Spread through air spaces (STAS) in stage I lung adenocarcinoma under the new IASLC/WHO pathological grading system: research progress on prognostic value-narrative review.
Abstract
Background and objective Despite complete surgical resection, stage I lung adenocarcinoma exhibits a postoperative recurrence rate of 15-27%, exposing the prognostic limitations of the current Tumor Node Metastasis (TNM) staging system. While the 2020 International Association for the Study of Lung Cancer (IASLC) three-tier grading system significantly improves risk stratification based on high-grade morphological components, it does not incorporate tumor spread through air spaces (STAS), a recognized independent adverse prognostic factor. This review aims to systematically examine the incremental prognostic value of STAS within the framework of the new IASLC grading system and explore its clinical implications. Methods A comprehensive literature search was conducted using the PubMed database to retrieve relevant English-language studies. The review synthesized evidence focusing on the distribution of STAS across histological subtypes, its dose-response relationship with high-grade components, its impact on surgical decision-making, and the critical diagnostic distinction between true STAS and ex vivo artifacts. Key content and findings Current evidence reveals a significant dose-response relationship between STAS and high-grade patterns; notably, the presence of even 5% high-grade components substantially elevates the risk of STAS. Retrospective cohorts consistently demonstrate that STAS strongly predicts disease-free survival and is a critical risk factor for local recurrence following sublobar resection. Crucially, STAS-positive IASLC Grade 2 tumors exhibit recurrence risks overlapping with those of Grade 3, supporting an "upstaging hypothesis" that warrants prospective validation. Furthermore, the clinical translation of STAS remains constrained by the high false-negative rates of intraoperative frozen sections and the ongoing debate regarding artifactual floaters. Conclusions Integrating STAS status as a collaborative parameter with the IASLC grading system constitutes a conceptual synthesis rather than an established clinical framework for stage I lung adenocarcinoma without necessitating additional molecular testing. Because the current evidence is based predominantly on retrospective data, prospective randomized controlled trial (RCT) validation is required before this approach can be regarded as best clinical practice.
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