Abstract
Background
Primary tumor surgical resection for stage IVA non-small cell lung cancer (NSCLC) patients remains controversial in the current era of molecular targeted agents (MTAs) and immune checkpoint inhibitors (ICIs). Clinical impact and perioperative safety of primary tumor resection for stage IVA NSCLC patients undergoing multimodal treatment were analyzed.
Methods
This was a retrospective review of stage IVA NSCLC patients (n=145) treated between 2011 and 2023 with (n=47) or without (n=98) primary tumor surgical resection. Propensity scores were estimated using clinical and demographic variables, with inverse probability of treatment weighting (IPTW) applied for adjusting treatment selection bias. Overall survival (OS) was analyzed using the Kaplan-Meier method and Cox proportional hazards model.
Results
Patients with missing data were excluded, and the results of 45 surgical and 73 non-surgical patients were included in the IPTW-adjusted analysis. Prior to the adjustment, the median OS in the surgical group was 47.2 months compared with 17.2 months in the non-surgical group [hazard ratio (HR): 0.38, 95% confidence interval (CI): 0.23–0.62; P<0.001], while those after IPTW adjustment were 36.5 and 21.1 months, respectively (HR: 0.44, 95% CI: 0.23–0.85; P=0.01). Subgroup analyses indicated significant benefits for age <75 years, Eastern Cooperative Oncology Group performance status 0, tumor size ≤5 cm, T1–2, and N0–2 disease, regardless of MTA or ICI use. Surgical resection was safely performed with low complication rates and no surgery-related mortality.
Conclusions
Primary tumor resection as part of multimodal treatment may be associated with improved survival in carefully selected stage IVA NSCLC patients.
Keywords: Non-small cell lung cancer (NSCLC); stage IV neoplasm; surgical procedures, operative; inverse probability weighting; multimodal therapy
Highlight box.
Key findings
• Primary tumor surgical resection may improve survival in selected patients with stage IVA non-small cell lung cancer (NSCLC) undergoing multimodal treatment.
What is known and what is new?
• Systemic therapy with targeted agents and immune checkpoint inhibitors is standard for stage IVA NSCLC, but surgery’s role is unclear.
• This single-institution retrospective study, applying inverse probability of treatment weighting, suggests that primary tumor resection may be associated with improved survival in carefully selected patients with low perioperative risk, supporting its potential role within multimodal treatment.
What is the implication, and what should change now?
• The findings indicate that surgical resection could be considered as a treatment option for select stage IVA NSCLC patients after careful multidisciplinary evaluation.
• Further multicenter prospective studies are needed to confirm the clinical utility and refine selection criteria for surgery in this population.
Introduction
Systemic therapy is standard for stage IVA non-small cell lung cancer (NSCLC), though advances in molecular targeted agents (MTAs), including tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs), have resulted in substantial survival improvement (1,2).
Due to its heterogeneity, stage IV NSCLC includes cases of oligometastasis, which is characterized by limited metastatic spreading and may potentially benefit from local consolidative therapy (LCT) (3). Thus, the TNM classification system (8th, 9th editions) notes stage IVA NSCLC as a distinct stage IV disease subcategory (4,5). Studies have shown that LCT improves clinical outcomes for patients with oligometastatic NSCLC, with radiotherapy the most frequently used modality (6,7). However, survival was shown to be superior in select stage IV NSCLC patients who underwent primary tumor surgical resection compared with radiotherapy (8), prompting subsequent investigations into such surgical resection (9-11).
Nevertheless, surgery as part of multimodal treatment for stage IVA NSCLC remains controversial, particularly with effective systemic therapies available. This retrospective study evaluated the clinical impact of primary tumor resection and perioperative safety in stage IVA NSCLC patients undergoing multimodal treatment including systemic therapy. We present this article in accordance with the STROBE reporting checklist (available at https://jtd.amegroups.com/article/view/10.21037/jtd-2025-1-2778/rc).
Methods
This retrospective study reviewed 145 patients with pathologically confirmed stage IVA NSCLC diagnosed at Yao Municipal Hospital between January 2011 and December 2023. The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. The study was approved by the Institutional Review Board of Yao Municipal Hospital (No. YMH020122-149) and individual consent for this retrospective analysis was waived. All patients had a confirmed diagnosis of NSCLC based on histological or cytological evaluation of the primary tumor or metastatic sites, or liquid biopsy when tissue sampling was not feasible. Patients were classified into the resected or non-resected group based solely on primary tumor resection status. Staging was performed according to the TNM classification, 9th edition. Baseline imaging primarily included computed tomography (CT) of the thorax and upper abdomen, 18F-fluorodeoxyglucose positron emission tomography-computed tomography (18F-FDG PET-CT), and magnetic resonance imaging (MRI) of the brain (12,13). Molecular profiling of tumor specimens from formalin-fixed paraffin-embedded (FFPE) or fresh frozen tissues was used to detect key oncogenic driver gene mutations and rearrangements, such as epidermal growth factor receptor (EGFR) mutations or anaplastic lymphoma kinase (ALK) rearrangements. Programmed death-ligand 1 (PD-L1) protein expression was assessed via immunohistochemistry.
Relevant clinicopathologic and perioperative data, including baseline characteristics, treatment details, and surgical variables, were retrospectively obtained from medical records. Treatment strategies, including the indication for surgical resection, were determined through multidisciplinary discussions involving thoracic surgeons, medical oncologists, and radiologists. Surgical resection of the primary tumor was considered on an individual basis after comprehensive evaluation of patient-related factors, disease extent, surgical risk, and the intended purpose of surgery. Patients in the resected group underwent various surgical procedures for primary tumor removal, including partial resection, segmentectomy, lobectomy, or bilobectomy; partial resection was defined as a planned excisional resection of the primary tumor and did not indicate intentional incomplete surgery.
Statistical analysis
Statistical analyses were performed with R, version 4.4.0 (The R Foundation for Statistical Computing, Vienna, Austria). Overall survival (OS) was defined as time from definitive diagnosis to death from any cause or final follow-up. Patients alive at their last follow-up or end of the study (December 2024) were censored. OS curves were estimated using the Kaplan-Meier method and survival disparity between groups with a log-rank test. Univariate Cox proportional hazards regression was used for OS predictor identification, with hazard ratio (HR) and 95% confidence interval (CI) values presented. For baseline characteristic differences between the surgical and non-surgical groups, inverse probability of treatment weighting (IPTW) using propensity scores, estimated via logistic regression incorporating relevant clinical covariates, was applied. Stabilized weights were used to minimize extreme value influence. To evaluate the propensity score model’s discriminatory ability, a receiver operating characteristic (ROC) curve was generated and area under the curve (AUC) was calculated. AUC values closer to 1.0 indicated a higher discriminative ability. OS curves were calculated using the IPTW-adjusted Kaplan-Meier method. IPTW-adjusted log-rank testing was used to compare survival curve differences.
Results
One hundred forty-five stage IVA NSCLC patients were included, with their clinical characteristics summarized in Table 1. Of these patients, 47 underwent surgical resection and 98 did not; 8 patients in the non-surgical group received local radiotherapy to the primary tumor. Local treatment for distant metastases was performed selectively for diagnostic or palliative purposes, with brain metastases generally considered for radiotherapy or surgery. The median follow-up time for the entire cohort was 13.1 months, calculated from initial diagnosis to death, last follow-up, or study cutoff. At the cutoff, 90 patients had died, 84 due to lung cancer. Survival outcomes for the entire cohort prior to IPTW were as follows. Median OS for the entire unadjusted cohort was 21.0 months, with 1-, 3-, and 5-year survival rates of 65.1%, 35.3%, and 20.2%, respectively. For the unweighted cohort, the median OS in the surgical group was 42.1 months compared with 15.7 months in the non-surgical group. The surgical resection group showed 1-, 3-, and 5-year survival rates of 84.7%, 54.5%, and 32.2%, respectively, and the non-surgical group 61.8%, 25.2%, and 12.9%, respectively (HR: 0.44; 95% CI: 0.28–0.71; P<0.001) (Figure S1).
Table 1. Clinical characteristics of patients with stage IVA NSCLC (n=145).
| Characteristics | Category | Resected (n=47) | Non-resected (n=98) | P value |
|---|---|---|---|---|
| Age at diagnosis, years | 71.0 (35.0–88.0) | 73.0 (44.0–93.0) | 0.04 | |
| Sex | Male | 35 (74.5) | 64 (65.3) | 0.34 |
| Female | 12 (25.5) | 34 (34.7) | ||
| ECOG PS | 0 | 34 (72.3) | 37 (37.8) | <0.001 |
| 1 | 6 (12.8) | 36 (36.7) | ||
| 2 | 7 (14.9) | 14 (14.3) | ||
| 3 | 0 (0.0) | 8 (8.2) | ||
| 4 | 0 (0.0) | 3 (3.1) | ||
| Smoker | Current | 21 (44.7) | 29 (29.6) | 0.11 |
| Former | 14 (29.8) | 40 (40.8) | ||
| Never | 12 (25.5) | 23 (23.5) | ||
| Unknown | 0 (0.0) | 6 (6.1) | ||
| BMI, kg/m2 | 22.0 (16.6–28.4) | 21.3 (14.2–35.6) | 0.37 | |
| Final histopathological diagnosis | Adenocarcinoma | 35 (74.5) | 67 (68.4) | 0.72 |
| Squamous cell carcinoma | 7 (14.9) | 21 (21.4) | ||
| Other | 5 (10.6) | 10 (10.2) | ||
| Tumor size, cm | 3.5 (1.3–9.0) | 4.5 (1.1–15.0) | 0.002 | |
| T stage | 1 | 4 (8.5) | 7 (7.1) | <0.001 |
| 2a | 18 (38.3) | 16 (16.3) | ||
| 2b | 8 (17.0) | 4 (4.1) | ||
| 3 | 7 (14.9) | 15 (15.3) | ||
| 4 | 10 (21.3) | 46 (46.9) | ||
| X | 0 (0.0) | 10 (10.2) | ||
| N stage | 0 | 17 (36.2) | 30 (30.6) | 0.01 |
| 1 | 6 (12.8) | 16 (16.3) | ||
| 2a | 12 (25.5) | 9 (9.2) | ||
| 2b | 7 (14.9) | 12 (12.2) | ||
| 3 | 5 (10.6) | 31 (31.6) | ||
| M stage | 1a | 28 (59.6) | 65 (66.3) | 0.46 |
| 1b | 19 (40.4) | 33 (33.7) | ||
| CEA, ng/mL | 8.4 (0.4–503.4) | 10.0 (0.9–1,674.0) | 0.16 | |
| CYFRA, ng/mL | 2.2 (0.6–16.3) | 4.2 (0.7–265.5) | <0.001 | |
| KL-6, U/mL | 317.9 (130.0–2,239.5) | 376.5 (135.0–11,862.7) | 0.11 | |
| Systemic anticancer therapy | Yes | 45 (95.7) | 68 (69.4) | <0.001 |
| No | 2 (4.3) | 30 (30.6) | ||
| MTA treatment | Yes | 14 (29.8) | 27 (27.6) | 0.85 |
| No | 33 (70.2) | 71 (72.4) | ||
| ICI treatment | Yes | 23 (48.9) | 30 (30.6) | 0.043 |
| No | 24 (51.1) | 68 (69.4) | ||
| Primary tumor irradiation | Yes | 0 (0.0) | 8 (8.2) | 0.054 |
| No | 47 (100.0) | 90 (91.8) | ||
| Local treatment of distant metastases | Yes | 12 (25.5) | 14 (14.3) | 0.11 |
| No | 35 (74.5) | 84 (85.7) | ||
| Diagnosis year | 2011–2016 | 14 (29.8) | 37 (37.8) | 0.46 |
| 2017–2023 | 33 (70.2) | 61 (62.2) |
Data are presented as median (range) or n (%). BMI, body mass index; CEA, carcinoembryonic antigen; CYFRA, cytokeratin 19 fragment; ECOG PS, Eastern Cooperative Oncology Group performance status; ICI, immune checkpoint inhibitor; KL-6, Krebs von den Lungen-6; MTA, molecular targeted agent; NSCLC, non-small cell lung cancer.
Surgical eligibility was determined through multidisciplinary discussion based on imaging findings and patient-related factors. Perioperative characteristics of the 47 patients who underwent primary tumor resection are summarized in Table S1. The purposes of primary tumor resection were broadly categorized as diagnostic (including molecular testing), palliative (such as infection or air-leak control), and consolidative as part of aggressive multimodal therapy. Partial resections (n=25) were mainly performed for diagnostic (n=24) or palliative purposes (n=1), without systematic lymph node dissection. Segmentectomy (n=3), lobectomy (n=18), and bilobectomy (n=1) were primarily performed for consolidative intent, except for three lobectomies done for palliation. Most of these cases underwent mediastinal lymph node dissection, with some cases limited to hilar dissection (1 in segmentectomy and 5 in lobectomy). Surgery was performed safely in all cases, with no reoperations or surgery-related mortality. Intraoperative complications occurred in two cases of diffuse bleeding requiring transfusion. Postoperative complications (8.5%) included prolonged air leak (Clavien-Dindo grade IIIa in 3, grade I in 1) and pneumonia (grade II in 1). The median interval from surgery to initiation or resumption of systemic therapy was 42 days.
Of 145 patients in the initial cohort, 47 underwent surgical resection and 98 did not. Propensity scores were estimated using clinical and demographic variables. The covariates incorporated into the propensity score model included, for example, age, sex, Eastern Cooperative Oncology Group performance status (ECOG PS), T, N, and M stage, and systemic anticancer therapy (all variables are shown in Table 2). After excluding patients with missing covariates, 45 surgical and 73 non-surgical cases comprised the unadjusted cohort prior to IPTW. The propensity score model showed good discrimination, with an AUC of 0.830 (95% CI: 0.753–0.906) (Figure S2). For potential treatment selection bias, IPTW based on estimated propensity scores was applied (Figure S3). Baseline characteristics before and after IPTW adjustment are summarized in Table 2. Prior to IPTW adjustment, the surgical group tended to have lower intrathoracic tumor burden, was more likely to receive systemic therapy, and demonstrated superior OS, with a median OS of 47.2 months (non-surgical group, 17.2 months). Surgical group 1-, 3-, and 5-year survival rates were 84.0%, 57.4%, and 34.0%, respectively, compared with 65.5%, 22.7%, and 8.4%, respectively, for the non-surgical group. Primary tumor surgical resection was significantly associated with improved survival (HR: 0.38; 95% CI: 0.23–0.62; P<0.001). Following IPTW adjustment, survival benefits associated with surgery remained. Median OS was 36.5 and 21.1 months in the surgical and non-surgical groups, respectively, with 1-, 3-, and 5-year survival rates of 75.9%, 52.1%, and 31.4% compared with 68.1%, 20.9%, and 9.2%, respectively. Again, surgical resection had a significant association with prolonged OS (HR: 0.44; 95% CI: 0.23–0.85; P=0.01) (Figure 1).
Table 2. Baseline characteristics before and after IPTW adjustment.
| Clinical factors | Pre-IPTW | With IPTW | |||||
|---|---|---|---|---|---|---|---|
| Resected (N=45) | Non-resected (N=73) | P value | Resected (N=137.2) | Non-resected (N=111.9) | P value | ||
| Age at diagnosis, years | 69.6 (9.9) | 72.6 (9.2) | 0.10 | 69.6 (8.5) | 72.3 (9.1) | 0.30 | |
| Sex, male | 33 (73.3) | 50 (68.5) | 0.73 | 108.0 (78.7) | 76.7 (68.5) | 0.34 | |
| ECOG PS, 2–4 | 5 (11.1) | 13 (17.8) | 0.47 | 11.2 (8.1) | 16.4 (14.7) | 0.32 | |
| Smoker | 0.52 | 0.67 | |||||
| Current | 19 (42.2) | 28 (38.4) | 72.3 (52.7) | 46.2 (41.3) | |||
| Former | 14 (31.1) | 30 (41.1) | 43.1 (31.4) | 42.6 (38.0) | |||
| Never/unknown | 12 (26.7) | 15 (20.5) | 21.8 (15.9) | 23.2 (20.7) | |||
| BMI, kg/m2 | 22.3 (2.8) | 22.1 (3.8) | 0.67 | 21.7 (2.7) | 22.1 (3.7) | 0.60 | |
| Final histopathological diagnosis | 0.41 | 0.95 | |||||
| Adenocarcinoma | 33 (73.3) | 47 (64.4) | 97.9 (71.4) | 77.8 (69.5) | |||
| Squamous cell carcinoma | 7 (15.6) | 19 (26.0) | 30.0 (21.9) | 24.7 (22.1) | |||
| Other | 5 (11.1) | 7 (9.6) | 9.3 (6.8) | 9.4 (8.4) | |||
| Tumor size, cm | 3.8 (1.9) | 4.8 (2.4) | 0.01 | 4.9 (2.3) | 4.5 (2.2) | 0.56 | |
| T stage | 0.009 | 0.78 | |||||
| 1a, 1b | 4 (8.9) | 5 (6.8) | 8.5 (6.2) | 10.8 (9.6) | |||
| 2a | 16 (35.6) | 15 (20.5) | 26.2 (19.1) | 26.0 (23.2) | |||
| 2b | 8 (17.8) | 3 (4.1) | 9.8 (7.1) | 7.8 (7.0) | |||
| 3 | 7 (15.6) | 14 (19.2) | 16.0 (11.6) | 19.5 (17.4) | |||
| 4 | 10 (22.2) | 36 (49.3) | 76.8 (56.0) | 47.9 (42.7) | |||
| N stage | 0.054 | 0.90 | |||||
| 0 | 16 (35.6) | 19 (26.0) | 33.2 (24.2) | 34.9 (31.2) | |||
| 1 | 6 (13.3) | 13 (17.8) | 26.1 (19.0) | 17.6 (15.7) | |||
| 2a | 11 (24.4) | 8 (11.0) | 19.5 (14.2) | 15.6 (13.9) | |||
| 2b | 7 (15.6) | 10 (13.7) | 13.8 (10.1) | 15.8 (14.1) | |||
| 3 | 5 (11.1) | 23 (31.5) | 44.5 (32.4) | 28.1 (25.1) | |||
| M stage, 1b | 18 (40.0) | 29 (39.7) | >0.99 | 79.1 (57.7) | 43.5 (38.9) | 0.20 | |
| CEA, ng/mL | 40.0 (102.3) | 84.3 (230.9) | 0.23 | 31.2 (88.9) | 67.0 (194.5) | 0.13 | |
| Systemic anticancer therapy | 43 (95.6) | 54 (74.0) | 0.006 | 99.3 (72.4) | 90.9 (81.2) | 0.61 | |
| MTA treatment | 14 (31.1) | 18 (24.7) | 0.58 | 28.1 (20.5) | 30.9 (27.6) | 0.48 | |
| ICI treatment | 22 (48.9) | 26 (35.6) | 0.22 | 59.3 (43.3) | 45.4 (40.6) | 0.86 | |
Continuous variables are presented as mean (standard deviation) and categorical variables are presented as n (%). BMI, body mass index; CEA, carcinoembryonic antigen; ECOG PS, Eastern Cooperative Oncology Group performance status; ICI, immune checkpoint inhibitor; IPTW, inverse probability of treatment weighting; MTA, molecular targeted agent.
Figure 1.
Kaplan-Meier overall survival curves comparing patients with (solid line) or without (dashed line) primary tumor resection, after excluding cases with missing covariates. (A) Unadjusted; (B) IPTW-adjusted. Shaded areas represent 95% confidence intervals. IPTW, inverse probability of treatment weighting.
Subgroup analyses conducted using IPTW-adjusted data identified patient subsets with greater surgical resection benefits (Figure 2). OS improvement was observed across the clinical subgroups, with statistically significant benefits. Representative examples include patients aged <75 years (HR: 0.26; 95% CI: 0.13–0.53; P<0.001) and with ECOG PS 0 (HR: 0.34; 95% CI: 0.14–0.81; P=0.02), primary tumor size ≤5 cm (HR: 0.40; 95% CI: 0.22–0.72; P=0.01), T1–2 disease (HR: 0.29; 95% CI: 0.14–0.58; P=0.001), and N0–2 disease (HR: 0.49; 95% CI: 0.25–0.98; P=0.043) (Figure S4). Similarly, survival benefit associated with resection was noted in patients without MTA (HR: 0.34; 95% CI: 0.14–0.81; P=0.02) or ICI (HR: 0.28; 95% CI: 0.13–0.64; P=0.002) administration. While that trend persisted in those who received MTAs (HR: 0.76; 95% CI: 0.33–1.76; P=0.52) or ICIs (HR: 0.63; 95% CI: 0.27–1.45; P=0.28), statistical significance was not reached.
Figure 2.
Forest plot showing summary of subgroup analysis results after IPTW adjustment. BMI, body mass index; CEA, carcinoembryonic antigen; CI, confidence interval; ECOG PS, Eastern Cooperative Oncology Group performance status; ICI, immune checkpoint inhibitor; IPTW, inverse probability of treatment weighting; MTA, molecular targeted agent.
Discussion
Primary tumor surgical resection was found to be associated with prolonged OS and acceptable perioperative risk in stage IVA NSCLC patients who received multimodal therapy, even after IPTW adjustment. The survival benefit was consistently observed across clinically relevant subgroups, supporting the role of surgery in appropriately selected patients.
Current guidelines do not clearly recommend primary tumor surgical resection in stage IV NSCLC cases, though the 2013 American College of Chest Physicians (ACCP) guidelines (Special Treatment Issues in Non-small Cell Lung Cancer) note potential benefits of LCT in patients with brain or adrenal metastases (14). Clinically, LCT is also performed for patients with extrathoracic metastases beyond these organs. Two recent phase 2 randomized controlled trials demonstrated LCT efficacy, primarily using radiotherapy, for oligometastatic NSCLC (6,7). Both found significant improvements, with median OS of 41.2 months and progression-free survival (PFS) of 14.2 months in the former, and PFS of 9.7 months in the latter, indicating clear benefits.
Surgical resection has also shown promise. Using data available in the Surveillance, Epidemiology, and End Results program, primary tumor surgical resection in selected stage IVA patients was found to result in survival benefit (15). In addition, several single-center retrospective studies have reported favorable outcomes of primary tumor surgical resection. Mitchell et al. compared LCT using radiotherapy (n=63) with that using surgery (n=55) for oligometastatic NSCLC patients, and noted a median OS of 55.2 months and 5-year OS of 48.0% in the surgical group, compared with 23.4 months and 24.2%, respectively, in the radiotherapy group (8). More recently, Antonoff et al. presented findings showing a median OS of 58.6 months in 30 patients who underwent surgery, with a 5-year survival rate of 60% (9). Similarly, Deboever et al. reported a median OS of 51.7 months and PFS of 9.4 months in a study of 52 patients (10). Furthermore, a recent two-institution retrospective study by Eisenberg et al., which included a relatively large cohort of 179 patients, reported a median OS of 77.9 months and a 5-year survival rate of 36.7% (11).
The present single-institution retrospective analysis focused on treatment-naïve NSCLC stage IVA patients (M1a, M1b) based on the current TNM classification. Following IPTW adjustment, the surgical group showed longer median OS compared with the non-surgical group (36.5 vs. 21.1 months; HR: 0.44). Subgroup analyses indicated longer survival in patients with younger age, good performance status, smaller tumor, and earlier T and N stages, and other favorable characteristics, highlighting the importance of careful patient selection. Notably, survival benefits were significant in those who did not receive MTAs or ICIs, suggesting a greater role for surgery in the absence of effective systemic agents. Regarding perioperative safety, surgical resection was associated with low morbidity, with no perioperative mortality noted. Most patients resumed systemic therapy postoperatively within a median of 42 days, with no substantial delays in subsequent treatment. These findings are consistent with earlier reports (8-11), while inclusion of a non-surgical comparison group adds context to the impact of surgical resection.
This study has some limitations. As a retrospective single-institution analysis, selection bias is possible. Some instances of metastasis were diagnosed clinically, which may have affected staging accuracy. Furthermore, surgery was possibly more likely to be performed in patients with favorable features and avoided in high-risk cases, further introducing bias. Although IPTW substantially improved baseline balance, residual confounding related to age and ECOG performance status may still have influenced the observed outcomes. Finally, the sample size, especially for the subgroups, limits generalizability and the robustness of prognostic analyses. This limitation also affected the handling of M1 subcategories in the IPTW analysis. Due to the limited cohort size, it was not feasible to adjust for each metastatic site individually. Including all detailed subcategories as separate covariates would have introduced a large number of additional variables, making stable estimation of the propensity scores impractical. Therefore, the M1 factor was adjusted using two broad categories (M1a and M1b). Notably, the distribution of specific metastatic sites was imbalanced between treatment groups in the raw dataset, and this imbalance persisted to some extent even after IPTW; although this was not a primary focus of the analysis, the detailed distributions are provided in Table S2 for the full raw dataset and in Table S3 for the cohort used for IPTW analysis to illustrate the underlying data composition. This information may also serve as a useful reference for understanding patient selection and interpreting outcomes in future studies. Residual imbalance in M1 subcategories may have influenced the observed outcomes, although the OS benefit associated with primary tumor resection remained apparent.
Conclusions
These findings suggest that primary tumor resection provides meaningful survival benefit for stage IVA NSCLC patients undergoing multimodal therapy. Surgical resection should be considered for appropriately selected cases. Accordingly, larger studies with more balanced propensity score matching and, ideally, prospective multicenter randomized controlled trials are warranted to validate these findings and further refine patient selection for surgical resection in stage IVA NSCLC.
Supplementary
The article’s supplementary files as
Acknowledgments
None.
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 Institutional Review Board of Yao Municipal Hospital (No. YMH020122-149) and individual consent for this retrospective analysis was waived.
Footnotes
Reporting Checklist: The authors have completed the STROBE reporting checklist. Available at https://jtd.amegroups.com/article/view/10.21037/jtd-2025-1-2778/rc
Funding: None.
Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-2025-1-2778/coif). The authors have no conflicts of interest to declare.
Data Sharing Statement
Available at https://jtd.amegroups.com/article/view/10.21037/jtd-2025-1-2778/dss
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