Comparison of surgery and stereotactic body radiation therapy for clinical stage I NSCLC: a propensity score-matched analysis from a single institution

Introduction

The standard treatment for clinical stage I non-small cell lung cancer (NSCLC) is lobectomy with mediastinal lymph node dissection (1,2). However, for patients who are medically inoperable or who decline surgery for personal reasons, stereotactic body radiation therapy (SBRT) has emerged as an effective alternative. Several studies have shown that SBRT provides treatment outcomes comparable to those of surgery (3,4).

Based on these findings, some studies have attempted to evaluate whether SBRT can be an alternative to surgery, even in operable patients. However, because surgery is the established standard treatment based on strong clinical evidence, randomized controlled trials (RCTs) assigning operable patients to SBRT arms have faced difficulties in patient recruitment, leading to early closure of trials such as STARS and ROSEL (5,6). While a pooled analysis of these trials showed equivalent outcomes between SBRT and surgery, the small sample size and short follow-up limited the strength of the conclusions (5). A rigorously designed RCT comparing SBRT and surgery is ongoing, and its results are expected to provide stronger evidence for comparison between the two modalities (7,8).

Large retrospective cohort studies using propensity score matching (PSM) to adjust for confounding factors tend to report better outcomes for surgery (9,10). Meta-analyses of these retrospective studies have shown similar trends (11,12). However, these studies still have inherent limitations due to residual confounding and selection bias.

Most patients diagnosed with clinical stage I NSCLC opt for surgery when it is feasible. Nonetheless, elderly patients or those with impaired performance status or reduced cardiopulmonary function may hesitate due to surgical risk and may consider SBRT. Although SBRT has the advantages of being less invasive and having a shorter recovery time than surgery, the uncertainty of its long-term outcomes remains a concern for physicians and patients (13).

Therefore, comparing the actual treatment outcomes of surgery and SBRT within a single institution may provide valuable information for patients to make informed decisions based on their clinical situation. This study aimed to compare the treatment outcomes of SBRT and the standard surgical procedure (lobectomy with mediastinal lymph node dissection) among patients with stage I NSCLC diagnosed at Ajou University Hospital, using PSM to adjust for confounding variables. We present this article in accordance with the STROBE reporting checklist (available at https://jtd.amegroups.com/article/view/10.21037/jtd-2025-925/rc).

Methods

We conducted a retrospective review of patients with clinical stage I NSCLC diagnosed at Ajou University Hospital between 2016 and 2021, according to the American Joint Committee on Cancer (AJCC) 8th edition staging system. Patients who had a history of other malignancies within the past five years or had double primary lung cancers been excluded. The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. This study was approved by the Institutional Review Board of Ajou University Hospital (No. AJOUIRB-MDB-2022-241), and the requirement for informed consent was waived due to the retrospective nature of the study.

Patients who underwent lobectomy with mediastinal lymph node dissection as their initial treatment were assigned to the surgery group. We defined central tumors as those within 2 cm of the proximal bronchial tree. We performed SBRT only when we could secure a safe margin from the bronchial wall. When we achieved an adequate margin, we delivered 48 Gy in 4 fractions; otherwise, we used 40 Gy in 4 fractions, following our institutional protocol.

Surgery was performed under general anesthesia through either thoracotomy or video-assisted thoracoscopic surgery (VATS). Systematic lymph node dissection included at least three mediastinal and one hilar lymph node station. All lymph nodes were pathologically assessed, and surgical margins were confirmed macroscopically and microscopically negative.

SBRT planning was performed using 4D-CT to account for respiratory motion. An internal target volume (ITV) was defined, and a 5 mm isotropic margin was added to generate the planning target volume (PTV). Treatment was delivered using volumetric modulated arc therapy (VMAT) with 6–10 MV photon beams, and daily image guidance with cone-beam CT was performed before each fraction.

We used the nearest neighbor method to minimize selection bias and performed 1:3 PSM between the SBRT and surgery groups. Matching variables included age, sex, histologic subtype, T stage, and tumor location.

Statistical analysis

For comparisons of clinical characteristics and patterns of failure, the t-test was used for continuous variables and the chi-square test for categorical variables. Overall survival (OS) and disease-free survival (DFS) were estimated using the Kaplan-Meier method, and comparisons between groups were made using the log-rank test. Hazard ratios (HRs) for survival were estimated using Cox proportional hazards models. A P value <0.05 was considered statistically significant. All analyses were performed using R statistical software (R Foundation, Vienna, Austria; https://www.r-project.org).

The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. This study was approved by the Institutional Review Board of Ajou University Hospital (No. AJOUIRB-MDB-2022-241), and the requirement for informed consent was waived due to the retrospective nature of the study.

Results

From January 2016 to December 2021, 249 patients were diagnosed with clinical stage I NSCLC at Ajou University Hospital, of whom 44 were treated with SBRT and 205 underwent surgery. The median follow-up durations were 34.9 months for the SBRT group and 24.1 months for the surgery group.

After excluding 17 patients with prior malignancies, 4 with double primary lung cancers, and additional patients with incomplete data, 214 patients were finally included in the analysis. PSM (1:3) resulted in 31 patients in the SBRT group and 93 in the surgery group (Figure 1).

Figure 1 Flow diagram of patient selection. A total of 249 patients with clinical stage I NSCLC were identified, including 44 treated with SBRT and 205 with lobectomy. After excluding those with a prior cancer diagnosis within 5 years, the cases of double primary lung cancer and additional patients with incomplete data, 214 patients remained for analysis (SBRT, n=31; lobectomy, n=183). NSCLC, non-small cell lung cancer; SBRT, stereotactic body radiation therapy.

Baseline characteristics before and after matching are summarized in Table 1. Before matching, the groups had significant differences in age and histologic subtype. After matching, age remained significantly different (mean age: SBRT 79.6 years vs. surgery 72.7 years, P<0.001).

In the surgery group, 15 patients (16.0%) were found to have pathologically positive lymph nodes, and 17 patients (18.3%) received adjuvant chemotherapy.

There was no significant difference in OS between the groups before matching (3-year OS: 90.0% vs. 93.0%, P=0.38) (Figure 2A) or after matching (3-year OS: 90.0% vs. 90.7%, P=0.90) (Figure 2B). However, DFS was significantly better in the surgery group before and after matching (pre-PSM: 3-year DFS 54.5% vs. 78.1%, P<0.001; post-PSM: 54.4% vs. 68.2%, P=0.03) (Figure 2C,2D). Locoregional recurrence-free survival was significantly higher in the surgery group (P=0.02) (Figure 3A), while there was no significant difference in distant recurrence-free survival between the groups (P=0.99) (Figure 3B).

Figure 2 Overall and disease-free survival before and after PSM. (A) Overall survival before PSM. (B) Overall survival after PSM. (C) Disease-free survival before PSM. (D) Disease-free survival after PSM. CI, confidence interval; HR, hazard ratio; PSM, propensity score matching; SBRT, stereotactic body radiation therapy.

Figure 3 Locoregional recurrence-free and distant metastasis-free survival after PSM. (A) Locoregional RFS. (B) Distant metastasis-free survival. CI, confidence interval; HR, hazard ratio; PSM, propensity score matching; RFS, recurrence-free survival; SBRT, stereotactic body radiation therapy.

Patterns of failure are summarized in Table 2. Local recurrence occurred in 6 patients (19.4%) of patients in the SBRT group and 0% in the surgery group (P<0.001). Among SBRT patients, 27 received 48 Gy, and 4 received 40 Gy in 4 fractions. Local recurrence occurred in 5 patients from the 48 Gy group and 1 from the 40 Gy group, with no significant difference between SBRT dose regimens (Fisher’s exact test, P>0.99). Regional and distant recurrence rates did not differ significantly between groups. No grade 4 or 5 adverse events were observed in either group.

Discussion

This study is a retrospective analysis comparing the treatment outcomes of surgery and SBRT in patients with clinical stage I NSCLC at a single institution. PSM was used to adjust for confounding variables. The results showed no significant difference in OS or distant metastasis rate between the two groups. However, DFS and local recurrence rate were significantly better in the surgery group.

The higher local recurrence rate observed in the SBRT group may be due to the inability of radiotherapy to completely remove the tumor, in contrast to surgical resection (14). In particular, some SBRT protocols used in this study applied relatively conservative radiation doses, which may have led to insufficient biologically effective dose (BED) for tumor control. When assuming an α/β ratio of 10 Gy for NSCLC, a BED ≥100 Gy is generally associated with improved local control (15). Although the 48 Gy in 4 fractions protocol used in our institution exceeds this threshold, the 40 Gy in 4 fractions protocol does not. Furthermore, the latter was often applied in patients with poorer general conditions, which may have negatively influenced treatment efficacy. Nevertheless, our findings showed no significant difference in local recurrence between the 48 and 40 Gy groups, indicating that reduced dosing may still be acceptable in carefully selected patients with central tumors.

The local control rate in our SBRT group was lower than those reported in previous studies, which have shown control rates of 85–90% in early-stage NSCLC (16,17). This difference may be attributable to the small sample size, the inclusion of central tumors for which dose reduction was applied, and the generally poorer performance status of patients selected for SBRT in our cohort.

Despite the higher local recurrence rate, the comparable OS in the SBRT group is noteworthy (18). This may be explained by effective salvage treatments for local recurrence (19,20) or by avoidance of surgery-related short-term morbidity and mortality (21,22). SBRT is a non-invasive treatment with lower acute risk compared to surgery. Moreover, the SBRT group in this study consisted of older and potentially frailer patients, which makes the survival outcome even more clinically meaningful (23). In contrast to surgery, SBRT avoids perioperative morbidity, which may be particularly beneficial in older or high-risk patients.

On the other hand, surgery offers several significant advantages. First, mediastinal lymph node dissection allows pathological evaluation of clinically negative lymph nodes (1). In this study, 16% of patients in the surgery group were found to have pathologically positive lymph nodes, and 18.3% received adjuvant chemotherapy based on these findings. Surgical resection thus facilitates accurate pathological staging and enables further treatment planning. In contrast, SBRT does not allow for pathological confirmation of lymph node status, which limits the ability to deliver adjuvant therapy when needed (1).

Nevertheless, the two groups had no statistically significant difference in regional or distant recurrence rates. These findings suggest that SBRT can still provide a certain level of disease control, even without pathologic lymph node evaluation. Further research on adjuvant systemic therapies is warranted to enhance the effectiveness of SBRT, especially in patients with high-risk features such as large tumor size, genetic mutations, or high programmed cell death-ligand 1 (PD-L1) expression. In this context, the potential roles of cytotoxic chemotherapy, targeted therapy, and immunotherapy warrant investigation (24,25).

Recently, several clinical trials have been actively investigating the role of immunotherapy following SBRT or surgery in early-stage NSCLC. These include a study comparing adjuvant pembrolizumab versus observation after curative resection for stage I NSCLC (NCT04317534) (26), the PACIFIC-4 (RTOG 3515) trial evaluating adjuvant durvalumab following SBRT (27), and the KEYNOTE-867 trial assessing the efficacy and safety of concurrent and maintenance pembrolizumab with SBRT (28). These studies highlight the potential of combining immunotherapy with local treatments and may support the development of effective multimodal strategies in this setting.

This study has several limitations, including its retrospective design at a single institution, which may limit generalizability. The sample size was relatively small, and the follow-up period was not long enough to fully assess long-term outcomes. Although PSM was used to reduce confounding, age remained significantly different between the two groups after matching. This reflects real-world differences in patient selection between SBRT and surgery in clinical practice (23). Additionally, we used a 3:1 PSM approach to optimize statistical power and better utilize the larger control cohort. However, this method may increase the risk of poorer covariate balance and lead to the exclusion of unmatched patients, which may reduce the generalizability of our findings. Nonetheless, the comparable OS in the SBRT group supports its potential role as an alternative to surgery, particularly in elderly or high-risk patients. We did not define a separate clinical target volume (CTV) but applied a direct margin from gross target volume (i.e., ITV) to PTV. While this approach reflects real-world SBRT protocols, it may limit the ability to analyze the impact of target volume on treatment outcomes.

Further prospective randomized trials are needed to provide more definitive evidence comparing SBRT and surgery in operable stage I NSCLC. Such trials are currently underway, and their results will help clarify indications and guide treatment selection between the two approaches (7,8).

Conclusions

Our findings suggest that while SBRT showed a higher rate of local recurrence compared to surgery, OS and distant recurrence outcomes were comparable in patients with clinical stage I NSCLC. Given its non-invasive nature, SBRT may be a reasonable alternative for elderly patients or those at high surgical risk. However, these results should be interpreted with caution due to the small number of patients treated with SBRT. Further research with larger cohorts and longer follow-up is warranted to validate these findings and explore the role of adjuvant therapies.

Acknowledgments

None.

Footnote

Reporting Checklist: The authors have completed the STROBE reporting checklist. Available at https://jtd.amegroups.com/article/view/10.21037/jtd-2025-925/rc

Data Sharing Statement: Available at https://jtd.amegroups.com/article/view/10.21037/jtd-2025-925/dss

Peer Review File: Available at https://jtd.amegroups.com/article/view/10.21037/jtd-2025-925/prf

Funding: None.

Conflicts of Interest: Both authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-2025-925/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. This study was approved by the Institutional Review Board of Ajou University Hospital (No. AJOUIRB-MDB-2022-241), and the requirement for informed consent was waived due to the retrospective nature of 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. 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.
2. Riely GJ, Wood DE, Ettinger DS, et al. Non-Small Cell Lung Cancer, Version 4.2024, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw 2024;22:249-74. [Crossref] [PubMed]
3. Timmerman R, Paulus R, Galvin J, et al. Stereotactic body radiation therapy for inoperable early stage lung cancer. JAMA 2010;303:1070-6. [Crossref] [PubMed]
4. Chang JY, Mehran RJ, Feng L, et al. Stereotactic ablative radiotherapy for operable stage I non-small-cell lung cancer (revised STARS): long-term results of a single-arm, prospective trial with prespecified comparison to surgery. Lancet Oncol 2021;22:1448-57. [Crossref] [PubMed]
5. Chang JY, Senan S, Paul MA, et al. Stereotactic ablative radiotherapy versus lobectomy for operable stage I non-small-cell lung cancer: a pooled analysis of two randomised trials. Lancet Oncol 2015;16:630-7. [Crossref] [PubMed]
6. Franks KN, McParland L, Webster J, et al. SABRTooth: a randomised controlled feasibility study of stereotactic ablative radiotherapy (SABR) with surgery in patients with peripheral stage I nonsmall cell lung cancer considered to be at higher risk of complications from surgical resection. Eur Respir J 2020;56:2000118. [Crossref] [PubMed]
7. Teke ME, Sarvestani AL, Hernandez JM, et al. A Randomized, Phase III Study of Sublobar Resection (SR) Versus Stereotactic Ablative Radiotherapy (SAbR) in High-Risk Patients with Stage I Non-Small Cell Lung Cancer (NSCLC). Ann Surg Oncol 2022;29:4686-7. [Crossref] [PubMed]
8. Ritter TA, Timmerman RD, Hanfi HI, et al. Centralized Quality Assurance of Stereotactic Body Radiation Therapy for the Veterans Affairs Cooperative Studies Program Study Number 2005: A Phase 3 Randomized Trial of Lung Cancer Surgery or Stereotactic Radiotherapy for Operable Early-Stage Non-Small Cell Lung Cancer (VALOR). Pract Radiat Oncol 2025;15:e29-39. [Crossref] [PubMed]
9. Rosen JE, Salazar MC, Wang Z, et al. Lobectomy versus stereotactic body radiotherapy in healthy patients with stage I lung cancer. J Thorac Cardiovasc Surg 2016;152:44-54.e9. [Crossref] [PubMed]
10. Bryant AK, Mundt RC, Sandhu AP, et al. Stereotactic Body Radiation Therapy Versus Surgery for Early Lung Cancer Among US Veterans. Ann Thorac Surg 2018;105:425-31. [Crossref] [PubMed]
11. Cao C, Wang D, Chung C, et al. A systematic review and meta-analysis of stereotactic body radiation therapy versus surgery for patients with non-small cell lung cancer. J Thorac Cardiovasc Surg 2019;157:362-373.e8. [Crossref] [PubMed]
12. Viani GA, Gouveia AG, Yan M, et al. Stereotactic body radiotherapy versus surgery for early-stage non-small cell lung cancer: an updated meta-analysis involving 29,511 patients included in comparative studies. J Bras Pneumol 2022;48:e20210390. [Crossref] [PubMed]
13. Yuan XS, Chen WC, Lin QR, et al. A propensity-matched analysis of stereotactic body radiotherapy and sublobar resection for stage I non-small cell lung cancer in patients at high risk for lobectomy: the results in a Chinese population. J Thorac Dis 2021;13:1822-32. [Crossref] [PubMed]
14. Crabtree TD, Puri V, Robinson C, et al. Analysis of first recurrence and survival in patients with stage I non-small cell lung cancer treated with surgical resection or stereotactic radiation therapy. J Thorac Cardiovasc Surg 2014;147:1183-1191; discussion 1191-2. [Crossref] [PubMed]
15. Onishi H, Shirato H, Nagata Y, et al. Hypofractionated stereotactic radiotherapy (HypoFXSRT) for stage I non-small cell lung cancer: updated results of 257 patients in a Japanese multi-institutional study. J Thorac Oncol 2007;2:S94-100. [Crossref] [PubMed]
16. Swaminath A, Wierzbicki M, Parpia S, et al. Canadian Phase III Randomized Trial of Stereotactic Body Radiotherapy Versus Conventionally Hypofractionated Radiotherapy for Stage I, Medically Inoperable Non-Small-Cell Lung Cancer - Rationale and Protocol Design for the Ontario Clinical Oncology Group (OCOG)-LUSTRE Trial. Clin Lung Cancer 2017;18:250-4. [Crossref] [PubMed]
17. Bezjak A, Paulus R, Gaspar LE, et al. Safety and Efficacy of a Five-Fraction Stereotactic Body Radiotherapy Schedule for Centrally Located Non-Small-Cell Lung Cancer: NRG Oncology/RTOG 0813 Trial. J Clin Oncol 2019;37:1316-25. [Crossref] [PubMed]
18. Henschke CI, Yip R, Sun Q, Li P, Kaufman A, Samstein R, Connery C, Kohman L, Lee P, Tannous H, Yankelevitz DF, Taioli E, Rosenzweig K, Flores RM. I-ELCAP; IELCART Investigators. Prospective Cohort Study to Compare Long-Term Lung Cancer-Specific and All-Cause Survival of Clinical Early Stage (T1a-b; ≤20 mm) NSCLC Treated by Stereotactic Body Radiation Therapy and Surgery. J Thorac Oncol 2024;19:476-90. [Crossref] [PubMed]
19. Brooks ED, Verma V, Senan S, et al. Salvage Therapy for Locoregional Recurrence After Stereotactic Ablative Radiotherapy for Early-Stage NSCLC. J Thorac Oncol 2020;15:176-89. [Crossref] [PubMed]
20. Afshari S, Anker CJ, Kooperkamp HZ, et al. Trends and Outcomes of Salvage Lobectomy for Early-stage Non-Small Cell Lung Cancer. Am J Clin Oncol 2023;46:271-5. [Crossref] [PubMed]
21. Yu JB, Soulos PR, Cramer LD, et al. Comparative effectiveness of surgery and radiosurgery for stage I non-small cell lung cancer. Cancer 2015;121:2341-9. [Crossref] [PubMed]
22. Stokes WA, Bronsert MR, Meguid RA, et al. Post-Treatment Mortality After Surgery and Stereotactic Body Radiotherapy for Early-Stage Non-Small-Cell Lung Cancer. J Clin Oncol 2018;36:642-51. [Crossref] [PubMed]
23. Jang JK, Atay SM, Ding L, et al. Patterns of Use of Stereotactic Body Radiation Therapy Compared With Surgery for Definitive Treatment of Primary Early-stage Non-small Cell Lung Cancer. Am J Clin Oncol 2022;45:146-54. [Crossref] [PubMed]
24. Tsutani Y, Imai K, Ito H, et al. Adjuvant Chemotherapy for High-risk Pathologic Stage I Non-Small Cell Lung Cancer. Ann Thorac Surg 2022;113:1608-16. [Crossref] [PubMed]
25. Felip E, Altorki N, Zhou C, et al. Adjuvant atezolizumab after adjuvant chemotherapy in resected stage IB-IIIA non-small-cell lung cancer (IMpower010): a randomised, multicentre, open-label, phase 3 trial. Lancet 2021;398:1344-57. [Crossref] [PubMed]
26. A Randomized Phase II Trial of Adjuvant Pembrolizumab Versus Observation Following Curative Resection for Stage I Non-small Cell Lung Cancer (NSCLC) With Primary Tumors Between 1-4 cm: Big Ten Cancer Research Consortium BTCRC-LUN18-153. 2020. Available online: https://clinicaltrials.gov/study/NCT04317534
27. A Phase III, Randomized, Placebo-controlled, Double-blind, Multi-center, International Study of Durvalumab With Stereotactic Body Radiation Therapy (SBRT) for the Treatment of Patients With Unresected Stage I/II, Lymph-node Negative Non-small Cell Lung Cancer (PACIFIC-4/RTOG-3515) Osimertinib Following SBRT, a Single Arm Cohort for Patients With Unresected Stage I/II, Lymph Node Negative NSCLC Harboring a Sensitizing EGFR Mutation. 2019. Available online: https://clinicaltrials.gov/study/NCT03833154
28. A Phase 3, Randomized, Placebo-Controlled Clinical Study to Evaluate the Safety and Efficacy of Stereotactic Body Radiotherapy (SBRT) With or Without Pembrolizumab (MK-3475) in Participants With Unresected Stages I or II Non Small Cell Lung Cancer (NSCLC) (KEYNOTE-867). 2019. Available online: https://clinicaltrials.gov/study/NCT03924869