Role of postoperative adjuvant targeted therapy in survival outcomes after sublobar resection in patients with EGFR-mutated stageⅠ (T≤3 cm) invasive lung adenocarcinoma: A retrospective cohort study_Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

Authors：

HUANG Zhaokang , CAO Jie , LIU Zetao , LIAO Xizhou , ZONG Xiaorong , LI Peidi , GUO Chenglin ,  MEI Jiandong

Department of Thoracic Surgery, West China Hospital, Sichuan University, Chengdu, 610041, P. R. China;

Corresponding?author：

MEI Jiandong, Email: sureman2003congo@163.com

Keywords：

Lung adenocarcinoma; epidermal growth factor receptor (EGFR) mutation; sublobar resection; targeted therapy; inverse probability of treatment weighting; survival analysis

DOI：

10.7507/1007-4848.202602073

Video：

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Objective To compare the survival outcomes in patients with epidermal growth factor receptor (EGFR)-mutated stageⅠ invasive lung adenocarcinoma who underwent lobectomy, sublobar resection, and sublobar resection plus postoperative targeted therapy, and to evaluate whether the combined strategy yield outcomes similar to lobectomy in a real-world setting. Methods This retrospective cohort study enrolled consecutive patients who underwent video-assisted thoracoscopic radical resection at West China Hospital, Sichuan University, between November 2017 and April 2025. All patients had postoperative pathologic stageⅠ invasive lung adenocarcinoma according to the 8th edition of the TNM stage, and confirmed EGFR mutations. Patients were categorized into three groups: a lobectomy alone group (lobectomy group), a sublobar resection alone group (sublobar resection group), and a sublobar resection plus postoperative targeted therapy group (combined group). Inverse probability of treatment weighting (IPTW) was applied to balance the baseline characteristics. Overall survival (OS) and recurrence-free survival (RFS), defined as time to first recurrence with death treated as censoring, were compared. Results A total of 450 patients was enrolled with 157 in the lobectomy group, 240 in the sublobar resection group, and 53 in the combined group. Among patients who did not receive any adjuvant therapy, OS was similar between the sublobar group and the lobectomy group, whereas sublobar resection had significantly poor RFS. In comparisons between the lobectomy group and the combined group, neither OS nor RFS differed significantly before or after IPTW adjustment. Conclusions Among patients with EGFR-mutated stageⅠ lung adenocarcinoma, sublobar resection is associated with poor RFS when compared with lobectomy. The combined strategy shows no statistically significant survival difference versus lobectomy. Prospective studies with rigorous design are warranted to further validate the above findings.

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2.	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(10335): 1607-1617.
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5.	Cho J, Kim J, Kim K, et al. Long-term outcomes of segmentectomy versus lobectomy for stage I lung adenocarcinoma: a nationwide cohort study. J Thorac Cardiovasc Surg, 2022, 164(6): 1705-1716.
6.	Zou J, Chen H, Fu F, et al. Sublobar resections for peripheral non-small cell lung cancer ≤2 cm: implications of randomized trials and remaining questions. Lung Cancer, 2024, 186: 107353.
7.	Tsuboi M, Herbst RS, Winton T, et al. Overall survival with osimertinib in resected EGFR-mutated NSCLC. N Engl J Med, 2023, 389(2): 137-147.
8.	Jiang Y, He X, Li W, et al. Adjuvant EGFR-TKI for resected EGFR-mutated non-small cell lung cancer: a systematic review and meta-analysis of randomized controlled trials. eClinicalMedicine, 2023, 64: 102205.
9.	Furuya N, Yamada T, Morita S, et al. Adjuvant osimertinib for resected EGFR-mutated stage IB-ⅢA NSCLC: updated disease-free survival and safety. J Clin Oncol, 2023, 41(15_suppl): 8500.
10.	Suzuki K, Watanabe S, Wakabayashi M, et al. A single-arm study of sublobar resection for ground-glass opacity dominant peripheral lung cancer (JCOG0804/WJOG4507L). J Thorac Cardiovasc Surg, 2022, 164(2): 289-301.
11.	Wu YL, John T, Grohe C, et al. Osimertinib in resected EGFR-mutated non-small-cell lung cancer: CNS disease recurrence and outcomes. J Clin Oncol, 2022, 40(21): e200-e210.
12.	Li N, Deng Y, Zhou X, et al. Driver mutation-positive stage I lung adenocarcinoma: clinicopathologic features and survival outcomes in a multicenter cohort. J Thorac Oncol, 2021, 16(11): 1893-1905.
13.	Yamashita S, Tokuishi K, Moroga T, et al. Pleural invasion and lymphovascular invasion predict recurrence after complete resection of stage I lung adenocarcinoma. Ann Surg Oncol, 2022, 29(9): 5565-5574.
14.	Kakugawa K, Murakawa T, Nakajima J, et al. Brief report: validation study of the IASLC histological grading system of invasive lung adenocarcinoma. J Thorac Oncol, 2021, 16(10): 1754-1759.
15.	Yotsukura M, Asamura H, Motoi N, et al. Visceral pleural invasion and micropapillary/solid components are associated with recurrence in stage I lung adenocarcinoma. J Thorac Oncol, 2022, 17(7): 932-942.
16.	Tsao MS, Nicholson AG, Maleszewski JJ, et al. IASLC/ATS/ERS classification and grading updates for lung adenocarcinoma: implications for prognosis and adjuvant therapy. J Thorac Oncol, 2021, 16(9): 1485-1486.
17.	Kadota K, Kushida Y, Kagawa S, et al. Spread through air spaces (STAS) is an independent predictor of recurrence in stage I lung adenocarcinoma after limited resection: a systematic review and meta-analysis. Lung Cancer, 2021, 156: 1-9.
18.	Feng T, Li J, He Y, et al. High-risk features associated with recurrence in stage I lung adenocarcinoma. J Thorac Cardiovasc Surg, 2024, 168(3): 781-789.
19.	Haruki T, Aokage K, Miyoshi T, et al. Visceral pleural invasion and STAS predict recurrence after sublobar resection for early-stage lung adenocarcinoma. Eur J Cardiothorac Surg, 2022, 61(4): 799-807.
20.	Brunelli A, Decaluwe H, Gonzalez M, et al. European Society of Thoracic Surgeons expert consensus recommendations on technical standards of segmentectomy for primary lung cancer. Eur J Cardiothorac Surg, 2023, 63(6): ezad224.
21.	Liu Y, Matsouaka RA, Thomas L, et al. A tutorial for propensity score weighting methods under violations of the positivity assumption. Stat Med, 2025, 44(5): 1011-1035.
22.	Zhou T, Tong G, Li F, et al. PSweight: An R package for propensity score weighting analysis. R J, 2022, 14(1): 282-300.
23.	Li F, Li F, Thomas LE. Addressing extreme propensity scores via the overlap weights. Am J Epidemiol, 2021, 190(12): 2507-2515.
24.	Yoshida K, Solomon DH, Kim SC, et al. Multinomial extension of propensity score trimming methods: a simulation study. Am J Epidemiol, 2021, 190(12): 2696-2705.
25.	Ciolino JD, Martin RH, Zhao W, et al. Reporting and interpreting causal inference analyses using propensity scores in clinical research. JAMA Netw Open, 2021, 4(6): e2111696.
26.	Wu YL, Tsuboi M, He J, et al. Osimertinib in resected EGFR-mutated non-small-cell lung cancer. N Engl J Med, 2020, 383(18): 1711-1723.
27.	Liu Z, Wang Y, Chen X, et al. Adjuvant EGFR-TKI therapy for pathologic stageⅠEGFR-mutated lung adenocarcinoma: a real-world study. Clin Lung Cancer, 2025, 26(1): e1-e10.
28.	Wang J, Li H, Zhang Y, et al. Adjuvant EGFR-TKI improves disease-free survival in high-risk stage IA lung adenocarcinoma: a multicenter cohort study. World J Surg Oncol, 2025, 23(1): 55.
29.	Zhang Y, Fu F, Chen H, et al. Sublobar resection versus lobectomy for stageⅠlung adenocarcinoma with EGFR mutations: a propensity score-matched analysis. Ann Thorac Surg, 2023, 116(5): 1240-1248.
30.	Del Palacio-Gonzalez A, Wonnacott A, Glover R, et al. An introduction to inverse probability of treatment weighting in observational research. Clin Kidney J, 2022, 15(1): 14-26.
31.	Yang S, Lorenzi E, Papadogeorgou G, et al. Propensity score weighting for causal subgroup analysis. Stat Med, 2022, 41(15): 2793-2810.

1. 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(4): 249-274.
2. 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(10335): 1607-1617.
3. Altorki NK, 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(6): 489-498.
4. Hattori A, Matsunaga T, Takamochi K, et al. Segmentectomy provides comparable survival to lobectomy for clinical stage ⅠA lung adenocarcinoma with ground-glass opacity. Eur J Cardiothorac Surg, 2021, 59(5): 1043-1050.
5. Cho J, Kim J, Kim K, et al. Long-term outcomes of segmentectomy versus lobectomy for stage I lung adenocarcinoma: a nationwide cohort study. J Thorac Cardiovasc Surg, 2022, 164(6): 1705-1716.
6. Zou J, Chen H, Fu F, et al. Sublobar resections for peripheral non-small cell lung cancer ≤2 cm: implications of randomized trials and remaining questions. Lung Cancer, 2024, 186: 107353.
7. Tsuboi M, Herbst RS, Winton T, et al. Overall survival with osimertinib in resected EGFR-mutated NSCLC. N Engl J Med, 2023, 389(2): 137-147.
8. Jiang Y, He X, Li W, et al. Adjuvant EGFR-TKI for resected EGFR-mutated non-small cell lung cancer: a systematic review and meta-analysis of randomized controlled trials. eClinicalMedicine, 2023, 64: 102205.
9. Furuya N, Yamada T, Morita S, et al. Adjuvant osimertinib for resected EGFR-mutated stage IB-ⅢA NSCLC: updated disease-free survival and safety. J Clin Oncol, 2023, 41(15_suppl): 8500.
10. Suzuki K, Watanabe S, Wakabayashi M, et al. A single-arm study of sublobar resection for ground-glass opacity dominant peripheral lung cancer (JCOG0804/WJOG4507L). J Thorac Cardiovasc Surg, 2022, 164(2): 289-301.
11. Wu YL, John T, Grohe C, et al. Osimertinib in resected EGFR-mutated non-small-cell lung cancer: CNS disease recurrence and outcomes. J Clin Oncol, 2022, 40(21): e200-e210.
12. Li N, Deng Y, Zhou X, et al. Driver mutation-positive stage I lung adenocarcinoma: clinicopathologic features and survival outcomes in a multicenter cohort. J Thorac Oncol, 2021, 16(11): 1893-1905.
13. Yamashita S, Tokuishi K, Moroga T, et al. Pleural invasion and lymphovascular invasion predict recurrence after complete resection of stage I lung adenocarcinoma. Ann Surg Oncol, 2022, 29(9): 5565-5574.
14. Kakugawa K, Murakawa T, Nakajima J, et al. Brief report: validation study of the IASLC histological grading system of invasive lung adenocarcinoma. J Thorac Oncol, 2021, 16(10): 1754-1759.
15. Yotsukura M, Asamura H, Motoi N, et al. Visceral pleural invasion and micropapillary/solid components are associated with recurrence in stage I lung adenocarcinoma. J Thorac Oncol, 2022, 17(7): 932-942.
16. Tsao MS, Nicholson AG, Maleszewski JJ, et al. IASLC/ATS/ERS classification and grading updates for lung adenocarcinoma: implications for prognosis and adjuvant therapy. J Thorac Oncol, 2021, 16(9): 1485-1486.
17. Kadota K, Kushida Y, Kagawa S, et al. Spread through air spaces (STAS) is an independent predictor of recurrence in stage I lung adenocarcinoma after limited resection: a systematic review and meta-analysis. Lung Cancer, 2021, 156: 1-9.
18. Feng T, Li J, He Y, et al. High-risk features associated with recurrence in stage I lung adenocarcinoma. J Thorac Cardiovasc Surg, 2024, 168(3): 781-789.
19. Haruki T, Aokage K, Miyoshi T, et al. Visceral pleural invasion and STAS predict recurrence after sublobar resection for early-stage lung adenocarcinoma. Eur J Cardiothorac Surg, 2022, 61(4): 799-807.
20. Brunelli A, Decaluwe H, Gonzalez M, et al. European Society of Thoracic Surgeons expert consensus recommendations on technical standards of segmentectomy for primary lung cancer. Eur J Cardiothorac Surg, 2023, 63(6): ezad224.
21. Liu Y, Matsouaka RA, Thomas L, et al. A tutorial for propensity score weighting methods under violations of the positivity assumption. Stat Med, 2025, 44(5): 1011-1035.
22. Zhou T, Tong G, Li F, et al. PSweight: An R package for propensity score weighting analysis. R J, 2022, 14(1): 282-300.
23. Li F, Li F, Thomas LE. Addressing extreme propensity scores via the overlap weights. Am J Epidemiol, 2021, 190(12): 2507-2515.
24. Yoshida K, Solomon DH, Kim SC, et al. Multinomial extension of propensity score trimming methods: a simulation study. Am J Epidemiol, 2021, 190(12): 2696-2705.
25. Ciolino JD, Martin RH, Zhao W, et al. Reporting and interpreting causal inference analyses using propensity scores in clinical research. JAMA Netw Open, 2021, 4(6): e2111696.
26. Wu YL, Tsuboi M, He J, et al. Osimertinib in resected EGFR-mutated non-small-cell lung cancer. N Engl J Med, 2020, 383(18): 1711-1723.
27. Liu Z, Wang Y, Chen X, et al. Adjuvant EGFR-TKI therapy for pathologic stageⅠEGFR-mutated lung adenocarcinoma: a real-world study. Clin Lung Cancer, 2025, 26(1): e1-e10.
28. Wang J, Li H, Zhang Y, et al. Adjuvant EGFR-TKI improves disease-free survival in high-risk stage IA lung adenocarcinoma: a multicenter cohort study. World J Surg Oncol, 2025, 23(1): 55.
29. Zhang Y, Fu F, Chen H, et al. Sublobar resection versus lobectomy for stageⅠlung adenocarcinoma with EGFR mutations: a propensity score-matched analysis. Ann Thorac Surg, 2023, 116(5): 1240-1248.
30. Del Palacio-Gonzalez A, Wonnacott A, Glover R, et al. An introduction to inverse probability of treatment weighting in observational research. Clin Kidney J, 2022, 15(1): 14-26.
31. Yang S, Lorenzi E, Papadogeorgou G, et al. Propensity score weighting for causal subgroup analysis. Stat Med, 2022, 41(15): 2793-2810.

Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

Latest ArticlesRole of postoperative adjuvant targeted therapy in survival outcomes after sublobar resection in patients with EGFR-mutated stageⅠ (T≤3 cm) invasive lung adenocarcinoma: A retrospective cohort study

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