Impact of imaging features on selecting limited lymph node resection for cT1N0M0 lung cancer

Introduction

The guidelines recommend systematic lymph node dissection (SND) for all resectable lung cancers to ensure complete resection and accurate staging, regardless of the tumor stage (1,2). However, extensive removal of lymph nodes (LNs) without metastasis not only fails to improve survival (3,4), but also increases the risk of damage to the mediastinal structure and the incidence of postoperative complications (5). Therefore, in clinical practice, many surgeons perform limited mediastinal lymphadenectomy (LML). However, LML may omit potential positive LNs (4), causing patients to miss the opportunity to receive adjuvant treatment and resulting in a poor prognosis (6).

The percentage of patients diagnosed with early-stage lung cancer has significantly increased in recent years. This necessitates a reconsideration of the LN evaluation strategy. To avoid unnecessary lymphadenectomy, it is crucial to improve the dependability and accuracy of preoperative prediction of N2 metastasis (7). Computed tomography (CT) and positron emission tomography/CT (PET/CT) has limitations in identifying N2 metastasis due to suboptimal sensitivity (8). Infiltrating mediastinal LN (mLN) staging significantly improves diagnostic accuracy, but it is disadvantageous due to increase cost and the risk of complications. The JCOG0201 trial found that the consolidation tumor ratio (CTR) is a superior predictor of pathological mLN status (9). A previous study suggested that tumor diameter of less than 1 cm is a predictor of negative nodal status (10). There is a lack of research that combines CTR and tumor size to analyze their relationship with N2 metastasis and surgical strategy.

The objective of this study was to evaluate the predictive value of combined CTR and tumor size for predicting N2 metastasis and procedure-specific outcome (SND vs. LML) in clinical T1N0M0 non-small cell lung cancer (NSCLC). We present this article in accordance with the STROBE reporting checklist (available at https://jtd.amegroups.com/article/view/10.21037/jtd-24-626/rc).

Methods

Patient selection

The study was conducted in accordance with the Declaration of Helsinki (as revised in 2013). The study was approved by the Ethics Committees of The First Hospital of Lanzhou University (No. LDYYLL2024-35), Henan Cancer Hospital (No. 2024-182-043), Affiliated Hospital of North Sichuan Medical College (No. 2024ER350-13), The First Affiliated Hospital of Chengdu Medical College (No. 2024CYFYIRB-SQ-15), and Henan Provincial People’s Hospital (No. 2024-23). Written informed consent for this retrospective analysis was waived. All participating hospitals were informed and agreed with the study. A total of 3,898 patients with clinically T1N0M0 lesions who underwent surgical resection and pathologically diagnosed with invasive NSCLC at the above five hospitals between 2016 and 2018 were reviewed. Exclusion criteria were as follows: (I) previous lung surgery history, preoperative adjuvant treatment or malignant history; (II) no chest CT scans within 1 month prior to surgery at the surgical facility; (III) multiple lung lesions; (IV) lesions located within two thirds of the lung on CT scans. Finally, a total of 2,126 patients with SND and 708 patients with LML for radiologically peripheral cT1N0 solitary nodule and pathologically invasive NSCLC were reviewed. All patients underwent video-assisted thoracoscopic surgery, which included lobectomy and sublobar resection (segmentectomy and wedge resection). The SND was defined as resection of at least three N1 stations and at least three N2 stations, including subcarinal LNs (11). LML was defined as dissection with an insufficient number of LN stations or omitting LN dissection.

Radiological and histological evaluation

The chest CT scans of all patients were reviewed by two researchers with lung window [width, 1,500 Hounsfield unit (HU); level, −400 HU] and mediastinal window (width, 400 HU; level, 40 HU). Tumor size was defined as the largest diameter in the axial plane. The CTR was calculated as the ratio of the maximum size of the solid component to the maximum tumor size on thin-section CT scan. For pure ground-glass opacity (GGO) nodules: CTR =0; for part-solid nodules: 0< CTR <1; and for pure-solid nodules: CTR =1. All lesions were classified into two groups: 0≤ CTR ≤0.5, 0.5< CTR ≤1. Subsolid nodules include pure GGO nodules and part-solid nodules. The detailed CT scanning parameters are shown in Appendix 1. The final pathologic diagnosis was made by pathologists based on the 2015 World Health Organization classification of lung cancers (12).

Patients follow-up

During the first 2 years, patients underwent follow-up every 3 months, which included abdominal ultrasonography or CT scans and chest CT scans. Subsequently, follow-up was conducted every 6 months for 3 to 5 years and then annually. Chest CTs, brain CT scans or magnetic resonance imaging were also performed. PET/CT scan or biopsy was recommended to confirm suspected recurrences. Recurrence-free survival (RFS) and overall survival (OS) were defined as the interval between the date of surgery and the first recurrence, death, or last follow-up.

Statistical analysis

The independent sample t-test and Pearson’s Chi-square test or Fisher’s exact test were used to compare continuous variables and categorical variables between groups respectively. Logistic regression analysis was conducted to identify the independent risk factors of N2 metastasis. The Kaplan-Meier method and log-rank test were used to estimate and compare RFS and OS among the groups. Finally, Cox proportional hazards regression was used to identify the independent prognostic factors for RFS and OS. The variables with a P value less than 0.10 in the univariate regression model were included in the multivariable regression model.

The statistical analysis was conducted using SPSS software (version 25.0, IBM) and R software (version 3.6.2, www.R-project.org). A significance level of two-sided P value less than 0.05 was used to determine statistical significance.

Results

Predictors of pathologic N2 metastasis

The analysis of predictors of N2 metastasis was conducted in 2,126 patients underwent SND, as SND is considered the gold standard for nodule staging. Table 1 presents the baseline characteristics of patients based on their pathological N2 status. Of the total patients, 8.5% (n=181) had N2 metastasis, out of which 5.4% (n=114) had both N1 and N2 metastasis and 3.1% (n=67) had only N2 metastasis. Patients with N2 positive had a higher number of N2 stations and LNs resected than those with N2 negative (both P<0.001). The median tumor size was 2.3 cm in the N2-positive group and 1.9 cm in the N2-negative group (P<0.001). The N2 positive group had a significantly higher proportion of patients with CTR >0.5 compared to the N2 negative group (98.9% vs. 54.2%, P<0.001).

The multivariate logistic analysis indicated that tumor size [odds ratio (OR) =2.05, 95% confidence interval (CI): 1.48–2.85, P<0.001], CTR (OR =43.64, 95% CI: 13.75–265.46, P<0.001), carcinoembryonic antigen (CEA: OR =2.26, 95% CI: 1.58–3.21, P<0.001), visceral pleural invasion (VPI) (OR =2.19, 95% CI: 1.36–3.44, P<0.001) were independent risk factors for N2 metastasis (Table 2). The N2 metastasis rate was significantly lower in GGO dominant tumors compared to solid dominant tumors (0.2% vs. 14.5%, P<0.001). In solid dominant tumors, the rate of N2 metastasis increased from 1.6% in tumors ≤1 cm to 19.3% in tumors between 2 and 3 cm (Figure 1). Therefore, we classified patients into two groups: group A included those with solid predominant tumors and diameter <1 cm, as well as those with GGO predominant tumors; group B included those with solid predominant tumors and diameter >1 cm. For the entire cohort, the positive rate of N2 in group A was close to 0, which was significantly lower than that in group B (0.2% vs. 14.2%, P<0.001). These finding suggest that patients in group A may be potential candidates for LML.

Figure 1 Prevalence of lymph node metastasis according to tumor density and tumor size. (A) Proportion of lymph node status stratified by tumor size in all patients; (B) proportion of lymph node status stratified by CTR and tumor size in all patients; (C) proportion of lymph node status stratified by tumor size in patients with subsolid nodules; (D) proportion of lymph node status stratified by tumor size in patients with pure-solid nodules. CTR, consolidation tumor ratio.

Prognostic analysis of patients based on the extent of lymph lode resection

The median follow-up period was 92.7 months. Table 3 shows the baseline characteristics of patients with SND and LML in group A and group B. In group A, there were significant differences in clinicopathological features between the SND and the LML with respect to the age, tumor size, tumor density, extent of surgery, Charlson Comorbidity Index (CCI), number of resected N2 stations and total LNs. There were no significant differences in sex, smoking history, CEA level, tumor location, histologic type, VPI, spread through air space (STAS) or adjuvant therapy between SND and LML in the two groups.

In the patients with group A, there was no significant difference in RFS (P=0.14) and OS (P=0.39) between the SND group and the LML group (Figure 2). However, in patients with group B, the SND group showed better RFS (P=0.03) and OS (P=0.02) than the LML group (Figure 2). Multivariate Cox regression analysis showed that SND was an independent predictor of favorable RFS [SND vs. LML: hazard ratio (HR) =0.71, 95% CI: 0.56–0.91, P=0.005] and OS (SND vs. LML: HR =0.66, 95% CI: 0.47–0.92, P=0.01) in group B. But univariate analysis in group A showed no significant difference in prognosis between SND and LML (RFS: SND vs. LML, HR =0.62, 95% CI: 0.28–1.37, P=0.24; OS: SND vs. LML, HR =0.51, 95% CI: 0.22–1.16, P=0.10) (Table 4). The survival results of subgroup analyses in group A defined by key clinical and demographic characteristics, including age, sex, smoking history, tumor size, CEA level, Eastern Cooperative Oncology Group (ECOG) performance status score, tumor location and histological type were consistent with the overall analysis in a post-hoc exploratory analysis (Figure 3).

Figure 2 Prognosis comparison according to extent of lymphadenectomy in group A and group B. (A) Recurrence-free survival according to extent of lymphadenectomy in group A and group B; (B) overall survival according to extent of lymphadenectomy in group A and group B. The survival was adjusted by age, sex, Charlson Comorbidity Index, smoking history, tumor size, tumor density, Eastern Cooperative Oncology Group performance status score, extent of surgery using multivariate Cox regression model. Group A: patients with CTR >0.5 and tumor size ≤1 cm or CTR ≤0.5; group B: patients with CTR >0.5 and tumor size >1 cm. LML, limited mediastinal lymphadenectomy; SND, system lymph node dissection; HR, hazard ratio; CI, confidence interval; CTR, consolidation tumor ratio.

Figure 3 Subgroup analysis of RFS and OS in patients with group A. Group A: patients with CTR >0.5 and tumor size ≤1 cm or CTR ≤0.5. CEA, carcinoembryonic antigen; ECOG, Eastern Cooperative Oncology Group; HR, hazard ratio; RFS, recurrence-free survival; CI, confidence interval; SND, system lymph node dissection; LML, limited mediastinal lymphadenectomy; OS, overall survival; CTR, consolidation tumor ratio.

In the entire cohort, the N2 detection rate of SND was significantly higher than that of LML (8.5% vs. 4.7%, P=0.001). We defined the N2 missed diagnosis rate of LML as the decrease in the N2 detection rate from LML to SND and the N2 missed diagnosis rate of LML was 3.8%. In patients with group B, the N2 detection rate of SND was still higher than that of LML (15.2% vs. 10.4%, P=0.04) and the N2 missed diagnosis rate of LML was 4.8%. However, in patients with group A, there was no significant difference in the N2 detection rate between SND and LML (0.3% vs. 0%, P=0.16) and the N2 missed diagnosis rate of LML was only 0.3%.

Prognostic analysis of patients based on the extent of surgery

The baseline characteristics of patients who underwent sublobar resection and lobectomy in the group A and group B are shown in Table S1. The clinicopathological characteristics were significantly different between sublobar resection and lobectomy in two groups with respect to age, tumor size, tumor density, location, ECOG performance status score and the number of resected N2 stations and LNs. In the patients with group A, there was no significant difference in RFS (P=0.56) and OS (P=0.44) between lobectomy and sublobar resection. In patients with group B, there was no significant difference in RFS (P=0.16) between lobectomy and sublobar resection. However, the lobectomy showed better OS (P=0.02) than sublobar resection (Figure S1). Multivariate Cox regression analysis showed that the extent of surgery was not an independent predictor of RFS but sublobar resection was an unfavorable predictor of OS (sublobar resection vs. lobectomy: HR =2.04, 95% CI: 1.26–3.31, P=0.004) in group B (Table 4). Extent of surgery was not an independent predictor of RFS or OS in group A (RFS: P=0.44; OS: P=0.20) (Table 4). The survival results of the subgroup analyses in group A were consistent with the overall analysis (Figure S2).

Discussion

In this study, we demonstrated the value of CTR combined with tumor size in predicting mLN metastasis. In patients with group A, LML showed a similar prognosis compared to SND and showed a low N2 missed diagnosis rate. Therefore, avoiding complete LN dissection under the guidance of CTR and tumor size may be a new strategy to reduce surgical trauma in early-stage lung cancer.

To minimize surgical damage to patients, it is important to preserve normal LNs and lung parenchyma (13). Maintaining a balance between accurate nodule staging and reducing damage to the mediastinal structure is a major challenge for surgeons. The key is to tailor a risk-based LN assessment strategy based on the biological characteristics of the tumor. However, achievement in minimizing damage from mLN dissection without compromising prognosis is still at an exploratory stage. Previous studies have suggested that patients with small tumor size (≤2 cm) may be the candidates for LML based on less LN metastasis (14-16), while others have suggested that the LN metastasis of small tumors should not be ignored (17,18). Tumors with GGO presence are less biologically aggressive than those with GGO absence (19-22). Previous studies have shown that the frequency of LN metastasis increases significantly with the increase of solid components in mixed ground-glass nodules (23,24). Therefore, we combined the tumor size and CTR to analyze the prevalence of N2 metastasis and found that the N2 metastasis rate of group A undergoing SND was significantly lower than that of group B undergoing SND (0.3% vs. 15.2%, P<0.001).

We further investigated the effect of N2 prediction by CTR combined with tumor size on procedure-specific outcomes (SND vs. LML; sublobar resection vs. lobectomy). Univariate Cox regression analysis showed that RFS and OS were similar in group A patients between SND and LML (RFS: P=0.24; OS: P=0.10). But multivariate Cox regression analysis in group B showed significant difference in prognosis between SND and LML (RFS: P=0.005; OS: P=0.01). In addition, the N2 missed diagnosis rate of LML increased from 0.3% in group A to 4.8% in group B. The worse prognosis of LML in patients with group B may be due to underestimation of nodal stage and missed appropriate adjuvant therapy. Therefore, the above results showed that: (I) LML may be a feasible strategy in patients with group A given its similar prognosis and staging accuracy to SND; (II) to ensure better prognosis and staging accuracy, SND remains the standard procedure for patients with group B. Similarly, the previous studies indicated that CTR ≤0.5 (25), tumor size less than 1 cm (26) are important predictors of negative nodal status in early-stage NSCLC. A recent prospective study suggested that patients with CTR ≤0.5 do not require mLN dissection in cT1N0 NSCLC (27). The LML in this study included but was not limited to omission of mLN dissection, so further studies are needed to verify this conclusion in terms of prognosis.

Significant progress has been made in preserving as much lung parenchyma as possible. The LCSG821 trial laid the foundation for lobectomy, which subsequently became the standard surgical procedure based on the fact that sublobar resection had a higher mortality and local recurrence rate than lobectomy for T1N0 lung cancer (28). Increased detection rates for early lung cancer have led to renewed interest in sublobar resection for early lung cancer. JCOG1211 is the first prospective study to demonstrate that segmentectomy should be considered as the standard of care for GGO-predominant clinical stage IA NSCLC (29). In this study, multivariate Cox regression analysis showed that sublobar resection achieved similar RFS (P=0.44) and OS (P=0.20) compared to lobectomy in group A. In JCOG0802/WJOG4607L, the tumor diameter was larger for solid or solid-predominant tumors. As a result, it was shown that lung parenchyma-preserving surgery had non-inferior survival compared with lobectomy (30). Therefore, sublobar resection may be a feasible strategy in patients with group A.

There were several limitations to this study. First, there may be potential differences in surgical management, such as differences in the extent of lung and mLN resection between different hospitals and surgeons. Although we were unable to assess the factors that influenced treatment decisions, we performed multivariate analyses to reduce selection bias as much as possible. Second, the assessment of CTR may be subjective, which may affect the promotion and use of this feature in clinical practice.

Conclusions

In conclusion, CTR combined with tumor size demonstrated predictive value for N2 status and procedure-specific outcome (SND vs. LML). It may assist surgeons in identifying appropriate candidates for LML using imaging information.

Acknowledgments

Funding: This work was supported by the Natural Science Foundation of Gansu Province (Nos. 21JR1RA092 and 21JR1RA118), the Natural Science Foundation of China (Nos. 82272943 and 82102126), and The First Hospital of Lanzhou University youth fund (No. ldyyyn2022-50).

Footnote

Reporting Checklist: The authors have completed the STROBE reporting checklist. Available at https://jtd.amegroups.com/article/view/10.21037/jtd-24-626/rc

Data Sharing Statement: Available at https://jtd.amegroups.com/article/view/10.21037/jtd-24-626/dss

Peer Review File: Available at https://jtd.amegroups.com/article/view/10.21037/jtd-24-626/prf

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-24-626/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 (as revised in 2013). The study was approved by the Ethics Committees of The First Hospital of Lanzhou University (No. LDYYLL2024-35), Henan Cancer Hospital (No. 2024-182-043), Affiliated Hospital of North Sichuan Medical College (No. 2024ER350-13), The First Affiliated Hospital of Chengdu Medical College (No. 2024CYFYIRB-SQ-15), and Henan Provincial People’s Hospital (No. 2024-23). Written informed consent for this retrospective analysis was waived. All participating hospitals were informed and agreed with the study.

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/.

References

1. Lardinois D, De Leyn P, Van Schil P, et al. ESTS guidelines for intraoperative lymph node staging in non-small cell lung cancer. Eur J Cardiothorac Surg 2006;30:787-92. [Crossref] [PubMed]
2. Howington JA, Blum MG, Chang AC, et al. Treatment of stage I and II non-small cell lung cancer: Diagnosis and management of lung cancer, 3rd ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest 2013;143:e278S-313S.
3. Watanabe S, Asamura H. Lymph node dissection for lung cancer: significance, strategy, and technique. J Thorac Oncol 2009;4:652-7. [Crossref] [PubMed]
4. Darling GE, Allen MS, Decker PA, et al. Randomized trial of mediastinal lymph node sampling versus complete lymphadenectomy during pulmonary resection in the patient with N0 or N1 (less than hilar) non-small cell carcinoma: results of the American College of Surgery Oncology Group Z0030 Trial. J Thorac Cardiovasc Surg 2011;141:662-70. [Crossref] [PubMed]
5. Cho HJ, Kim DK, Lee GD, et al. Chylothorax complicating pulmonary resection for lung cancer: effective management and pleurodesis. Ann Thorac Surg 2014;97:408-13. [Crossref] [PubMed]
6. Liang W, He J, Shen Y, et al. Impact of Examined Lymph Node Count on Precise Staging and Long-Term Survival of Resected Non-Small-Cell Lung Cancer: A Population Study of the US SEER Database and a Chinese Multi-Institutional Registry. J Clin Oncol 2017;35:1162-70. [Crossref] [PubMed]
7. De Leyn P, Dooms C, Kuzdzal J, et al. Revised ESTS guidelines for preoperative mediastinal lymph node staging for non-small-cell lung cancer. Eur J Cardiothorac Surg 2014;45:787-98. [Crossref] [PubMed]
8. Xia Y, Zhang B, Zhang H, et al. Evaluation of lymph node metastasis in lung cancer: who is the chief justice? J Thorac Dis 2015;7:S231-7. [PubMed]
9. Suzuki K, Koike T, Asakawa T, et al. A prospective radiological study of thin-section computed tomography to predict pathological noninvasiveness in peripheral clinical IA lung cancer (Japan Clinical Oncology Group 0201). J Thorac Oncol 2011;6:751-6. [Crossref] [PubMed]
10. Mokhles S, Macbeth F, Treasure T, et al. Systematic lymphadenectomy versus sampling of ipsilateral mediastinal lymph-nodes during lobectomy for non-small-cell lung cancer: a systematic review of randomized trials and a meta-analysis. Eur J Cardiothorac Surg 2017;51:1149-56. [Crossref] [PubMed]
11. Amin MB, Greene FL, Edge SB, et al. The Eighth Edition AJCC Cancer Staging Manual: Continuing to build a bridge from a population-based to a more "personalized" approach to cancer staging. CA Cancer J Clin 2017;67:93-9.
12. Travis WD, Brambilla E, Nicholson AG, et al. The 2015 World Health Organization Classification of Lung Tumors: Impact of Genetic, Clinical and Radiologic Advances Since the 2004 Classification. J Thorac Oncol 2015;10:1243-60. [Crossref] [PubMed]
13. Cheng X, Onaitis MW, D'amico TA, et al. Minimally Invasive Thoracic Surgery 3.0: Lessons Learned From the History of Lung Cancer Surgery. Ann Surg 2018;267:37-8. [Crossref] [PubMed]
14. Yu X, Li Y, Shi C, et al. Risk factors of lymph node metastasis in patients with non-small cell lung cancer ≤ 2 cm in size: A monocentric population-based analysis. Thorac Cancer 2018;9:3-9. [Crossref] [PubMed]
15. Veronesi G, Maisonneuve P, Pelosi G, et al. Screening-detected lung cancers: is systematic nodal dissection always essential? J Thorac Oncol 2011;6:525-30. [Crossref] [PubMed]
16. Watanabe S, Oda M, Go T, et al. Should mediastinal nodal dissection be routinely undertaken in patients with peripheral small-sized (2 cm or less) lung cancer? Retrospective analysis of 225 patients. Eur J Cardiothorac Surg 2001;20:1007-11. [Crossref] [PubMed]
17. Zhang Y, Sun Y, Shen L, et al. Predictive factors of lymph node status in small peripheral non-small cell lung cancers: tumor histology is more reliable. Ann Surg Oncol 2013;20:1949-54. [Crossref] [PubMed]
18. Pani E, Kennedy G, Zheng X, et al. Factors associated with nodal metastasis in 2-centimeter or less non-small cell lung cancer. J Thorac Cardiovasc Surg 2020;159:1088-1096.e1. [Crossref] [PubMed]
19. Tsutani Y, Miyata Y, Nakayama H, et al. Appropriate sublobar resection choice for ground glass opacity-dominant clinical stage IA lung adenocarcinoma: wedge resection or segmentectomy. Chest 2014;145:66-71. [Crossref] [PubMed]
20. Aokage K, Miyoshi T, Ishii G, et al. Influence of Ground Glass Opacity and the Corresponding Pathological Findings on Survival in Patients with Clinical Stage I Non-Small Cell Lung Cancer. J Thorac Oncol 2018;13:533-42. [Crossref] [PubMed]
21. Miyoshi T, Aokage K, Katsumata S, et al. Ground-Glass Opacity Is a Strong Prognosticator for Pathologic Stage IA Lung Adenocarcinoma. Ann Thorac Surg 2019;108:249-55. [Crossref] [PubMed]
22. Hattori A, Suzuki K, Takamochi K, et al. Prognostic impact of a ground-glass opacity component in clinical stage IA non-small cell lung cancer. J Thorac Cardiovasc Surg 2021;161:1469-80. [Crossref] [PubMed]
23. Murakawa T, Konoeda C, Ito T, et al. The ground glass opacity component can be eliminated from the T-factor assessment of lung adenocarcinoma. Eur J Cardiothorac Surg 2013;43:925-32. [Crossref] [PubMed]
24. Ding N, Mao Y, Gao S, et al. Predictors of lymph node metastasis and possible selective lymph node dissection in clinical stage IA non-small cell lung cancer. J Thorac Dis 2018;10:4061-8. [Crossref] [PubMed]
25. Zhang Y, Fu F, Wen Z, et al. Segment Location and Ground Glass Opacity Ratio Reliably Predict Node-Negative Status in Lung Cancer. Ann Thorac Surg 2020;109:1061-8. [Crossref] [PubMed]
26. Tsutani Y, Miyata Y, Nakayama H, et al. Prediction of pathologic node-negative clinical stage IA lung adenocarcinoma for optimal candidates undergoing sublobar resection. J Thorac Cardiovasc Surg 2012;144:1365-71. [Crossref] [PubMed]
27. Zhang Y, Deng C, Zheng Q, et al. Selective Mediastinal Lymph Node Dissection Strategy for Clinical T1N0 Invasive Lung Cancer: A Prospective, Multicenter, Clinical Trial. J Thorac Oncol 2023;18:931-9. [Crossref] [PubMed]
28. Ginsberg RJ, Rubinstein L. The comparison of limited resection to lobectomy for T1N0 non-small cell lung cancer. LCSG 821. Chest 1994;106:318S-9S. [Crossref] [PubMed]
29. Aokage K, Suzuki K, Saji H, et al. Segmentectomy for ground-glass-dominant lung cancer with a tumour diameter of 3 cm or less including ground-glass opacity (JCOG1211): a multicentre, single-arm, confirmatory, phase 3 trial. Lancet Respir Med 2023;11:540-9. [Crossref] [PubMed]
30. Saji H, Okada M, Tsuboi M, et al. Segmentectomy versus lobectomy in small-sized peripheral non-small-cell lung cancer (JCOG0802/WJOG4607L): a multicentre, open-label, phase 3, randomised, controlled, non-inferiority trial. Lancet 2022;399:1607-17. [Crossref] [PubMed]