Spread Through Air Spaces (STAS) in Pulmonary Adenocarcinoma: Prognostic Meaning and Surgical Implications
Main Article Content
Spread Through Air Spaces (STAS) is a pattern of cancer cell invasion found in pulmonary adenocarcinoma and has been identified as a significant independent prognostic factor. The presence of STAS is closely related to an increased risk of local recurrence and a decrease in survival rates, especially in patients undergoing limited resection. This study aims to review the literature related to the prognostic significance and surgical implications of STAS, as well as to evaluate preoperative and intraoperative diagnostic approaches such as CT scans, PET/CT, frozen section, and radiomics. The findings suggest that although the definitive diagnosis of STAS can only be established postoperatively, the development of preoperative predictive technologies is critical in supporting more informed clinical decision-making. It is hoped that STAS can be included in international clinical guidelines to assist in the determination of individualized therapy strategies for lung cancer patients.
Keywords:
STAS, pulmonary adenocarcinoma, surgical prognosis
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13. Solis LM, Behrens C, Raso MG, Lin HY, Kadara H, Yuan P, et al. Histologic Patterns and Molecular Characteristics of Lung Adenocarcinoma Associated With Clinical Outcome. Cancer. 2012 June 1; 118(11):2889–99.
14. Lu L, Xu H. An Update on the Classification of Lung and Pleural Tumors. Journal of Clinical and Translational Pathology. 2023 June 25; 3(2):106–13.
15. Chen HZ, Bertino EM, He K. Tumor spread through air space (STAS) is an important predictor of clinical outcome in stage IA lung adenocarcinoma. Journal of Thoracic Disease [Internet]. 2017 Aug [cited 2025 Jun 28]; 9(8). Available from: https://jtd.amegroups.org/article/view/15009
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19. Nicotra S, Melan L, Pezzuto F, Bonis A, Silvestrin S, Verzeletti V, et al. Significance of Spread Through Air Spaces and Vascular Invasion in Early-stage Adenocarcinoma Survival: A Comprehensive Clinicopathologic Study of 427 Patients for Precision Management. The American Journal of Surgical Pathology. May 2024; 48(5):605.
20. Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. May 2021; 71(3):209–49.
21. Wang Y, Lyu D, Fan L, Liu S. Advances in the prediction of spread through air spaces with imaging in lung cancer: a narrative review. Transl Cancer Res. 2023 Mar 31; 12(3):624–30.
22. T E, K K, S L, Mj B, Ks T, J M, 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. Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer [Internet]. 2019 Jan [cited 2025 Jun 29]; 14(1). Available from: https://pubmed.ncbi.nlm.nih.gov/30244070/?utm_source=chatgpt.com
23. Cao L, Jia M, Sun PL, Gao H. Histopathologic features from preoperative biopsies to predict spread through air spaces in early-stage lung adenocarcinoma: a retrospective study. BMC Cancer. 2021 Aug 11; 21(1):913.
24. Zhou F, Villalba JA, Sayo TMS, Narula N, Pass H, Mino-Kenudson M, et al. Assessment of the feasibility of frozen sections for the detection of spread through air spaces (STAS) in pulmonary adenocarcinoma. Mod. Feb. 2022; 35(2):210–7.
25. Xu F, Liu Z, Yan J, Yan L, Qiu Z, Ge Y, et al. Feasibility of intraoperative assessment of STAS in pathologic stage 1 lung adenocarcinomas in Chinese patients. Eur J Surg Oncol. 2024 Oct 8;108747.
26. Medina MA, Onken AM, de Margerie-Mellon C, Heidinger BH, Chen Y, Bankier AA, et al. Preoperative bronchial cytology for the assessment of tumor spread through air spaces in lung adenocarcinoma resection specimens. Cancer Cytopathology. 2020; 128(4):278–86.
27. Travis W, Gaber R, Lu S, Eguchi T, Rekhtman N, Adusumilli P. MS10.04 Therapeutic implications of spread through air spaces (STAS). Journal of Thoracic Oncology. 2018 Oct 1; 13(10):S265–6.
28. Kim SK, Kim TJ, Chung MJ, Kim TS, Lee KS, Zo JI, et al. Lung Adenocarcinoma: CT Features Associated with Spread through Air Spaces. Radiology. 2018 Dec; 289(3):831–40.
29. Volpi S, Ali JM, Tasker A, Peryt A, Aresu G, Coonar AS. The role of positron emission tomography in the diagnosis, staging and response assessment of non-small cell lung cancer. Ann Transl Med. 2018 Mar; 6(5):95.
30. Herba M, Boczek S, Smy?a-Gruca W, Kost K, Czy?ewski D, Rydel M. Spread Through Air Spaces (STAS) as a Predictive and Prognostic Factor in Patients with Non-Small Cell Lung Cancer—Systematic Review. Cancers. 2025 Jan; 17(10):1696.
31. Travis WD, Eisele M, Nishimura KK, Aly RG, Bertoglio P, Chou TY, et al. The International Association for the Study of Lung Cancer (IASLC) Staging Project for Lung Cancer: Recommendation to Introduce Spread Through Air Spaces as a Histologic Descriptor in the Ninth Edition of the TNM Classification of Lung Cancer. Analysis of 4061 Pathologic Stage I NSCLC. Journal of Thoracic Oncology. 2024 Jul 1; 19(7):1028–51.
2. Kadota K, Kushida Y, Kagawa S, Ishikawa R, Ibuki E, Inoue K, et al. Limited Resection Is Associated With a Higher Risk of Locoregional Recurrence than Lobectomy in Stage I Lung Adenocarcinoma With Tumor Spread Through Air Spaces. Am J Surg Pathol. Aug. 2019; 43(8):1033–41.
3. Giraud P, Antoine M, Larrouy A, Milleron B, Callard P, De Rycke Y, et al. Evaluation of microscopic tumor extension in non-small-cell lung cancer for three-dimensional conformal radiotherapy planning. Int J Radiat Oncol Biol Phys. 2000 Nov 1; 48(4):1015–24.
4. Travis WD, Brambilla E, Nicholson AG, Yatabe Y, Austin JHM, Beasley MB, 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 Sep; 10(9):1243–60.
5. Mino-Kenudson M. Significance of tumor spread through air spaces (STAS) in lung cancer from the pathologist perspective. Transl Lung Cancer Res. 2020 June; 9(3):847–59.
6. Gross DJ, Hsieh MS, Li Y, Dux J, Rekhtman N, Jones DR, et al. Spread Through Air Spaces (STAS) in Non-Small Cell Lung Carcinoma: Evidence Supporting of an In Vivo Phenomenon. Am J Surg Pathol. 2021 Nov 1; 45(11):1509–15.
7. Takahashi Y, Kuroda H, Oya Y, Matsutani N, Matsushita H, Kawamura M. Challenges for real-time intraoperative diagnosis of high risk histology in lung adenocarcinoma: A necessity for sublobar resection. Thoracic Cancer. Aug. 2019; 10(8):1663–8.
8. Masai K, Sakurai H, Sukeda A, Suzuki S, Asakura K, Nakagawa K, et al. Prognostic Impact of Margin Distance and Tumor Spread Through Air Spaces in Limited Resection for Primary Lung Cancer. J Thorac Oncol. 2017 Dec; 12(12):1788–97.
9. Kumar A, Kumar A. Non-small-cell lung cancer-associated gene mutations and inhibitors. Advances in Cancer Biology - Metastasis. 2022 Dec 1;6:100076.
10. Siddiqui F, Vaqar S, Siddiqui AH. Lung Cancer. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 [cited 2025 Jun 28]. Available from: http://www.ncbi.nlm.nih.gov/books/NBK482357/
11. Lindeman NI, Cagle PT, Aisner DL, Arcila ME, Beasley MB, Bernicker EH, et al. Updated Molecular Testing Guideline for the Selection of Lung Cancer Patients for Treatment With Targeted Tyrosine Kinase Inhibitors: Guideline From the College of American Pathologists, the International Association for the Study of Lung Cancer, and the Association for Molecular Pathology. J Mol Diagn. 2018 Mar; 20(2):129–59.
12. Nicholson AG, Tsao MS, Beasley MB, Borczuk AC, Brambilla E, Cooper WA, et al. The 2021 WHO Classification of Lung Tumors: Impact of Advances Since 2015. Journal of Thoracic Oncology. 2022 Mar 1; 17(3):362–87.
13. Solis LM, Behrens C, Raso MG, Lin HY, Kadara H, Yuan P, et al. Histologic Patterns and Molecular Characteristics of Lung Adenocarcinoma Associated With Clinical Outcome. Cancer. 2012 June 1; 118(11):2889–99.
14. Lu L, Xu H. An Update on the Classification of Lung and Pleural Tumors. Journal of Clinical and Translational Pathology. 2023 June 25; 3(2):106–13.
15. Chen HZ, Bertino EM, He K. Tumor spread through air space (STAS) is an important predictor of clinical outcome in stage IA lung adenocarcinoma. Journal of Thoracic Disease [Internet]. 2017 Aug [cited 2025 Jun 28]; 9(8). Available from: https://jtd.amegroups.org/article/view/15009
16. (PDF) Pathology Section: An update on WHO Classification of Thoracic Tumours 2021-Newly Described Entities and Terminologies. ResearchGate [Internet]. [cited 2025 Jun 28]; Available from: https://www.researchgate.net/publication/371753375_Pathology_Section_An_Update_on_WHO_Classification_of_Thoracic_Tumours_2021-Newly_Described_Entities_and_Terminologies
17. Onozato ML, Kovach AE, Yeap BY, Morales-Oyarvide V, Klepeis VE, Tammireddy S, 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. Feb. 2013; 37(2):287–94.
18. Garlin-Politis M, Saqi A, Mino-Kenudson M. Spread Through Air Spaces: Interresponder Agreement and Comparison Between Pulmonary and General Pathologists. Mod. 2024 Nov; 37(11):100596.
19. Nicotra S, Melan L, Pezzuto F, Bonis A, Silvestrin S, Verzeletti V, et al. Significance of Spread Through Air Spaces and Vascular Invasion in Early-stage Adenocarcinoma Survival: A Comprehensive Clinicopathologic Study of 427 Patients for Precision Management. The American Journal of Surgical Pathology. May 2024; 48(5):605.
20. Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. May 2021; 71(3):209–49.
21. Wang Y, Lyu D, Fan L, Liu S. Advances in the prediction of spread through air spaces with imaging in lung cancer: a narrative review. Transl Cancer Res. 2023 Mar 31; 12(3):624–30.
22. T E, K K, S L, Mj B, Ks T, J M, 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. Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer [Internet]. 2019 Jan [cited 2025 Jun 29]; 14(1). Available from: https://pubmed.ncbi.nlm.nih.gov/30244070/?utm_source=chatgpt.com
23. Cao L, Jia M, Sun PL, Gao H. Histopathologic features from preoperative biopsies to predict spread through air spaces in early-stage lung adenocarcinoma: a retrospective study. BMC Cancer. 2021 Aug 11; 21(1):913.
24. Zhou F, Villalba JA, Sayo TMS, Narula N, Pass H, Mino-Kenudson M, et al. Assessment of the feasibility of frozen sections for the detection of spread through air spaces (STAS) in pulmonary adenocarcinoma. Mod. Feb. 2022; 35(2):210–7.
25. Xu F, Liu Z, Yan J, Yan L, Qiu Z, Ge Y, et al. Feasibility of intraoperative assessment of STAS in pathologic stage 1 lung adenocarcinomas in Chinese patients. Eur J Surg Oncol. 2024 Oct 8;108747.
26. Medina MA, Onken AM, de Margerie-Mellon C, Heidinger BH, Chen Y, Bankier AA, et al. Preoperative bronchial cytology for the assessment of tumor spread through air spaces in lung adenocarcinoma resection specimens. Cancer Cytopathology. 2020; 128(4):278–86.
27. Travis W, Gaber R, Lu S, Eguchi T, Rekhtman N, Adusumilli P. MS10.04 Therapeutic implications of spread through air spaces (STAS). Journal of Thoracic Oncology. 2018 Oct 1; 13(10):S265–6.
28. Kim SK, Kim TJ, Chung MJ, Kim TS, Lee KS, Zo JI, et al. Lung Adenocarcinoma: CT Features Associated with Spread through Air Spaces. Radiology. 2018 Dec; 289(3):831–40.
29. Volpi S, Ali JM, Tasker A, Peryt A, Aresu G, Coonar AS. The role of positron emission tomography in the diagnosis, staging and response assessment of non-small cell lung cancer. Ann Transl Med. 2018 Mar; 6(5):95.
30. Herba M, Boczek S, Smy?a-Gruca W, Kost K, Czy?ewski D, Rydel M. Spread Through Air Spaces (STAS) as a Predictive and Prognostic Factor in Patients with Non-Small Cell Lung Cancer—Systematic Review. Cancers. 2025 Jan; 17(10):1696.
31. Travis WD, Eisele M, Nishimura KK, Aly RG, Bertoglio P, Chou TY, et al. The International Association for the Study of Lung Cancer (IASLC) Staging Project for Lung Cancer: Recommendation to Introduce Spread Through Air Spaces as a Histologic Descriptor in the Ninth Edition of the TNM Classification of Lung Cancer. Analysis of 4061 Pathologic Stage I NSCLC. Journal of Thoracic Oncology. 2024 Jul 1; 19(7):1028–51.
