Clinical effect of tumor spread through air spaces on prognosis in non-small cell lung cancer: A systematic review and meta-analysis_Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

Authors：

LIU Cong ¹ , JIANG Yuanrui ² ,  MAO Naiquan ³ , WANG Shoufeng ³ , SU Liufu ³

1. Graduate School of Guangxi Medical University, Nanning, 530021, P. R. China;
2. Graduate School of Guangxi University of Chinese Medicine, Nanning, 530022, P. R. China;
3. Department of Thoracic Surgery, Guangxi Tumor Hospital, Nanning, 530021, P. R. China;

Corresponding author：

MAO Naiquan, Email: maonaiquan@126.com

Keywords：

Spread through air spaces; non-small cell lung cancer; surgical treatment; prognosis; systematic review/meta-analysis

DOI：

10.7507/1007-4848.202011025

Video：

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Objective To explore the potential role of tumor spread through air spaces (STAS) as a prognostic indicator of non-small cell lung cancer (NSCLC) through meta-analysis.Methods PubMed, EMbase and Web of Science, from inception to February 2022 were searched by computer about the research of the 5-year overall survival (OS) and recurrence free survival (RFS) of NSCLC patients with or without STAS. The Newcastle-Ottawa scale (NOS) was used to evaluate the quality of each study.Results Totally 13 published articles were included with 4 647 patients, and1 424 (30.6%) patients had STAS. The NOS score of all studies≥6 points. The meta-analysis showed that compared with the NSCLC patients without STAS, those with STAS had a worse prognosis of 5-year RFS, and the combined HR was 1.89 (95%CI 1.61-2.23); they had a shorter 5-year OS, and the combined HR was 2.25 (95%CI 1.79-2.84). There was no statistical heterogeneity among studies.Conclusion The presence of STAS may be a poor prognostic factor for patients with NSCLC, and enough attention should be paid. The STAS should be recorded in the pathological report to guide the comprehensive treatment and evaluate the prognosis of patients.

Citation： LIU Cong, JIANG Yuanrui, MAO Naiquan, WANG Shoufeng, SU Liufu. Clinical effect of tumor spread through air spaces on prognosis in non-small cell lung cancer: A systematic review and meta-analysis. Chinese Journal of Clinical Thoracic and Cardiovascular Surgery, 2022, 29(5): 642-650. doi: 10.7507/1007-4848.202011025 Copy

1.	Siegel RL, Miller KD, Jemal A. Cancer statistics, 2020. CA Cancer J Clin, 2020, 70(1): 7-30.
2.	Kadota K, Nitadori JI, Sima CS, et al. Tumor spread through air spaces is an important pattern of invasion and impacts the frequency and location of recurrences after limited resection for small stage Ⅰ lung adenocarcinomas. J Thorac Oncol, 2015, 10(5): 806-814.
3.	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(9): 1243-1260.
4.	Shiono S, Yanagawa N. Spread through air spaces is a predictive factor of recurrence and a prognostic factor in stage Ⅰ lung adenocarcinoma. Interact Cardiovasc Thorac Surg, 2016, 23(4): 567-572.
5.	Warth A, Muley T, Kossakowski CA, et al. Prognostic impact of intra-alveolar tumor spread in pulmonary adenocarcinoma. Am J Surg Pathol, 2015, 39(6): 793-801.
6.	Uruga H, Fujii T, Fujimori S, et al. Semiquantitative assessment of tumor spread through air spaces (STAS) in early-stage lung adenocarcinomas. J Thorac Oncol, 2017, 12(7): 1046-1051.
7.	Travis WD, Brambilla E, Noguchi M, et al. International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society international multidisciplinary classification of lung adenocarcinoma. J Thorac Oncol, 2011, 6(2): 244-285.
8.	Lu S, Tan KS, Kadota K, et al. Spread through air spaces (STAS) is an independent predictor of recurrence and lung cancer-specific death in squamous cell carcinoma. J Thorac Oncol, 2017, 12(2): 223-234.
9.	Yanagawa N, Shiono S, Endo M, et al. Tumor spread through air spaces is a useful predictor of recurrence and prognosis in stage Ⅰ lung squamous cell carcinoma, but not in stage Ⅱ and Ⅲ. Lung Cancer, 2018, 120: 14-21.
10.	Kadota K, Kushida Y, Katsuki N, et al. Tumor spread through air spaces is an independent predictor of recurrence-free survival in patients with resected lung squamous Cell Carcinoma. Am J Surg Pathol, 2017, 41(8): 1077-1086.
11.	Dai C, Xie H, Su H, et al. Tumor spread through air spaces affects the recurrence and overall survival in patients with lung adenocarcinoma > 2 to 3 cm. J Thorac Oncol, 2017, 12(7): 1052-1060.
12.	Egger M, Davey Smith G, Schneider M, et al. Bias in meta-analysis detected by a simple, graphical test. BMJ, 1997, 315(7109): 629-634.
13.	Begg CB, Mazumdar M. Operating characteristics of a rank correlation test for publication bias. Biometrics, 1994, 50(4): 1088-1101.
14.	Ren Y, Xie H, Dai C, et al. Prognostic impact of tumor spread through air spaces in sublobar resection for 1a lung adenocarcinoma patients. Ann Surg Oncol, 2019, 26(6): 1901-1908.
15.	Shiono S, Endo M, Suzuki K, et al. Spread through air spaces is a prognostic factor in sublobar resection of non-small cell lung cancer. Ann Thorac Surg, 2018, 106(2): 354-360.
16.	Shiono S, Endo M, Suzuki K, et al. Spread through air spaces in lung cancer patients is a risk factor for pulmonary metastasis after surgery. J Thorac Dis, 2019, 11(1): 177-187.
17.	Terada Y, Takahashi T, Morita S, et al. Spread through air spaces is an independent predictor of recurrence in stage Ⅲ (N2) lung adenocarcinoma. Interact Cardiovasc Thorac Surg, 2019, 29(3): 442-448.
18.	Toyokawa G, Yamada Y, Tagawa T, et al. Significance of spread through air spaces in resected pathological stage Ⅰ lung adenocarcinoma. Ann Thorac Surg, 2018, 105(6): 1655-1663.
19.	Kang YK, Song YS, Cho S, et al. Prognostic stratification model for patients with stage Ⅰ non-small cell lung cancer adenocarcinoma treated with surgical resection without adjuvant therapies using metabolic features measured on F-18 FDG PET and postoperative pathologic factors. Lung Cancer, 2018, 119: 1-6.
20.	Liu Y, Chen D, Qiu X, et al. Relationship between MTA1 and spread through air space and their joint influence on prognosis of patients with stageⅠ-Ⅲ lung adenocarcinoma. Lung Cancer, 2018, 124: 211-218.
21.	Kadota K, Kushida Y, Kagawa S, et al. Limited resection is associated with a higher risk of locoregional recurrence than lobectomy in stageⅠ lung adenocarcinoma with tumor spread through air spaces. Am J Surg Pathol, 2019, 43(8): 1033-1041.
22.	Eguchi T, Kameda K, Lu S, et al. Lobectomy is associated with better outcomes than sublobar resection in spread through air spaces (STAS)-positive T1 lung adenocarcinoma: A propensity score-matched analysis. J Thorac Oncol, 2019, 14(1): 87-98.
23.	Travis WD, Asamura H, Bankier AA, et al. The IASLC lung cancer staging project: Proposals for coding t categories for subsolid nodules and assessment of tumor size in part-solid tumors in the forthcoming eighth edition of the TNM classification of lung cancer. J Thorac Oncol, 2016, 11(8): 1204-1223.
24.	Amin MB, Tamboli P, Merchant SH, et al. Micropapillary component in lung adenocarcinoma: A distinctive histologic feature with possible prognostic significance. Am J Surg Pathol, 2002, 26(3): 358-364.
25.	Onozato ML, Kovach AE, Yeap BY, et al. Tumor islands in resected early-stage lung adenocarcinomas are associated with unique clinicopathologic and molecular characteristics and worse prognosis. Am J Surg Pathol, 2013, 37(2): 287-294.
26.	Vaghjiani RG, Takahashi Y, Eguchi T, et al. Tumor spread through air spaces is a predictor of occult lymph node metastasis in clinical stage ⅠA lung adenocarcinoma. J Thorac Oncol, 2020, 15(5): 792-802.
27.	Blaauwgeers H, Flieder D, Warth A, et al. A prospective study of loose tissue fragments in non-small cell lung cancer resection specimens: An alternative view to "spread through air spaces". Am J Surg Pathol, 2017, 41(9): 1226-1230.
28.	Qi L, Xue K, Cai Y, et al. Predictors of CT morphologic features to identify spread through air spaces preoperatively in small-sized lung adenocarcinoma. Front Oncol, 2021, 10: 548430.
29.	Suzuki K. JCOG0201 defined "radiological early peripheral lung adenocarcinoma". J Thorac Oncol, 2011, 6(8): 1452-1453.
30.	Suzuki K, Watanabe SI, Wakabayashi M, et al. A single-arm study of sublobar resection for ground-glass opacity dominant peripheral lung cancer. J Thorac Cardiovasc Surg, 2022, 163(1): 289-301.

1. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2020. CA Cancer J Clin, 2020, 70(1): 7-30.
2. Kadota K, Nitadori JI, Sima CS, et al. Tumor spread through air spaces is an important pattern of invasion and impacts the frequency and location of recurrences after limited resection for small stage Ⅰ lung adenocarcinomas. J Thorac Oncol, 2015, 10(5): 806-814.
3. 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(9): 1243-1260.
4. Shiono S, Yanagawa N. Spread through air spaces is a predictive factor of recurrence and a prognostic factor in stage Ⅰ lung adenocarcinoma. Interact Cardiovasc Thorac Surg, 2016, 23(4): 567-572.
5. Warth A, Muley T, Kossakowski CA, et al. Prognostic impact of intra-alveolar tumor spread in pulmonary adenocarcinoma. Am J Surg Pathol, 2015, 39(6): 793-801.
6. Uruga H, Fujii T, Fujimori S, et al. Semiquantitative assessment of tumor spread through air spaces (STAS) in early-stage lung adenocarcinomas. J Thorac Oncol, 2017, 12(7): 1046-1051.
7. Travis WD, Brambilla E, Noguchi M, et al. International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society international multidisciplinary classification of lung adenocarcinoma. J Thorac Oncol, 2011, 6(2): 244-285.
8. Lu S, Tan KS, Kadota K, et al. Spread through air spaces (STAS) is an independent predictor of recurrence and lung cancer-specific death in squamous cell carcinoma. J Thorac Oncol, 2017, 12(2): 223-234.
9. Yanagawa N, Shiono S, Endo M, et al. Tumor spread through air spaces is a useful predictor of recurrence and prognosis in stage Ⅰ lung squamous cell carcinoma, but not in stage Ⅱ and Ⅲ. Lung Cancer, 2018, 120: 14-21.
10. Kadota K, Kushida Y, Katsuki N, et al. Tumor spread through air spaces is an independent predictor of recurrence-free survival in patients with resected lung squamous Cell Carcinoma. Am J Surg Pathol, 2017, 41(8): 1077-1086.
11. Dai C, Xie H, Su H, et al. Tumor spread through air spaces affects the recurrence and overall survival in patients with lung adenocarcinoma > 2 to 3 cm. J Thorac Oncol, 2017, 12(7): 1052-1060.
12. Egger M, Davey Smith G, Schneider M, et al. Bias in meta-analysis detected by a simple, graphical test. BMJ, 1997, 315(7109): 629-634.
13. Begg CB, Mazumdar M. Operating characteristics of a rank correlation test for publication bias. Biometrics, 1994, 50(4): 1088-1101.
14. Ren Y, Xie H, Dai C, et al. Prognostic impact of tumor spread through air spaces in sublobar resection for 1a lung adenocarcinoma patients. Ann Surg Oncol, 2019, 26(6): 1901-1908.
15. Shiono S, Endo M, Suzuki K, et al. Spread through air spaces is a prognostic factor in sublobar resection of non-small cell lung cancer. Ann Thorac Surg, 2018, 106(2): 354-360.
16. Shiono S, Endo M, Suzuki K, et al. Spread through air spaces in lung cancer patients is a risk factor for pulmonary metastasis after surgery. J Thorac Dis, 2019, 11(1): 177-187.
17. Terada Y, Takahashi T, Morita S, et al. Spread through air spaces is an independent predictor of recurrence in stage Ⅲ (N2) lung adenocarcinoma. Interact Cardiovasc Thorac Surg, 2019, 29(3): 442-448.
18. Toyokawa G, Yamada Y, Tagawa T, et al. Significance of spread through air spaces in resected pathological stage Ⅰ lung adenocarcinoma. Ann Thorac Surg, 2018, 105(6): 1655-1663.
19. Kang YK, Song YS, Cho S, et al. Prognostic stratification model for patients with stage Ⅰ non-small cell lung cancer adenocarcinoma treated with surgical resection without adjuvant therapies using metabolic features measured on F-18 FDG PET and postoperative pathologic factors. Lung Cancer, 2018, 119: 1-6.
20. Liu Y, Chen D, Qiu X, et al. Relationship between MTA1 and spread through air space and their joint influence on prognosis of patients with stageⅠ-Ⅲ lung adenocarcinoma. Lung Cancer, 2018, 124: 211-218.
21. Kadota K, Kushida Y, Kagawa S, et al. Limited resection is associated with a higher risk of locoregional recurrence than lobectomy in stageⅠ lung adenocarcinoma with tumor spread through air spaces. Am J Surg Pathol, 2019, 43(8): 1033-1041.
22. Eguchi T, Kameda K, Lu S, et al. Lobectomy is associated with better outcomes than sublobar resection in spread through air spaces (STAS)-positive T1 lung adenocarcinoma: A propensity score-matched analysis. J Thorac Oncol, 2019, 14(1): 87-98.
23. Travis WD, Asamura H, Bankier AA, et al. The IASLC lung cancer staging project: Proposals for coding t categories for subsolid nodules and assessment of tumor size in part-solid tumors in the forthcoming eighth edition of the TNM classification of lung cancer. J Thorac Oncol, 2016, 11(8): 1204-1223.
24. Amin MB, Tamboli P, Merchant SH, et al. Micropapillary component in lung adenocarcinoma: A distinctive histologic feature with possible prognostic significance. Am J Surg Pathol, 2002, 26(3): 358-364.
25. Onozato ML, Kovach AE, Yeap BY, et al. Tumor islands in resected early-stage lung adenocarcinomas are associated with unique clinicopathologic and molecular characteristics and worse prognosis. Am J Surg Pathol, 2013, 37(2): 287-294.
26. Vaghjiani RG, Takahashi Y, Eguchi T, et al. Tumor spread through air spaces is a predictor of occult lymph node metastasis in clinical stage ⅠA lung adenocarcinoma. J Thorac Oncol, 2020, 15(5): 792-802.
27. Blaauwgeers H, Flieder D, Warth A, et al. A prospective study of loose tissue fragments in non-small cell lung cancer resection specimens: An alternative view to "spread through air spaces". Am J Surg Pathol, 2017, 41(9): 1226-1230.
28. Qi L, Xue K, Cai Y, et al. Predictors of CT morphologic features to identify spread through air spaces preoperatively in small-sized lung adenocarcinoma. Front Oncol, 2021, 10: 548430.
29. Suzuki K. JCOG0201 defined "radiological early peripheral lung adenocarcinoma". J Thorac Oncol, 2011, 6(8): 1452-1453.
30. Suzuki K, Watanabe SI, Wakabayashi M, et al. A single-arm study of sublobar resection for ground-glass opacity dominant peripheral lung cancer. J Thorac Cardiovasc Surg, 2022, 163(1): 289-301.

Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

Clinical effect of tumor spread through air spaces on prognosis in non-small cell lung cancer: A systematic review and meta-analysis

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