Spread through air spaces as a marker of nonlinear evolutionary trajectories in lung cancer: implications for the 9th edition TNM classification

Recent advancements in the diagnosis and therapeutic management of lung cancer have contributed to an evolution in pathological reporting standards. The 8th edition of the TNM classification of lung tumors has introduced the invasive size of adenocarcinoma—rather than total tumor size—as the primary determinant for staging. Concurrently, histological grading criteria proposed by the International Association for the Study of Lung Cancer (IASLC), based on predominant and highest-grade architectural patterns, appear to offer improved clinical utility over legacy systems. In addition, tumor spread through air spaces (STAS) has emerged as an actively investigated pattern of invasion, characterized by the presence of neoplastic cells beyond the main tumor mass within the adjacent pulmonary parenchyma. STAS is frequently observed in advanced-stage and node-positive non–small cell lung cancer and often correlates with distant metastasis. Recognizing its clinical relevance, the IASLC Staging Project recently recommended incorporating STAS as a histologic T descriptor in the 9th edition of the TNM classification. Expanding upon this framework, this review explores STAS not merely as a prognostic indicator, but as a potential reflection of divergent evolutionary trajectories influenced by underlying driver mutations. Accordingly, this review aims to comprehensively synthesize the prevailing controversies and recent academic milestones regarding STAS, the current limitations in preoperative STAS risk prediction, the logistical hurdles of intraoperative diagnosis, and critically evaluates the need for prospective clinical trials to validate STAS as a predictive biomarker for adjuvant systemic therapy.