Multidisciplinary Perspective of Spread Through Air Spaces in Lung Cancer: A Narrative Review

Spread Through Air Spaces (STAS) is an emerging pattern of tumor invasion in lung cancer, first recognized by the World Health Organization in 2015. This narrative review examines STAS from a multidisciplinary perspective, integrating pathologic, radiologic, oncologic, and surgical points of view, together with molecular biology to assess its clinical significance, diagnostic challenges, and therapeutic implications. Pathologically, STAS is characterized by tumor cells floating beyond the main tumor, contributing to recurrence and poor prognosis. Radiologic advancements suggest potential imaging markers for STAS, such as spiculation, the absence of an air bronchogram, solid tumor components, as well as high fluorodeoxyglucose uptake, though definitive preoperative identification remains challenging. Oncologic studies link STAS to aggressive tumor behavior and lympho-vascular invasion, suggesting a role for adjuvant chemotherapy even in the earliest stages of disease; furthermore, specific molecular alterations have been discovered, including EGFR wild-type status and ALK/ROS1 rearrangements together with high Ki-67 expression, tumor necrosis, and alterations in cell adhesion proteins like E-cadherin. Surgical aspects highlight the increased risk of recurrence following limited resection, raising concerns about optimal surgical strategies. The debate over STAS as a true invasion mechanism versus an artifact from surgical handling underscores the need for standardized pathological evaluation. This review aims to refine STAS detection, integrate it into multidisciplinary treatment decision-making, and assess its potential as a staging criterion in lung cancer management.