ± standard deviation and analyzed using independent t-tests for comparisons between groups.
• Categorical data were expressed as percentages (%) and analyzed using the Chi-square (χ²) test or Fisher’s exact test.

All statistical analyses were conducted using SPSS software version 21 (IBM, Armonk, NY, USA), with statistical significance set at P<0.05.

Ethical statement

The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. The study was approved by the Fujian Medical University Union Hospital (No. 2024KY018). The requirement for signed informed consent was waived as the data retrospectively analyzed were anonymous and did not involve patient privacy.

Results

Clinical characteristics

In this study, data were collected from 150 NSCLC patients who underwent surgery after neoadjuvant therapy. Among these, 102 cases met the inclusion criteria for further analysis covering 96 males and 6 females; 75 cases of squamous cell carcinoma, 24 cases of adenocarcinoma, and 3 cases of other tumors; 88 cases received chemotherapy and immunotherapy, 14 cases received only chemotherapy; 68 cases underwent VATS and 34 cases underwent open chest surgery. The average CEA value of all was 8.51±21.63 ng/mL, and the average NLR value was 6.17±2.62. Clinical data prior to neoadjuvant therapy and postoperative pathological findings are summarized in Tables 1,2.

Follow-up results

A total of 18 patients died during the follow-up period, all due to tumor recurrence, which occurred in 29 patients overall. The 1- and 3-year OS rates were 93.14% (95/102) and 89.22% (91/102), respectively, while the RFS rates were 87.25% (89/102) at 1 year and 80.39% (82/102) at 3 years. The median follow-up duration was 24 months.

Analysis of postoperative prognostic factors in neoadjuvant patients

Univariate analysis was used to identify significant prognostic factors for RFS (P<0.1). The results indicated the following significant associations:

• Age [hazard ratio (HR) =2.001; 95% confidence interval (CI): 0.929–4.306; P=0.07].
• Smoking history (HR =2.214; 95% CI: 1.039–4.717; P=0.04).
• Pre-neoadjuvant CEA levels (HR =3.776; 95% CI: 1.782–7.999; P=0.001).
• Pre-neoadjuvant NLR (HR =3.188; 95% CI: 1.475–6.891; P=0.003).
• Post-neoadjuvant lymphadenectasis in the lung hilum and mediastinum (HR =0.468; 95% CI: 0.223–0.981; P=0.04).

Multivariate analysis confirmed that:

• Pre-neoadjuvant CEA levels (HR =12.190; 95% CI: 2.236–66.459; P=0.004).
• Pre-neoadjuvant NLR (HR =2.946; 95% CI: 1.325–6.552; P=0.008).

These remained independent prognostic factors for RFS (Table 3).

Similarly, univariate analysis identified the following as significant independent prognostic factors for OS (P<0.1):

• Pre-neoadjuvant CEA levels (HR =3.534; 95% CI: 1.369–9.121; P=0.009).
• Pre-neoadjuvant NLR (HR =3.599; 95% CI: 1.387–9.340; P=0.008).
• Pre-neoadjuvant clinical stage (HR =0.594; 95% CI: 0.368–0.960; P=0.03).

Multivariate analysis confirmed that:

• Pre-neoadjuvant CEA levels (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).

These remained independent predictors of OS (Table S1).

Analysis of postoperative prognostic factors in neoadjuvant patients

The 3-year RFS rate was 72.6% for patients with a pre-neoadjuvant CEA level <5.0 ng/mL (normal value), compared to 33.6% for those with CEA ≥5.0 ng/mL (P=0.001, Figure 2A). Similarly, the 3-year OS rate was 82.5% for patients with pre-neoadjuvant CEA <5.0 ng/mL, compared to 58.2% for those with CEA ≥5.0 ng/mL (P=0.009, Figure 2B).

Figure 2 Postoperative survival of NSCLC after neoadjuvant according to clinical prognostic factors. RFS (A) and OS (B) levels according to pre-neoadjuvant CEA index. RFS (C) and OS (D) levels according to NLR index before neoadjuvant. CEA, carcinoembryonic antigen; CI, confidence interval; HR, hazard ratio; NLR, neutrophil to lymphocyte ratio; NSCLC, non-small cell lung cancer; OS, overall survival; RFS, recurrence-free survival.

For patients with a pre-neoadjuvant NLR <5 (range, 1.0–15.5, median: 5.04), the 3-year RFS was 65.4%, whereas those with NLR ≥5 had a significantly lower RFS of 23.9% (P=0.003, Figure 2C). The corresponding 3-year OS rates were 81.8% for patients with pre-neoadjuvant NLR <5 and 40.8% for those with NLR ≥5 (P=0.008, Figure 2D).

The Kaplan-Meier survival curves showed a significant correlation between high pre-neoadjuvant CEA and NLR elevation with poor OS and RFS. For postoperative NSCLC patients with pre-neoadjuvant CEA ≥5.0 ng/mL or NLR ≥5, 3-year OS and RFS are lower, indicating that they need more aggressive clinical decision to prolong survival and prevent tumor recurrence.

Analysis of postoperative prognostic factors in neoadjuvant therapy patients

Tumor type groups

The patients were divided into two groups based on tumor type: 75 cases in the LUSC group and 27 cases in the non-LUSC group.

• LUSC group: both pre-neoadjuvant CEA (P=0.009) and NLR (P=0.002) were identified as significant independent prognostic factors for RFS in univariate and multivariate analyses. Additionally, smoking history (P=0.02) was found to be an independent predictor of RFS. For OS, only pre-neoadjuvant NLR (P=0.008) remained statistically significant (Table S2).
• Non-LUSC group: neither pre-neoadjuvant CEA nor NLR emerged as significant independent prognostic factors for RFS or OS in univariate analyses (P>0.05, Table S3).

Survival analysis in the LUSC group:

• Smoking status: the 3-year RFS was 67.8% for non-smokers and 27.1% for smokers (P=0.02, Figure 3A).
• CEA levels: patients with pre-neoadjuvant CEA <5.0 ng/mL had a 3-year RFS of 71.0%, compared to 30.3% for those with CEA ≥5.0 ng/mL (P=0.003, Figure 3B).
• NLR levels: the 3-year RFS was 67.4% for patients with pre-neoadjuvant NLR <5, compared to 30.0% for those with NLR ≥5 (P=0.004, Figure 3C).

Figure 3 RFS after NSCLC surgery after neoadjuvant according to different groups. LUSC group according to smoking history (A), LUSC group (B), PCR/MPR group (D) and LUSC + PCR/MPR group (F), according to CEA index before neoadjuvant. LUSC group (C), PCR/MPR group (E) and LUSC + PCR/MPR group (G) according to NLR level before neoadjuvant. CEA, carcinoembryonic antigen; CI, confidence interval; HR, hazard ratio; LUSC, lung squamous cell carcinoma; MPR, major pathological response; NLR, neutrophil to lymphocyte ratio; NSCLC, non-small cell lung cancer; PCR, pathological complete response; RFS, recurrence-free survival.

Tumor remission groups

Patients were also divided into two groups based on tumor remission status: the PCR/MPR group (59 cases) and the non-OR group (43 cases).

• PCR/MPR group: univariate and multivariate analyses identified pre-neoadjuvant CEA (P=0.006 and P=0.02) and NLR (P=0.01 and P=0.004) as significant independent prognostic factors for both RFS and OS (Table S4).
• Non-OR group: neither pre-neoadjuvant CEA nor NLR was found to be significant independent prognostic factors for RFS or OS (P>0.05). However, smoking history emerged as a significant independent predictor of both RFS (P=0.04) and OS (P=0.03) in univariate analysis (Table S5).

Survival analysis in the MPR group:

• CEA levels: patients with pre-neoadjuvant CEA <5.0 ng/mL had a 3-year RFS of 80.1%, compared to 39.2% for those with CEA ≥5.0 ng/mL (P=0.005, Figure 3D).
• NLR levels: the 3-year RFS was 72.8% for patients with pre-neoadjuvant NLR <5, compared to 34.3% for those with NLR ≥5 (P=0.01, Figure 3E).

Combined LUSC and PCR/MPR group analysis

In this study, 44 cases overlapped between the LUSC and PCR/MPR groups. Univariate and multivariate analyses revealed that pre-neoadjuvant CEA (P=0.002) and NLR (P=0.008) were statistically significant independent predictors of RFS (P<0.05, Table S6), demonstrating stronger predictive value compared to the other groups.

• CEA levels: patients with pre-neoadjuvant CEA <5.0 ng/mL had a 3-year RFS of 80.5%, compared to 25.9% for those with CEA ≥5.0 ng/mL (P=0.002, Figure 3F).
• NLR levels: the 3-year RFS was 72.1% for patients with pre-neoadjuvant NLR <5, compared to 36.4% for those with NLR ≥5 (P=0.008, Figure 3G).

Although pre loading with CEA <5.0 ng/mL and NLR <5 showed better 3-year RFS in both LUSC and PCR/MPR groups, the 3-year RFS in the PCR/MPR group was higher, reaching 80.1% and 72.8%, respectively. In addition, patients with overlapping LUSC and PCR/MPR groups had better 3-year RFS predictive value for CEA and NLR before neoadjuvant therapy (HR =7.51 and 5.627).

Differential expression of CEA in groups

Although pre-neoadjuvant CEA levels were identified as independent predictors of RFS and OS in the LUSC and PCR/MPR groups in this study (P<0.05), they showed no predictive value for the non-LUSC or non-OR groups (P>0.05). However, a statistically significant difference in pre-neoadjuvant CEA levels was observed between the LUSC and non-LUSC groups (P<0.05), with higher CEA expression noted in the non-LUSC group (Table 4).

Analysis of factors associated with postoperative tumor recurrence

In this study, 29 cases of postoperative tumor recurrence were identified, with a median recurrence time of 16 months. A comparison between patients with and without recurrence revealed several factors influencing the recurrence risk. Age ≥60 years, pre-neoadjuvant CEA levels ≥5 ng/mL, and pre-neoadjuvant NLR ≥5 were associated with a higher risk of recurrence. Conversely, PD-1 positivity before neoadjuvant therapy and mediastinal lymph node shrinkage after neoadjuvant therapy were linked to reduced recurrence rates (P<0.05, Figure 4, Table S7).

Figure 4 Factors associated with postoperative tumor recurrence. *, P<0.05; **, P<0.01; ***, P<0.001. C, chemotherapy; CEA, carcinoembryonic antigen before neoadjuvant; I, immunotherapy; LN, lymphadenectasis in hilum of lung and mediastinum after neoadjuvant; MPR, major pathological response; NLR, neutrophil to lymphocyte ratio before neoadjuvant; OR, objective response; PD-1, programmed cell death protein 1; PCR, pathological complete response; VATS, video-assisted thoracoscopic surgery.

Changes in pathological tumor remission and tumor size on CT images after neoadjuvant therapy and their impact on RFS and OS

According to Table 3, the degree of pathological tumor remission did not significantly predict RFS (P=0.29) or OS (P=0.54). Even when remission was categorized using thresholds of 30% and 50%, univariate analysis of RFS and OS remained statistically non-significant (P>0.05). Similarly, reductions in tumor diameter on CT images, whether by 25%, 50%, or 75%, did not show significance in predicting RFS and OS (P>0.05, Table S8). However, a correlation was found between a tumor diameter reduction of more than 50% and achieving PCR/MPR in the primary tumor, when the 50% tumor diameter reduction was used as the threshold (P=0.02, Table 5).

Discussion

Huai et al. reported survival analysis showed a significant correlation between high post-treatment NLR elevation with poor OS and RFS of NSCLC patients (17). However, there is few research on the predictive value of neoadjuvant biomarkers for postoperative survival. In recent years, only Provencio et al. have found that low pre-treatment levels of ctDNA significantly associated with improved RFS and OS in operable stage IIIA NSCLC (HR =0.20, 95% CI: 0.06 to 0.63; and HR =0.07, 95% CI: 0.01 to 0.39, respectively) (18).

CEA is a well-established tumor marker, primarily produced in the gastrointestinal tract, pancreas, and liver glycoproteins. It has long been used as a diagnostic and prognostic tool in colon cancer (19), but elevated levels are also seen in lung adenocarcinoma (20) and squamous cell lung carcinoma (21). The expression level of CEA in adults is associated with lung ectodermal tissue cancer and secreted in body fluids. It is an early detected embryonic cancer antigen marker. When tumors occur in the cavity organs, the release of glycoprotein components on the surface of cancer cell membranes can significantly promote a significant increase in CEA expression. Therefore, in NSCLC, CEA is used for diagnosis, treatment assessment, detecting recurrence, and evaluating prognosis. However, there is no consensus on its prognostic value in NSCLC (19), particularly in the context of neoadjuvant therapy. Our study found that elevated pre-neoadjuvant CEA levels were significant predictors of postoperative RFS and OS in NSCLC, especially in LUSC and those achieving PCR or MPR. However, CEA levels had no predictive value in the non-LUSC group (e.g., lung adenocarcinoma, lymphoepithelioma-like carcinoma) and in non-OR patients.

Neutrophils, have the ability to release a large amount of vascular endothelial growth factor (VEGF) and can also bind to VEGF, actively recruited to the tumor microenvironment, promote tumor cell proliferation, suppress T-lymphocyte activity, and enhance angiogenesis, invasion, and metastasis (22-24). In contrast, lymphocytes can promote the immune response of the human body and activate the immune function by inducing natural killer cells, macrophages, and other cells to directly kill or secrete a series of cytokines, limiting the growth and migration of tumors. Therefore, the decrease in lymphocytes indicates a decrease in the body’s resistance to tumors, creating conditions for the occurrence and development of tumors (25). The NLR serves as a marker of tumor-promoting inflammation versus antitumor immune response. Our findings support the use of NLR as a prognostic indicator for NSCLC patients undergoing neoadjuvant therapy and surgery. An NLR ≥5 was associated with poorer RFS and OS (P<0.05).

Previous studies suggest that LUSC responds better to neoadjuvant chemotherapy compared to LUAC (26-28), which aligns with our findings. In the LUSC + PCR/MPR group, we observed a higher risk of recurrence, with an HR of 5.627 (95% CI: 1.555–20.361) for RFS. These results emphasize the need for tailored postoperative strategies in LUSC patients, especially those achieving pathological remission after neoadjuvant therapy.

Tobacco use is strongly linked to LUSC, with more than 80% of LUSC patients being smokers (26). Tobacco contributes to LUSC initiation, progression, and metastasis, particularly after neoadjuvant therapy. Our study confirms that smoking is a significant predictor of reduced RFS in LUSC patients, highlighting the long-term detrimental impact of tobacco.

This study shows that advanced age (≥60 years) promotes tumor recurrence, consistent with previous findings linking older age to poorer prognosis in NSCLC (29). Elevated pre-neoadjuvant CEA and NLR levels are strongly associated with increased recurrence risk. PD-1 positivity, a protective factor, reduces recurrence risk, aligning with Forde et al.’s findings (30). Mediastinal lymph node shrinkage, indicative of treatment response, also plays a key role in preventing recurrence. Our study reinforces its value as a positive prognostic factor, consistent with the SAKK 16/00 study (31).

Pathological tumor remission and tumor volume reduction on CT images are valuable indicators of tumor regression post-neoadjuvant therapy. However, distinguishing between central tumors and atelectatic tissue can be challenging, particularly in cases involving trachea or bronchus invasion or lesions in the hilum (32). A tumor diameter reduction of over 50% on CT scans was significantly correlated with achieving PCR or MPR (P<0.05), while reductions of 25% or 75% did not show sufficient correlation. This suggests that a reduction of more than 50% is a useful indicator of pathological remission.

While the PCR/MPR group had better RFS and OS than the non-OR group, our analysis did not confirm PCR/MPR as a significant predictor of RFS or OS (P>0.05). Several limitations must be considered: the single-center, retrospective design with a small sample size may introduce selection bias, and the short median follow-up period of 24 months limits the long-term assessment. Additionally, some PD-1-positive patients (n=6) did not receive combination immunotherapy, possibly influencing outcomes. The lack of data on postoperative adjuvant therapies further limits the evaluation of their impact. Given these limitations, further validation of PD-1 positivity in predicting outcomes is needed. The cases in study mainly come from male populations in Asian cities, so the results may vary in other regions, rural areas, or female populations. Future research should incorporate larger sample sizes, longer follow-up periods, and multicenter collaborations to provide a clearer understanding of prognostic factors in NSCLC patients undergoing neoadjuvant therapy.

Based on the different levels of CEA and NLR before neoadjuvant therapy, the author suggests that clinical doctors adjust their clinical decisions in a timely manner. For patients with elevated levels, stricter surgical indications and procedure selection, more comprehensive mediastinal lymph node dissection, and more active postoperative adjuvant therapy should be emphasized, and LUSC patients should be encouraged to quit smoking.

Conclusions

This study shows that pre-neoadjuvant CEA and NLR levels are significant predictors of postoperative RFS and OS in NSCLC, especially in LUSC patients and those achieving PCR/MPR remission. Smoking history also plays a critical role in LUSC prognosis. A 50% reduction in tumor size on post-neoadjuvant CT scans strongly correlates with PCR/MPR remission. Key factors contributing to postoperative recurrence include age, CEA and NLR levels, PD-1 expression, and mediastinal lymph node shrinkage on CT images. These findings highlight the importance of incorporating these prognostic factors into clinical practice to improve patient outcomes. Certainly, due to the limitations of the single center, retrospective design, we look forward to more perspectives, multicenter trials to validate the findings and explore long-term outcomes.

Acknowledgments

None.

Footnote

Reporting Checklist: The authors have completed the STROBE reporting checklist. available at https://jtd.amegroups.com/article/view/10.21037/jtd-2024-1651/rc

Data Sharing Statement: Available at https://jtd.amegroups.com/article/view/10.21037/jtd-2024-1651/dss

Peer Review File: Available at https://jtd.amegroups.com/article/view/10.21037/jtd-2024-1651/prf

Funding: This work was supported by the National Natural Science Foundation of China (No. 82203307), the Fujian Provincial Health Technology Project (No. 2022GGA021), the Fujian Provincial Natural Science Foundation of China (No. 2022J01241), the Talent Fund Project of Fujian Medical University Union Hospital (No. 2021XH029), and the Scientific Research Fund of Fujian Medical University (No. 2021QH1027).

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-2024-1651/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. The study was approved by the Fujian Medical University Union Hospital (No. 2024KY018). The requirement for signed informed consent was waived as the data analyzed were anonymous and did not involve patient privacy.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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