Current Status and Perspectives of Spread Through Air Spaces in Lung Cancer

Overview

Journal Thorac Cancer

Specialties Oncology
Pulmonary Medicine

Date 2021 May 5

PMID 33951312

Citations 5

Authors

Toshihiro Ikeda

Kyuichi Kadota

Tetsuhiko Go

Reiji Haba

Hiroyasu Yokomise

Affiliations

Soon will be listed here.

Abstract

According to the World Health Organization classification of 2015, spread through air spaces (STAS) is a newly recognized pattern of invasion in lung adenocarcinoma. Many researchers have reported that STAS is recognized in all histological subtypes, and there is a strong association between STAS and prognosis in lung cancer. However, there are several technical issues associated with STAS, such as distinction between the actual in vivo phenomenon and an artifact, difficulty in assessing STAS in frozen specimens, and establishing the relationship between morphological and molecular properties of STAS. This review focuses on the current state of knowledge and the outlook of the STAS phenomenon from the perspective of surgeons, pathologists, and radiologists.

Citing Articles

Prediction of STAS in lung adenocarcinoma with nodules ≤ 2 cm using machine learning: a multicenter retrospective study.

Zhang Z, Zhao Y, Ma Y, Chen C, Li Z, Wang Y BMC Cancer. 2025; 25(1):417.

PMID: 40055661 PMC: 11887330. DOI: 10.1186/s12885-025-13783-z.

Does dual-layer spectral detector CT provide added value in predicting spread through air spaces in lung adenocarcinoma? A preliminary study.

Liu B, Ma H, Huang J, Luo Y, Zhang W, Deng W Eur Radiol. 2023; 34(6):4176-4186.

PMID: 37973632 DOI: 10.1007/s00330-023-10440-6.

Comprehensive molecular characterizations of stage I-III lung adenocarcinoma with tumor spread through air spaces.

Ye R, Yu Y, Zhao R, Han Y, Lu S Front Genet. 2023; 14:1101443.

PMID: 36816028 PMC: 9932204. DOI: 10.3389/fgene.2023.1101443.

To explore the prognostic value of spread through air spaces and develop a nomogram combined with spread through air spaces in lung squamous cell carcinoma.

Yu H, Lin C, Chen X, Wang Z, Shen W J Thorac Dis. 2022; 14(9):3531-3543.

PMID: 36245609 PMC: 9562524. DOI: 10.21037/jtd-22-1065.

Study on the Relationship between Lung Cancer Stromal Cells and Air Cavity Diffusion Based on an Image Acquisition System.

Bai S, Wang Z, Sun Z, Liu Z Contrast Media Mol Imaging. 2022; 2022:2492124.

PMID: 35909590 PMC: 9303510. DOI: 10.1155/2022/2492124.

References

Blaauwgeers H, Flieder D, Warth A, Harms A, Monkhorst K, Witte B . 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. DOI: 10.1097/PAS.0000000000000889. View

Aly R, Rekhtman N, Li X, Takahashi Y, Eguchi T, Tan K . Spread Through Air Spaces (STAS) Is Prognostic in Atypical Carcinoid, Large Cell Neuroendocrine Carcinoma, and Small Cell Carcinoma of the Lung. J Thorac Oncol. 2019; 14(9):1583-1593. PMC: 8160527. DOI: 10.1016/j.jtho.2019.05.009. View

Onozato M, Kovach A, Yeap B, Morales-Oyarvide V, Klepeis V, Tammireddy S . Tumor islands in resected early-stage lung adenocarcinomas are associated with unique clinicopathologic and molecular characteristics and worse prognosis. Am J Surg Pathol. 2012; 37(2):287-94. PMC: 3545070. DOI: 10.1097/PAS.0b013e31826885fb. View

Chen D, Mao Y, Wen J, She Y, Zhu E, Zhu F . Tumor Spread Through Air Spaces in Non-Small Cell Lung Cancer: A Systematic Review and Meta-Analysis. Ann Thorac Surg. 2019; 108(3):945-954. DOI: 10.1016/j.athoracsur.2019.02.045. View

Kim S, Kim T, Chung M, Kim T, Lee K, Zo J . Lung Adenocarcinoma: CT Features Associated with Spread through Air Spaces. Radiology. 2018; 289(3):831-840. DOI: 10.1148/radiol.2018180431. View

Yanagawa N, Shiono S, Endo M, Ogata S . 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. DOI: 10.1016/j.lungcan.2018.03.018. View

Lu S, Tan K, Kadota K, Eguchi T, Bains S, Rekhtman N . Spread through Air Spaces (STAS) Is an Independent Predictor of Recurrence and Lung Cancer-Specific Death in Squamous Cell Carcinoma. J Thorac Oncol. 2016; 12(2):223-234. PMC: 5639476. DOI: 10.1016/j.jtho.2016.09.129. View

Torre L, Bray F, Siegel R, Ferlay J, Lortet-Tieulent J, Jemal A . Global cancer statistics, 2012. CA Cancer J Clin. 2015; 65(2):87-108. DOI: 10.3322/caac.21262. View

Kadota K, Kushida Y, Katsuki N, Ishikawa R, Ibuki E, Motoyama M . 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. DOI: 10.1097/PAS.0000000000000872. View

10.

Yokoyama S, Murakami T, Tao H, Onoda H, Hara A, Miyazaki R . Tumor Spread Through Air Spaces Identifies a Distinct Subgroup With Poor Prognosis in Surgically Resected Lung Pleomorphic Carcinoma. Chest. 2018; 154(4):838-847. DOI: 10.1016/j.chest.2018.06.007. View

11.

Ikeda T, Kadota K, Go T, Haba R, Yokomise H . Current status and perspectives of spread through air spaces in lung cancer. Thorac Cancer. 2021; 12(11):1639-1646. PMC: 8169306. DOI: 10.1111/1759-7714.13918. View

12.

Lee J, Kim E, Kim M, Shim H . Genetic and clinicopathologic characteristics of lung adenocarcinoma with tumor spread through air spaces. Lung Cancer. 2018; 123:121-126. DOI: 10.1016/j.lungcan.2018.07.020. View

13.

Eguchi T, Kameda K, Lu S, Bott M, Tan K, Montecalvo J . 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. 2018; 14(1):87-98. PMC: 6309668. DOI: 10.1016/j.jtho.2018.09.005. View

14.

Kadota K, Kushida Y, Kagawa S, Ishikawa R, Ibuki E, Inoue K . 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. 2019; 43(8):1033-1041. DOI: 10.1097/PAS.0000000000001285. View

15.

Jia M, Yu S, Yu J, Li Y, Gao H, Sun P . Comprehensive analysis of spread through air spaces in lung adenocarcinoma and squamous cell carcinoma using the 8th edition AJCC/UICC staging system. BMC Cancer. 2020; 20(1):705. PMC: 7391600. DOI: 10.1186/s12885-020-07200-w. View

16.

Onozato M, Klepeis V, Yagi Y, Mino-Kenudson M . A role of three-dimensional (3D) reconstruction in the classification of lung adenocarcinoma. Stud Health Technol Inform. 2012; 179:250-6. View

17.

Layfield L, Witt B, Metzger K, Anderson G . Extraneous tissue: a potential source for diagnostic error in surgical pathology. Am J Clin Pathol. 2011; 136(5):767-72. DOI: 10.1309/AJCP4FFSBPHAU8IU. View

18.

Uruga H, Fujii T, Fujimori S, Kohno T, Kishi K . Semiquantitative Assessment of Tumor Spread through Air Spaces (STAS) in Early-Stage Lung Adenocarcinomas. J Thorac Oncol. 2017; 12(7):1046-1051. DOI: 10.1016/j.jtho.2017.03.019. View

19.

Shiono S, Endo M, Suzuki K, Hayasaka K, Yanagawa N . 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. PMC: 6384349. DOI: 10.21037/jtd.2018.12.21. View

20.

Masai K, Sakurai H, Sukeda A, Suzuki S, Asakura K, Nakagawa K . Prognostic Impact of Margin Distance and Tumor Spread Through Air Spaces in Limited Resection for Primary Lung Cancer. J Thorac Oncol. 2017; 12(12):1788-1797. DOI: 10.1016/j.jtho.2017.08.015. View