Intentional sublobar resection versus lobectomy for non-small cell lung cancer ≤3 cm, including solid ground-glass nodules: a real-world study

Introduction

Non-small cell lung cancer (NSCLC) accounts for approximately 85% of all newly diagnosed lung cancer cases and is still the leading cause of cancer-related death worldwide (1). Surgical resection remains the cornerstone of treatment for early-stage NSCLC, as it enables complete tumor resection while preserving lung function (2). In 2011, the National Lung Screening Trial reported that low-dose computed tomography (CT) screening was associated with a decreased risk of lung cancer-related mortality (3,4). Low-dose CT has subsequently been widely adopted in clinical practice, leading to the increased detection of small lung tumors, especially non-solid lesions presenting as ground-glass opacities (GGOs) (5,6).

Lobectomy has served as the “gold-standard” therapeutic approach for early-stage lung cancer since 1995 (7,8). However, growing evidence suggests that sublobar resection can provide comparable long-term prognostic results and preserve lung function in appropriately selected patients (9-11). In recent years, sublobar resection has been widely applied. Sublobar resection includes segmentectomy and wedge resection, both of which differ significantly from traditional lobectomy. Notably, sublobar resection better preserves lung function, and lung wedge resection in particular is associated with reduced surgical complexity, a shorter operative time, and fewer perioperative complications (12,13).

Results from the JCOG0802/WJOG4607L trial showed that in patients with peripheral adenocarcinomas measuring ≤2 cm in size and a consolidation-to-tumor ratio (CTR) between 0.5 and 1 (excluding 0.5), segmentectomy resulted in better overall survival (OS) compared with lobectomy, but no significant difference in RFS was observed between segmentectomy and lobectomy (14,15). However, subsequent 10-year follow-up results from the JCOG0802 trial demonstrated that segmentectomy was associated with a higher RFS than lobectomy, with no significant difference in OS between the two surgical approaches (16).

Results from the JCOG1211 clinical investigation further indicated that segmentectomy achieved favorable survival outcomes in patients with NSCLC ≤3 cm and a GGOdominant pattern (CTR ≤0.5), including those with GGO lesions >2 cm (17,18). Although numerous studies have reported comparable survival outcomes between sublobar resection and lobectomy in patients with GGO-predominant NSCLC (19-21), controversy continues regarding both the short-term and 10-year long-term outcomes of lobectomy compared with sublobar resection in GGO-dominant NSCLC with a tumor size ≤3 cm and a CTR ≤1. Thus, the present study aimed to evaluate these two surgical approaches. We present this article in accordance with the STROBE reporting checklist (available at https://jtd.amegroups.com/article/view/10.21037/jtd-2026-1486/rc).

Methods

This retrospective study consecutively enrolled patients with GGO NSCLC (tumor size ≤3 cm and CTR ≤1) who underwent intentional video-assisted thoracoscopic surgery (VATS) lobectomy or sublobar resection at Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, between January 2014 and December 2015. The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. The study was approved by the ethics board of Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University (No. 2026225701) and individual consent for this retrospective analysis was waived.

The CT images were independently reviewed by three surgeons, and the CTR was calculated according to the established Fleischner Society criteria. The inclusion criteria were as follows: (I) tumor size ≤3 cm; (II) a pathologically confirmed diagnosis of a malignant lung tumor; (III) availability of complete imaging examinations; (IV) American Society of Anesthesiologists (ASA) grade I–II; (V) organ function and adequate cardiopulmonary function; and (VI) age between 18 and 85 years. The exclusion criteria were as follows: (I) distant metastases; (II) absence of pretreatment imaging examinations; (III) a clinically significant concurrent malignant tumor; and/or (IV) incomplete data or loss to follow-up (Figure 1).

Figure 1 Study flowchart. ASA, American Society of Anesthesiologists; VATS, video-assisted thoracoscopic surgery.

The choice of surgical procedure (sublobar resection or lobectomy) was determined by surgeons after thorough discussion. Systematic or selective lymph node dissection was routinely performed. The chest tube was removed when the chest radiograph showed good lung expansion, the 24-hour pleural drainage volume was ≤300 mL, and no air leakage was observed.

Patients were evaluated at the outpatient clinic 2 weeks after surgery. Subsequently, patient follow-up assessments were conducted every 4–6 months for the first 2 years, every 6 months for the next 3 years, and annually thereafter, including chest CT, B-ultrasound, and blood tests. Brain magnetic resonance imaging and bone scans were performed every 2 years to detect local recurrence or metastasis. Patients who could not attend follow-up visits at the hospital were contacted by telephone every 6 months. The last follow-up was conducted in December 2025.

The primary endpoints were OS and recurrence-free survival (RFS). The secondary endpoints included postoperative perioperative outcomes and postoperative complications.

Statistical analysis

Categorical variables were presented as frequencies and percentages, with between-group comparisons performed using Pearson’s Chi-squared test or Fisher’s exact test, as appropriate. Continuous variables were summarized as mean and standard deviation, and intergroup differences were analyzed by one-way analysis of variance or the Kruskal-Wallis test, Mann-Whitney U test or independent two-sample t-tests as appropriate. Statistical analyses were conducted using SPSS (version 27.0, IBM, Armonk, NY, USA). A two-sided P value <0.05 was considered statistically significant. Baseline characteristics, perioperative indicators, and postoperative complications were matched at a 1:1 ratio using propensity score matching (PSM). Image data processing and visualization were performed using R software (version 4.2.3) and the ggplot2 package (version 3.3.5), respectively.

Results

Baseline characteristics

From January 2014 to December 2015, a total of 685 patients were included in this study, of whom 306 underwent sublobar resection VATS, and 379 underwent lobectomy VATS. The baseline clinical characteristics of the two groups are shown in Table 1. No significant differences in age, body mass index (BMI), sex, smoking status, drinking status, comorbidities, ASA status, differentiation grade, pathological type, tumor-node-metastasis (TNM) classification, multi-primary status, forced expiratory volume in 1 second (FEV₁), forced vital capacity (FVC), and nodal dissection were observed between the two groups. After 1:1 PSM, the data of 458 patients (229 pairs) were analyzed (Table 2).

Before PSM, significant differences were observed between the two groups in terms of tumor diameter (P=0.003) and CTR (P<0.001). After 1:1 PSM, the distribution of all variables was well balanced between the two groups (P>0.05).

Postoperative outcomes and complications

As shown in Table 3, significant differences were observed between the two groups in terms of operative time (sublobar resection: 100.71±47.24 minutes vs. lobectomy: 110.84±34.88 minutes, P=0.002), drainage duration (sublobar resection: 3.70±1.31 days vs. lobectomy: 4.47±2.44 days, P<0.001), and drainage volume (sublobar resection: 566.70±313.29 mL vs. lobectomy: 715.58±494.31 mL, P<0.001). The R0 resection rate was 100% in both groups, and no patients required conversion to open surgery.

After 1:1 PSM, the data of 458 patients (229 pairs) were analyzed. As shown in Table 4, significant differences were observed between the two groups in terms of drainage duration (sublobar resection: 3.72±1.33 days vs. lobectomy: 4.50±2.53 days, P=0.002) and drainage volume (sublobar resection: 572.88±304.18 mL vs. lobectomy: 712.07±551.39 mL, P=0.005). The overall complication rates were similar between the two groups. No significant differences in postoperative complications were observed between the two groups.

Survival outcomes

A total of 34 patients died and 49 patients developed recurrence or metastasis in the entire cohort. However, only seven patients died of lung cancer; the causes of death in other patients included other primary cancers, cerebral infarction, myocardial infarction, and accidents. The 10-year OS and RFS rates in the sublobar resection group were 96.7% and 94.4%, respectively, compared with 93.7% and 91.6% in the lobectomy group. No significant differences in 10-year OS [hazard ratio (HR) =0.51, 95% confidence interval (CI): 0.24–1.07, P=0.07] or 10-year RFS (HR =0.65, 95% CI: 0.36–1.16, P=0.14) were observed between the two groups (Figure 2A,2B). After 1:1 PSM, the results were similar between the groups: no significant differences were observed in 10-year OS (HR =0.87, 95% CI: 0.32–2.41, P=0.79) or 10-year RFS (HR =0.99, 95% CI: 0.45–2.21, P=0.99). No significant differences in prognosis were observed between the sublobar resection and lobectomy groups (Figure 2C,2D).

Figure 2 OS and RFS results. (A) The 10-year OS results before matching; (B) the 10-year RFS results before matching; (C) the 10-year OS results after matching; (D) the 10-year RFS results after matching. CI, confidence interval; HR, hazard ratio; OS, overall survival; RFS, recurrence-free survival.

Multivariable Cox proportional analysis for OS and RFS

The univariate Cox analysis revealed that advanced age, larger tumor diameter, poorer pathological prognosis, poorer differentiation, and higher CTR were significant factors associated with both OS and RFS (Figure 3). The multivariate Cox analysis showed that advanced age (HR =5.59, 95% CI: 1.89–16.56, P=0.002), poorer pathological prognosis (HR =3.89, 95% CI: 1.69–13.62, P=0.02), and higher CTR (HR =4.99, 95% CI: 2.73–45.67, P=0.02) were significant factors for OS (Figure 4). No significant differences in OS and RFS were observed between the sublobar resection and lobectomy groups. The 10-year OS (HR =1.05, 95% CI: 0.48–3.76, P=0.58) and 10-year RFS (HR =1.05, 95% CI: 0.47–2.36, P=0.89) did not differ significantly between the two groups.

Figure 3 Univariate analysis results. (A) Univariate analysis of OS; (B) univariate analysis of RFS. CI, confidence interval; CTR, consolidation-to-tumor ratio; OS, overall survival; RFS, recurrence-free survival; TNM, tumor-node-metastasis.

Figure 4 Multivariable analysis results. (A) Multivariable analysis of OS; (B) Multivariable analysis of RFS. CI, confidence interval; CTR, consolidation-to-tumor ratio; OS, overall survival; RFS, recurrence-free survival; TNM, tumor-node-metastasis.

Discussion

In another clinical trial (JCOG1211), segmentectomy achieved favorable survival outcomes in patients with GGO-predominant NSCLC measuring <3 cm in tumor diameter and with a CTR ≤0.5 (17). However, it remains unclear whether there are differences in long-term OS and RFS, as well as short-term perioperative outcomes and postoperative complications, between sublobar resection and lobectomy for GGO-predominant NSCLC with a CTR >0.5, or even for solid nodules. The present study sought to address this gap in the literature.

This study demonstrated that for patients with a tumor size ≤3 cm and a CTR ≤1, sublobar resection achieved long-term survival outcomes, including OS and RFS outcomes, comparable to those of lobectomy. However, the perioperative outcomes of the sublobar resection group were significantly better than those of the lobectomy group. After PSM, and following adjustment for baseline clinical characteristics, no significant differences were observed in long-term OS or RFS between the two groups; however, sublobar resection showed advantages in short-term perioperative indicators, including shorter drainage time and lower drainage volume. Compared with conventional lobectomy, intentional sublobar resection for GGO lesions ≤3 cm, including solid nodules, can improve perioperative outcomes while achieving comparable long-term survival outcomes. In addition, the sublobar resection group included wedge resections, which explains why the operative time was shorter in this group compared with the lobectomy group.

Findings from the JCOG0802/WJOG4607L trial indicated that for patients with peripheral adenocarcinoma (tumor size ≤2 cm and CTR between 0.5 and 1, excluding 0.5), segmentectomy provided superior OS compared with lobectomy, but no significant difference in RFS was observed (14,19). However, a 10-year follow-up of the JCOG0802 trial revealed that segmentectomy was associated with higher RFS than lobectomy, with no significant difference in OS between the two surgical approaches (16). These findings suggest that with longer follow-up, lobectomy may be associated with superior RFS compared with sublobar resection. However, in our study, no significant differences were observed in either long-term OS or RFS between the two surgical approaches.

Long-term follow-up results from a randomized controlled trial (CALGB140503) and JCOG0201 trial showed a 10-year OS rate of 80.3% and 94.0% (17,22). In the JCOG0804 study, the 5-year RFS rate was 99.7% and the 10-year RFS rate was 98.6% in these patients underwent sublobar resection, with no significant differences observed in 5-year RFS and 10-year RFS (23,24). This may be because lobectomy can achieve more adequate surgical margins. Wedge resection and segmentectomy are associated with certain disadvantages compared to lobectomy in this regard (RFS) (25,26). However, Moon et al. reported that surgical margin was not a significant prognostic factor for survival in patients with lung cancer (27,28).

In the present study, the univariate analysis identified advanced age, tumor size, and the CTR as potential risk factors. In the Multivariable analysis, both advanced age and the CTR remained important risk factors for OS and RFS. Patients with GGOs and a CTR ≤0.5 generally demonstrate favorable long-term survival outcomes (29-31). However, in the present study, no significant differences in OS and RFS were observed between the patients with GGOs and a CTR >0.5 who underwent sublobar resection or lobectomy.

This study had several limitations inherent to its retrospective design, including an insufficient sample size, lack of randomization, and potential bias. Future multi-center prospective studies are warranted to validate these findings. Because these tumors have fundamentally different biological behaviors and prognoses, analyzing them as a single pooled cohort severely dilutes the results. Notably, the sample size of our current single-center dataset is relatively limited, which further restricts the reliability and generalizability of the statistical outcomes. Future research should adopt a multicenter prospective design to accumulate larger patient populations. Stratified subgroup analyses based on tumor pathological subtypes and clinical characteristics will be conducted to eliminate confounding biases and yield more robust, interpretable conclusions.

Conclusions

Compared with conventional lobectomy, intentional sublobar resection for GGOs with a tumor size ≤3 cm, including solid nodules, may improve perioperative outcomes while achieving comparable long-term survival 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-2026-1486/rc

Data Sharing Statement: Available at https://jtd.amegroups.com/article/view/10.21037/jtd-2026-1486/dss

Peer Review File: Available at https://jtd.amegroups.com/article/view/10.21037/jtd-2026-1486/prf

Funding: This work was supported by the Research Fund for Basic Research of Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University (No. 2022RC178) entitled “Mechanism of GREM1 in regulating DNA damage repair in esophageal cancer via inhibiting the PTEN signaling pathway”.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-2026-1486/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 ethics board of Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University (No. 2026225701) and individual consent for this retrospective analysis was waived.

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. Sung H, Ferlay J, Siegel RL, et al. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin 2021;71:209-49. [Crossref] [PubMed]
2. Bertolaccini L, Tralongo AC, Del Re M, et al. Segmentectomy vs. Lobectomy in stage IA non-small cell lung cancer: A systematic review and meta-analysis of perioperative and survival outcomes. Lung Cancer 2024;197:107990.
3. Aberle DR, Adams AM, et al. Reduced lung-cancer mortality with low-dose computed tomographic screening. N Engl J Med 2011;365:395-409.
4. Torre LA, Siegel RL, Ward EM, et al. Global Cancer Incidence and Mortality Rates and Trends--An Update. Cancer Epidemiol Biomarkers Prev 2016;25:16-27. [Crossref] [PubMed]
5. Oudkerk M, Liu S, Heuvelmans MA, et al. Lung cancer LDCT screening and mortality reduction - evidence, pitfalls and future perspectives. Nat Rev Clin Oncol 2021;18:135-51. [Crossref] [PubMed]
6. Sihoe ADL, Cardillo G. Solitary pulmonary ground-glass opacity: is it time for new surgical guidelines? Eur J Cardiothorac Surg 2017;52:848-51. [Crossref] [PubMed]
7. Ginsberg RJ, Rubinstein LV. Randomized trial of lobectomy versus limited resection for T1 N0 non-small cell lung cancer. Lung Cancer Study Group. Ann Thorac Surg 1995;60:615-22; discussion 622-3.
8. Matsuoka Y, Yurugi Y, Takagi Y, et al. Prognostic Significance of Solid and Micropapillary Components in Invasive Lung Adenocarcinomas Measuring ≤3 cm. Anticancer Res 2016;36:4923-30. [Crossref] [PubMed]
9. Blasberg JD, Pass HI, Donington JS. Sublobar resection: a movement from the Lung Cancer Study Group. J Thorac Oncol 2010;5:1583-93. [Crossref] [PubMed]
10. Shimizu K, Yamada K, Saito H, et al. Surgically curable peripheral lung carcinoma: correlation of thin-section CT findings with histologic prognostic factors and survival. Chest 2005;127:871-8. [Crossref] [PubMed]
11. Takashima S, Maruyama Y, Hasegawa M, et al. CT findings and progression of small peripheral lung neoplasms having a replacement growth pattern. AJR Am J Roentgenol 2003;180:817-26. [Crossref] [PubMed]
12. 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]
13. Hattori A, Hirayama S, Matsunaga T, et al. Distinct Clinicopathologic Characteristics and Prognosis Based on the Presence of Ground Glass Opacity Component in Clinical Stage IA Lung Adenocarcinoma. J Thorac Oncol 2019;14:265-75. [Crossref] [PubMed]
14. 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]
15. Katsumata S, Aokage K, Ishii G, et al. Pathological features and prognostic implications of ground-glass opacity components on computed tomography for clinical stage I lung adenocarcinoma. Surg Today 2021;51:1188-202. [Crossref] [PubMed]
16. Hattori A, Suzuki K, Takamochi K, et al. Segmentectomy versus lobectomy in small-sized peripheral non-small-cell lung cancer with radiologically pure-solid appearance in Japan (JCOG0802/WJOG4607L): a post-hoc supplemental analysis of a multicentre, open-label, phase 3 trial. Lancet Respir Med 2024;12:105-16. [Crossref] [PubMed]
17. 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]
18. Mimae T, Saji H, Nakamura H, et al. Survival of Octogenarians with Early-Stage Non-small Cell Lung Cancer is Comparable Between Wedge Resection and Lobectomy/Segmentectomy: JACS1303. Ann Surg Oncol 2021;28:7219-27. [Crossref] [PubMed]
19. Altorki N, Wang X, Kozono D, et al. Lobar or Sublobar Resection for Peripheral Stage IA Non-Small-Cell Lung Cancer. N Engl J Med 2023;388:489-98. [Crossref] [PubMed]
20. Phillips WW, Gill RR, Mazzola E, et al. Impact of Nodule Density in Women With Sublobar Resection for Stage IA Adenocarcinoma. Ann Thorac Surg 2021;112:1067-75. [Crossref] [PubMed]
21. Kakinuma R, Noguchi M, Ashizawa K, et al. Natural History of Pulmonary Subsolid Nodules: A Prospective Multicenter Study. J Thorac Oncol 2016;11:1012-28. [Crossref] [PubMed]
22. Rajaram R, Huang Q, Li RZ, et al. Recurrence-Free Survival in Patients With Surgically Resected Non-Small Cell Lung Cancer: A Systematic Literature Review and Meta-Analysis. Chest 2024;165:1260-70. [Crossref] [PubMed]
23. Mamede I, Ribeiro L, Stecca C, et al. Survival and pulmonary function in stage IA non-small cell lung cancer after sublobar resection versus lobectomy: An updated meta-analysis. J Surg Oncol 2024;130:523-32. [Crossref] [PubMed]
24. Zhang C, Pan Y, Li H, et al. Extent of surgical resection for radiologically subsolid T1N0 invasive lung adenocarcinoma: When is a wedge resection acceptable?. J Thorac Cardiovasc Surg 2024;167:797-809.e2. [Crossref] [PubMed]
25. El-Sherif A, Fernando HC, Santos R, et al. Margin and local recurrence after sublobar resection of non-small cell lung cancer. Ann Surg Oncol 2007;14:2400-5. [Crossref] [PubMed]
26. Li T, He W, Zhang X, et al. Survival outcomes of segmentectomy and lobectomy for early stage non-small cell lung cancer: a systematic review and meta-analysis. J Cardiothorac Surg 2024;19:353. [Crossref] [PubMed]
27. Moon Y, Lee KY, Moon SW, et al. Sublobar Resection Margin Width Does Not Affect Recurrence of Clinical N0 Non-small Cell Lung Cancer Presenting as GGO-Predominant Nodule of 3 cm or Less. World J Surg 2017;41:472-9. [Crossref] [PubMed]
28. Pan H, Chen H, Ge Z, et al. Lobectomy Versus Sub-lobectomy for Clinical Stage IA (≤2 cm) Lung Squamous Cell Carcinoma with Tumour Spread through Air Spaces: A Multi-Centre Retrospective Study. Eur J Cardiothorac Surg 2025;67:ezaf224. [Crossref] [PubMed]
29. Liu C, Yang Z, Li Y, et al. Intentional wedge resection versus segmentectomy for ≤2 cm ground-glass-opacity-dominant non-small cell lung cancer: a real-world study using inverse probability of treatment weighting. Int J Surg 2024;110:4231-9. [Crossref] [PubMed]
30. Nitadori J, Bograd AJ, Kadota K, et al. Impact of micropapillary histologic subtype in selecting limited resection vs lobectomy for lung adenocarcinoma of 2cm or smaller. J Natl Cancer Inst 2013;105:1212-20. [Crossref] [PubMed]
31. 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]

(English Language Editor: L. Huleatt)