Retrospective analysis of tumor spread through air spaces (STAS) in non-small cell lung cancer (NSCLC) cases

Abstract

Aim: Lung cancer is the leading cause of cancer-related mortality worldwide. Spread through air spaces (STAS) refers to tumor cells found within air spaces surrounding the main tumor mass and has been associated with poor prognosis. This study aimed to investigate the relationship between STAS positivity and clinical as well as pathological variables in operated non-small cell lung cancer (NSCLC) patients followed at our center. Material and Methods: Patients diagnosed with NSCLC who underwent surgery between January 2018 and May 2022 at our institution were retrospectively analyzed. The relationship between clinical and pathological variables and STAS was investigated. Survival analyses were performed using the Kaplan-Meier method. Results: A total of 85 cases were evaluated within the scope of the study. STAS positivity was observed in 64.7% (n=55) of patients. Low-grade tumors were less common in the STAS positive group (p = 0.006). Regarding lymph node involvement, the frequency of N2 disease was significantly higher in STAS positive patients compared to STAS negatives (p = 0.003). The presence of lymphovascular invasion (LVI) was also significantly higher in the STAS positive group (p = 0.011). Although disease-free survival (DFS) and overall survival (OS) were numerically higher in the STAS negative group, the difference was not statistically significant. Conclusion: In this study, a significant association was found between STAS positivity and N2 disease, grade, and LVI in patients diagnosed with NSCLC. Although survival times were found to be lower in STAS positive patients compared to the STAS negative group, this difference did not reach statistical significance.

Keywords

• Lung cancer
• spread through air spaces
• overall survival
• disease-free survival

Küçük hücreli dışı akciğer kanseri (KHDAK) olgularında hava yolları ile yayılımın (STAS) retrospektif analizi

Abstract

Amaç: Akciğer kanseri tüm dünyada kansere bağlı ölüme en sık yol açan kanser türüdür. Hava yolları ile yayılım (STAS) ana tümör kitlesi çevresindeki hava yolu boşluklarında görülen tümör hücrelerini ifade etmektedir ve kötü prognoz ile ilişkisi bilinmektedir. Çalışmamızda merkezimizde takipli opere küçük hücreli dışı akciğer kanserli hastalarda STAS pozitifliğinin klinik ve patolojik değişkenler ile olan ilişkisi araştırılmıştır. Gereç ve Yöntemler: Merkezimizde küçük hücreli dışı akciğer kanseri tanısı ile Ocak 2018 ile Mayıs 2022 tarihleri arasında opere olan hastalar retrospektif olarak değerlendirildi. Klinik ve patolojik değişkenler ile STAS ilişkisi araştırıldı. Sağkalım süreleri Kaplan-Meier yöntemi ile analiz edildi. Bulgular: Toplamda 85 olgu çalışma kapsamında değerlendirildi. STAS pozitiflik oranı %64.7 (n=55) idi. STAS pozitif grupta düşük tümör grade’ i daha az görüldü (p = 0,006). Lenf nodu tutulumuna göre ise STAS pozitif hastalarda N2 hastalık oranının belirgin olarak yüksek olduğu görüldü (p = 0,003). Lenfovasküler invazyon (LVİ) varlığı da STAS pozitif grupta anlamlı derecede yüksek saptandı (p = 0,011). Nümerik olarak STAS negatif grupta hastalıksız sağkalım (DFS) ve genel sağkalım (OS) süreleri yüksek olmasına rağmen bu durum istatistiksel anlamlılığa yansımadı. Sonuçlar: Çalışmamızda, opere küçük hücreli dışı akciğer kanseri tanılı hastalarda STAS pozitifliği ile N2 hastalık, grade ve LVİ arasında anlamlı ilişkili saptanmıştır. STAS pozitif hastalarda sağkalım süreleri STAS negatif gruba göre daha düşük saptanmasına rağmen bu durumun istatistiksel anlamlılığa ulaşmadığı görülmüştür.

Keywords

• Akciğer kanseri
• hava yolları ile yayılım
• genel sağkalım
• hastalıksız sağkalım

References

1. Bray F, Laversanne M, Sung H, Ferlay J, Siegel RL, Soerjomataram I, et al. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 2024;74:229-263.
2. Wang S, Xu J, Wang R, Qian F, Yang W, Qiao R, et al. Adjuvant chemotherapy may improve prognosis after resection of stage I lung cancer with lymphovascular invasion. J Thorac Cardiovasc Surg 2018;156:2006-2015.e2.
3. Liu W, Ren S, Zeng C, Hu Y. Prognostic value of perineural invasion in resected non-small cell lung cancer: A meta-analysis. Heliyon 2023;9:e15266.
4. Jeon H, Wang S, Song J, Gill H, Cheng H. Update 2025: Management of Non‑Small-Cell Lung Cancer. Lung 2025;203:53.
5. Kadota K, Nitadori JI, Sima CS, Ujiie H, Rizk NP, Jones DR, 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;10:806-814.
6. 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: official publication of the International Association for the Study of Lung Cancer 2022;17:362-87.
7. Travis WD, Brambilla E, Burke AP, Marx A, Nicholson AG. Introduction to The 2015 World Health Organization Classification of Tumors of the Lung, Pleura, Thymus, and Heart. J Thorac Oncol 2015;10:1240-1242.
8. Chen D, Mao Y, Wen J, She Y, Zhu E, Zhu F, et al. Tumor Spread Through Air Spaces in Non-Small Cell Lung Cancer: A Systematic Review and Meta-Analysis. Ann Thorac Surg 2019;108:945-954.

9. Willner J, Narula N, Moreira AL. Updates on lung adenocarcinoma: invasive size, grading and STAS. Histopathology 2024;84:6-17.
10. Satoshi Shiono, Naoki Yanagawa. Spread through air spaces is a predictive factor of recurrence and a prognostic factor in stage I lung adenocarcinoma, Interactive CardioVascular and Thoracic Surgery 2016;23:567–572.
11. Jia M, Yu S, Gao H, Sun PL. Spread Through Air Spaces (STAS) in Lung Cancer: A Multiple-Perspective and Update Review. Cancer Manag Res 2020;12:2743-2752.
12. Hu SY, Hsieh MS, Hsu HH, Tsai TM, Chiang XH, Tsou KC, et al. Correlation of tumor spread through air spaces and clinicopathological characteristics in surgically resected lung adenocarcinomas. Lung Cancer 2018;126:189-193.
13. Alvarez Moreno JC, Aljamal AA, Bahmad HF, Febres-Aldana CA, Rassaei N, Recine M, et al. Correlation between spread through air spaces (STAS) and other clinicopathological parameters in lung cancer. Pathol Res Pract 2021;220:153376.
14. Isgir BB, Kocaman G, Kahya Y, Ozakinci H, Elhan AH, Yuksel C. Combination of grade and spread through air spaces (STAS) predicts recurrence in early stage lung adenocarcinoma: a retrospective cohort study. Updates Surg 2025;77:201-208.
15. Jia M, Yu S, Yu J, Li Y, Gao H, Sun PL. 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;20:705.
16. Qiu X, Chen D, Liu Y, Duan S, Zhang F, Zhang Y, et al. Relationship between stromal cells and tumor spread through air spaces in lung adenocarcinoma. Thorac Cancer 2019;10:256-267.
17. Lu S, Tan KS, Kadota K, Eguchi T, Bains S, Rekhtman N, 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;12:223-234.