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Comparing survival outcomes of localized tumor destruction, sublobar resection, and pulmonary lobectomy in stage IA non-small cell lung cancer: a study from the SEER database
European Journal of Medical Research volume 30, Article number: 76 (2025)
Abstract
Purpose
A large-scale comparative analysis was performed with the aim of comparing local tumor destruction (LTD), sublobar resection (SR), and pulmonary lobectomy (PL) for cancer-specific survival (CSS) and overall survival (OS) in stage IA non-small cell lung cancer (NSCLC).
Methods
In the Surveillance, Epidemiology, and End Results (SEER) database (2000–2021), we included patients with pathologically confirmed stage IA non-small cell lung cancer who were treated with LTD, SR, or PL. Comparison between groups was performed separately after 1:1 proportional propensity score matching (PSM) with a caliper value of 0.1. Kaplan–Meier analysis was performed to compare survival outcomes between groups.
Results
In the total cohort of 4437 LTD patients, 2425 SR patients, and 6386 PL patients, 84.18% of LTD-treated patients were older than 65 years, whereas 68.95% of SR-treated patients and 62.82% of PL-treated patients were older than 65 years. The CSS (HR = 0.756, 95% CI 0.398 ~ 1.436, P = 0.393) and OS (HR = 0.46, 95% CI 0.553 ~ 1.295, P = 0.442) of LTD were consistent with SR. Whereas LTD demonstrated lower CSS (HR = 0.603, 95% CI 0.378 ~ 0.940, P = 0.024) and OS (HR = 0.590, 95% CI 0.432 ~ 0.805, P < 0.001) than PL, but were consistent when the tumor size was ≤ 1 cm. The CSS (HR = 1.215, 95% CI 0.872 ~ 1.693, P = 0.249) of SR was consistent with PL, but OS (HR = 1.347, 95% CI 1.079 ~ 1.681, P = 0.008) was higher than PL, but were consistent when the tumor size was 1.1–3 cm.
Conclusions
In patients with stage IA non-small cell lung cancer, the CSS and OS of LTD were no worse than those of SR. Compared with PL, the CSS and OS of LTD were lower, but when the tumor size was ≤ 1 cm, the CSS and OS of LTD were no worse than those of PL.
Introduction
According to the American Cancer Society, lung cancer is the second most common cancer and the leading cause of cancer deaths worldwide [1, 2], and the 5-year relative survival rate for lung cancer is 22.9% [3], with non-small cell lung cancer (NSCLC) accounting for 85% of lung cancer-related diagnoses and deaths [4]. Surgery remains the first-line treatment for technically resectable clinical stage I non-small cell lung cancer (NSCLC) [5], including pulmonary lobectomy (PL), sublobar resection (SR) with/without lymph node dissection. Pulmonary lobectomy has been the standard treatment for stage I NSCLC, and the 5-year survival rate of lobectomy combined with mediastinal lymph node dissection is as high as 60% [6, 7]. However, removing too much healthy lung tissue may have a serious impact on patients’ quality of life. Therefore, in order to preserve the lung function of patients as much as possible, pulmonary sublobar resection including wedge resection, segmental resection and bronchial sleeve resection has received attention as a treatment modality for smaller lung tumors [8,9,10]. The advantage of pulmonary sublobar resection is that it not only preserves a larger lung reserve, but is also indicated for patients with poor baseline lung function or severe comorbidities. At the same time, the choice of surgery for smaller tumors is prone to controversy [11, 12].
Local tumor destruction (LTD), such as Laser ablation, cryosurgery, electrocautery and beam radiation, is another option for patients who cannot be treated surgically. Thermal ablation and stereotactic radiotherapy, among others, have been consistently recommended by the guidelines of international authorities such as the National Comprehensive Cancer Network (NCCN) and the Cardiovascular Interventional Society of Europe (CIRSE) as alternatives to surgery [13], especially for early-stage lung cancers with tumor sizes ≤ 3 cm, which may achieve the results of surgery [14, 15]. The principle of LTD is all about in situ inactivation of tumor cells for therapeutic purposes, thus achieving unprecedented local control in patients with inoperable early-stage NSCLC. With the detection of early-stage NSCLC increasing, the number of patients treated with local tumor destruction (LTD) is also increasing. This treatment modality is less invasive and maximizes preservation of lung function, but there are no large data research on survival outcomes in this population compared to surgery. Therefore, we relied on the SEER database (2000–2021) to include NSCLC patients in clinical stage IA to compare the efficacy of LTD vs PL vs SR.
Patients and methods
Data source and study population
This retrospective observational study obtained data on patients with stage IA NSCLC from SEER Research Data, 17 Registries, Nov 2023 Sub (2000–2021) [16] by using SEER*Stat software version 8.4.3. We developed inclusion exclusion criteria based on the study objectives. Inclusion criteria were as follows: (1) first diagnosis from 2000 to 2021; (2) ICD-O-3/WHO 2008 site code for Lung and Bronchus; (3) patients with only one primary tumor and size no more than 3 cm, identified as stage IA (American Joint Committee on Cancer 8th Edition); and (4) histologically confirmed NSCLC, according to ICD-O-3 Hist/behav histologic subtypes include adenocarcinoma (codes 8140, 8144, 8250, 8255, 8256, 8257, 8260, 8265, 8333, 8480, 8481, 8551), squamous cell carcinoma (codes 8070, 8071, 8072, 8083), neuroendocrine carcinoma (codes 8240, 8249, 8246, 8013), and other pathologic types; and (5) have a treatment regimen, have not received chemotherapy, and treatments include LTD (codes 00, 12, 13, 15, 19), SR (codes 20–25), or PL (codes 30, 33). Exclusion criteria were as follows: (1) unknown patient characteristics, unknown tumor size, and unknown treatment; (2) survival time of less than 1 month; and (3) incomplete follow-up information. Deaths were categorized as cancer-specific deaths (CSM, deaths attributed to lung cancer) or other causes of death (OCM, deaths attributed to any other cause) according to SEER mortality codes. Ultimately, based on these selection criteria, we have included a total of 13,248 assessable patients (Fig. 1).
Statistical analysis
We used 1:1 propensity score matching (PSM) with a caliper of 0.1 to reduce bias in some baseline information. We used logistic regression models to generate propensity scores and calculated the standardized mean difference (SMD) of baseline variables between the two groups of patients before and after matching, primarily for variables with an SMD > 0.1. Variables considered in the PSM analysis included sex, age, and race, tumor grade, pathology, and tumor size.
Categorical variables are expressed as frequencies and percentages and were compared by χ2-test or Fisher’s exact test. Continuous variables were expressed as mean ± SD and compared by independent samples Student’s t-test. Cox proportional risk model was used to assess the hazard ratio (HR) and 95% confidence interval (CI). The endpoints were overall survival (OS) and cancer-specific survival (CSS). Kaplan–Meier (K–M) analysis and log-rank test were used to compare the survival rates between LTD group and SR group, SR group and PL group, and LTD group and PL group in the matched population. To better compare LTD with the other two methods, we repeated the survival analyses in two different subgroups: (1) patients with tumor size ≤ 1 cm and (2) patients with tumor size 1.1–3 cm. Statistical analyses were performed using SPSS 26.0 (IBM Corp., USA), with statistically significant differences at P ≤ 0.05.
Results
Patient characteristics and survival outcomes of local tumor destruction group and sublobar resection group
4437 patients (64.66%) treated with LTD and 2425 patients (35.34%) treated with SR were included (Table 1). Before PSM, there were significant differences in sex, race, age, pathology grade, pathology, and tumor size between the LTD and SR groups (all P < 0.001). After PSM, the LTD group and the SR group were included in 475 patients and 475 patients, and the SMD values for most data in the PSM cohort were < 10%, which were all lower than before PSM. There were no differences in sex, race, age, pathology grade, pathology, and tumor size between the LTD and SR groups (all P > 0.1).
Before PSM, the Cox regression model showed that LTD was associated with lower rates of CSS and OS (HR = 0.252, 95% CI 0.197 ~ 0.323, P < 0.001; HR = 0.258, 95% CI 0.218 ~ 0.305, P < 0.001). After PSM, LTD was not associated with lower rates of CSS and OS (HR = 0.756, 95% CI 0.398 ~ 1.436, P = 0.393; HR = 0.46, 95% CI 0.553 ~ 1.295, P = 0.442). The K-M survival curves for CSS and OS are shown in Fig. 2. Among patients treated with LTD vs. SR, the CSS rates at 1-, 2-, and 3- years were 0.983 vs. 0.989, 0.973 vs. 0.975, and 0.945 vs. 0.973, respectively; the OS rates at 1-, 2-, and 3- years were 0.971 vs. 0.968, 0.947 vs. 0.945, and 0.888 vs. 0.935, respectively.
Survival outcomes of local tumor destruction group versus sublobar resection group after 1:1 propensity score matching in stage IA NSCLC. A Cancer-specific survival (CSS) of the overall cohort; B Overall survival (OS) of the overall cohort; C CSS of patients with tumor size ≤ 1 cm; D OS of patients with tumor size ≤ 1 cm; E CSS of patients with tumor size 1.1–3 cm; F OS of patients with tumor size 1.1–3 cm
To further clarify the survival differences between the two groups, we performed a subgroup analysis. In patients with tumor size ≤ 1 cm treated with LTD vs. SR, the 1-, 2- and 3-year CSS rates were 0.993 vs. 1, 0.993 vs. 1, 0.993 vs. 1, 0.993 vs. 1, respectively (P = 0.015); and the 1-, 2- and 3-year OS rates were 0.952 vs. 0.975, 0.952 vs. 0.966, and 0.894 vs. 0.950 (P = 0.262). In patients with tumor sizes of 1.1–3 cm treated with LTD vs. SR, the 1-, 2-, and 3-year CSS rates were 0.987 vs. 0.986, 0.973 vs. 0.966, and 0.949 vs. 0.963 (P = 0.785), respectively; and the 1-, 2-, and 3-year OS rates were 0.976 vs. 0.966, 0.946 vs 0.938, and 0.887 vs 0.930 (P = 0.872).
Patient characteristics and survival outcomes of local tumor destruction group and pulmonary lobectomy group
4437 patients (41.00%) treated with LTD and 6386 patients (59.00%) treated with PL were included (Table 2). Before PSM, the differences in sex, race, age, pathology grade, pathology, and tumor size were significant between the LTD and PL groups (all P < 0.001). After PSM, the LTD group and the PL group were included in 960 patients and 960 patients, with SMD values < 10% for most data in the PSM cohort. Differences in sex, age, pathology grade, pathology type, and tumor size were reduced in the LTD and PL groups, with no significant differences seen in race (P = 0.862).
Before PSM, the Cox regression model showed that LTD was associated with lower rates of CSS and OS (HR = 0.198, 95% CI 0.165 ~ 0.237, P < 0.001; HR = 0.204, 95% CI 0.180 ~ 0.231, P < 0.001). After PSM, LTD was still associated with lower rates of CSS and OS (HR = 0.603, 95% CI 0.378 ~ 0.940, P = 0.024; HR = 0.590, 95% CI 0.432 ~ 0.805, P < 0.001). The K-M survival curves for CSS and OS are shown in Fig. 3. Among patients treated with LTD vs. PL, the 1-, 2-, and 3-year CSS rates were 0.984 vs. 0.983, 0.961 vs. 0.978, and 0.940 vs. 0.971, respectively; and the 1-, 2-, and 3-year OS rates were 0.975 vs. 0.971, 0.932 vs. 0.958, and 0.877 vs. 0.945, respectively.
Survival outcomes of local tumor destruction group versus pulmonary lobectomy group after 1:1 propensity score matching in stage IA NSCLC. A Cancer-specific survival (CSS) of the overall cohort; B Overall survival (OS) of the overall cohort; C CSS of patients with tumor size ≤ 1 cm; D OS of patients with tumor size ≤ 1 cm; E CSS of patients with tumor size 1.1–3 cm; F OS of patients with tumor size 1.1–3 cm
We performed a subgroup analysis, and among patients treated with LTD vs. PL whose tumors were ≤ 1 cm in size, the 1-, 2-, and 3-year CSS rates were 0.990 vs. 0.992, 0.990 vs. 0.992, and 0.961 vs. 0.985 (P = 0.480), respectively; and the 1-, 2-, and 3-year OS rates were 0.981 vs. 0.977, 0.961 vs 0.969, and 0.893 vs 0.954 (P = 0.127). In patients with tumor sizes of 1.1–3 cm treated with LTD versus PL, the 1-, 2-, and 3-year CSS rates were 0.984 vs 0.982, 0.958 vs 0.976, and 0.937 vs 0.969, respectively (P = 0.041); and the 1-, 2-, and 3-year OS rates were 0.974 vs 0.970, 0.929 vs 0.957, and 0.875 vs 0.943 (P = 0.003).
Patient characteristics and survival outcomes of sublobar resection group and pulmonary lobectomy group
2425 patients (27.52%) treated with SR and 6386 patients (72.48%) treated with PL were included (Table 3). Before PSM, there were significant differences between the SR and PL groups in terms of race, age, pathology grade, pathology type, and tumor size (all P < 0.05) with the exception of sex. After PSM, the SR and PL groups included 2394 patients and 2394 patients, with SMD values < 10% for most data in the PSM cohort.
Before PSM, the Cox regression model showed that SR was not associated with a lower rate of CSS (HR = 0.783, 95% CI 0.597 ~ 1.033, P = 0.083), but was associated with a lower rate of OS (HR = 0.793, 95% CI 0.657 ~ 0.957, P = 0.015). After PSM, SR was associated with a higher rate of CSS (HR = 1.215, 95% CI 0.872 ~ 1.693, P = 0.249), but was associated with higher OS (HR = 1.347, 95% CI 1.079 ~ 1.681, P = 0.008). The K-M survival curves for CSS and OS are shown in Fig. 4. Among patients treated with SR versus PL, the 1-, 2-, and 3-year CSS rates were 0.992 vs. 0.984, 0.980 vs. 0.978, and 0.971 vs. 0.973, respectively; and the 1-, 2-, and 3-year OS rates were 0.976 vs. 0.963, 0.954 vs. 0.945, and 0.940 vs. 0.935, respectively.
Survival outcomes of sublobar resection group versus pulmonary lobectomy group after 1:1 propensity score matching in stage IA NSCLC. A Cancer-specific survival (CSS) of the overall cohort; B Overall survival (OS) of the overall cohort; C CSS of patients with tumor size ≤ 1 cm; D OS of patients with tumor size ≤ 1 cm; E CSS of patients with tumor size 1.1–3 cm; F OS of patients with tumor size 1.1–3 cm
We performed a subgroup analysis, and among patients with tumor size ≤ 1 cm treated with SR versus PL, the 1-, 2-, and 3-year CSS rates were 0.998 vs. 0.995, 0.995 vs. 0.985, and 0.991 vs. 0.980 (P = 0.133), respectively; and the 1-, 2-, and 3-year OS rates were 0.987 vs. 0.975, 0.980 vs 0.960, and 0.974 vs 0.946 (P = 0.020). In patients with tumor sizes of 1.1–3 cm treated with SR versus PL, the 1-, 2-, and 3-year CSS rates were 0.991 vs. 0.982, 0.975 vs. 0.976, and 0.965 vs. 0.971, respectively (P = 0.556); the 1-, 2-, and 3-year OS rates were 0.973 vs. 0.961, 0.946 vs. 0.942 and 0.930 vs 0.933, respectively (P = 0.074).
Discussion
Some studies have shown that the recurrence-free survival and overall survival of stage IA NSCLC treated with SR and PL are similar [8, 17, 18], but there is a lack of large-scale studies to demonstrate this. In recent years, with the emergence of local therapy for tumors, it provides a new treatment modality for many patients who do not want to undergo surgery or cannot tolerate surgery, especially elderly patients. Local tumors treatments such as thermal ablation and radiotherapy are considered to be alternative treatments to surgery, especially for early stage lung cancers [14], but the actual efficacy is controversial. In our study, we enrolled stage IA NSCLC patients treated with LTD, SR and PL based on the SEER database, and compared the CSS and OS of these groups after PSM, and we also performed subgroup analysis.
In the total cohort of 4437 LTD patients, 2425 SR patients and 6386 PL patients, 84.18% of LTD-treated patients were older than 65 years, while 68.95% of SR-treated patients and 62.82% of PL-treated patients were older than 65 years. Age is usually associated with mortality, and whether there is a survival benefit is subject to uncertainty. The principle of LTD is in situ tumor inactivation, which does not involve lymph node clearance and in principle has a higher likelihood of recurrence. In our study, the CSS and OS of LTD were noninferior to SR, but CSS of LTD was lower than that of SR when tumor size ≤ 1 cm; the CSS and OS of LTD were significantly lower than that of PL, but CSS and OS of LTD were noninferior to that of PL when tumor size ≤ 1 cm. If LTD may represent a therapeutic option, it should be taken into account when making clinical decisions and obtaining informed consent. In particular, when tumor size ≤ 1 cm, LTD demonstrated efficacy consistent with surgery. LTD may be a valid option for individuals for whom contraindications to surgery or considerations of preserving lung function outweigh the disadvantages of cancer control. If the treatment option of LTD is chosen, patients must be carefully informed of the general uncertainty associated with LTD at least until more reliable evidence becomes available. However, in elderly, comorbid, and surgery-intolerant patients, LTD demonstrated control rates consistent with SR, and in particular, showed control rates consistent with PL for tumor size ≤ 1 cm. Therefore, a high-quality prospective study of LTD in NSCLC using appropriate controls and adequate follow-up would provide more adequate evidence and elevate the status of the LTD technique in NCCN guidelines.
Furthermore, with advances in surgical techniques, it is becoming more common to preserve lung function as much as possible during the procedure, especially in older patients or those with comorbid chronic lung disease. The benefit of sublobar resection is the preservation of lung function as measured by expiratory flow rate [19, 20]. In a study comparing SR with PL [8], it was observed that the reduction in expiratory flow on exertion was lower after sublobar resection than after lobectomy. Although this difference is arguably not clinically significant for patients with normal lung function at baseline, it may be more clinically significant in patients with impaired lung function or in patients with lung disease, as lobectomy leads to greater impairment of lung function. The study also noted that the rate of locoregional recurrence was slightly higher after sublobar resection than after lobectomy, but the difference was not clinically significant. Another study [17, 21] confirmed that segmental resection was not inferior to lobectomy in patients with small-sized peripheral NSCLC, but the local recurrence rate was significantly higher after sublobar resection than after lobectomy. A previous meta-analysis [22] comparing SR and PL for the treatment of stage IA NSCLC showed that patients receiving SR had shorter postoperative hospitalization, but the two treatments demonstrated comparable short- and long-term outcomes. In our study, there was no difference in CSS of SR compared to PL, but OS of SR was significantly higher than PL, and the same finding was observed in tumor size ≤ 1 cm. This may be due to the fact that for smaller tumors, SR preserve more lung function. However, there was no statistically significant difference in CSS and OS of SR compared to PL in tumor size of 1.1–3 cm.
Age, comorbidities, tumor characteristics and quality of life may influence clinical decision-making in patients with stage IA NSCLC [23, 24]. In our opinion, LTD may be an alternative therapeutic strategy for the elderly and those with health risks, especially for small-sized tumors.
However, this study has some limitations. First, the nature of retrospective studies and the strict screening criteria in this study inevitably led to selection bias. Considering the shortcomings of retrospective analysis, further prospective analysis is recommended to confirm our study. Second, the data from the SEER database lacked some detailed baseline information (imaging findings, lung function indices, and comorbidities), which may influence clinical decision making and the accuracy of the results. Third, we included laser ablation and electrocautery, which achieve local tumor destruction, in the LTD group, but the number was small, and most of patients treated with beam radiation. Whether the difference in treatment modalities may lead to biased results requires further study. Fourth, the only available information in the SEER database was about the initial treatment, and the follow-up treatment of the patients was not clear, which may also affect the survival outcome.
Conclusions
In patients with stage IA NSCLC, LTD demonstrated consistent CSS and OS compared with SR; LTD demonstrated inferior CSS and OS compared with PL, while there was no difference in outcomes when tumor size was ≤ 1 cm. SR had non-inferior CSS and superior OS compared to PL, while there was no difference in outcomes when tumor size was 1.1–3 cm. Future large-scale and cross-regional randomized clinical trials are needed to validate these findings and explore the impact of treatment on long-term lung function.
Availability of data and materials
All data generated for this analysis were from the SEER database. The code for the analyses will be made available upon request.
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Funding
This study has received funding by Chinese Academy of Medical Sciences Clinical and Translational Medicine Research Special. NO.2023-I2M-C&T-A-013.
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Dr. Lin Cheng: Data curation; Formal analysis; Methodology; Software; The first author/Writing—original draft. Sheng-Wei Li: Data curation. Xiao-Guang Li: Funding acquisition; Project administration; Supervision; review & editing; corresponding author. Its publication is approved by all authors. All authors are in agreement with the content of the manuscript.
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Cheng, L., Li, SW. & Li, XG. Comparing survival outcomes of localized tumor destruction, sublobar resection, and pulmonary lobectomy in stage IA non-small cell lung cancer: a study from the SEER database. Eur J Med Res 30, 76 (2025). https://doi.org/10.1186/s40001-025-02325-9
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DOI: https://doi.org/10.1186/s40001-025-02325-9