Architectural Grade Combined With Spread Through Air Spaces (STAS) Predicts Recurrence and is Suitable for Stratifying Patients Who Might Be Eligible for Lung Sparing Surgery for Stage I Adenocarcinomas

Abstract

The spread through air spaces (STAS) has a main role in local recurrence of stage I lung adenocarcinomas (LAs), therefore its presence might question sublobar resection as a therapeutic option. The aim of our study was to evaluate the distribution of STAS in stage I LAs, to stratify patients according to local recurrence and to identify a group of patients who might be suitable for sublobar surgery. Patients resected with LA were included. The presence of STAS was recorded on hematoxylin eosin stained slides and clinicopathological data were obtained from medical charts. Overall survival (OS) and disease-free survival (DFS) were registered. Statistical methods included Kruskal-Wallis tests, Kaplan-Meier analyses, log-rank tests and Cox-regressions. 292 patients were included. STAS was identified in 38.7% and 95.7% of micropapillary carcinomas showed STAS. Significant correlation was found between STAS and high-grade patterns. Significant differences were found between OS and DFS estimates of STAS0 and STAS1 cases (5-y-OS: 80.0% vs. 68.4%; 5-y-DFS: 71.1% vs. 57.1%). The presence of STAS was associated with unfavorable prognosis in low and intermediate architectural grades, but not in high-grade. Multivariate analysis revealed that architectural grade (HR (OS) :2.09; HR (DFS) :1.52) and STAS (HR (OS) :1.51; HR (DFS) :1.48) were independent prognostic markers in stage I LA. Architectural grade combined with STAS was superior to other prognostic grades. The combination of architectural grade and STAS proved to be a prognostic factor that is superior to previously introduced grading systems. Patients having low and intermediate grade LAs without STAS might be eligible for sublobar resection.

The More Extensive the Spread through Air Spaces, the Worse the Prognosis Is: Semi-Quantitative Evaluation of Spread through Air Spaces in Pulmonary Adenocarcinomas

“…Shiono and Yanagawa [ 23 ] have investigated 318 patients with stage I lung adenocarcinomas and found that male gender, smoking, solid nodules, stage IB, lymphovascular and pleural invasion were associated with the STAS1. Similarly, in a previous study, we found that the STAS1 is an independent adverse prognostic factor in lobectomy specimens [ 15 ].…”

“…The ex vivo artefacts (shown in Fig. 2c ) defined in our previous publication were excluded from evaluation [ 15 ]. All patients underwent follow-up that consisted of regular physical examination, chest X-ray, abdominal ultrasonography, and chest computer tomography.…”

Impact of preoperative biopsy on tumor spread through air spaces in stage I non-small cell lung cancer: a propensity score-matched study

“…The 2021 WHO Classification of Thoracic Tumours pointed out that STAS is a histologic feature of prognostic significance [8]. Among them, STAS is an important risk factor for tumor recurrence after surgery for stage I NSCLC [9][10][11]. However, the existence of STAS has also been questioned by many scholars, who believe that STAS may be an artifact of human manipulation due to spreading caused by knife cuts during specimen processing [12], although some studies have been conducted on the specimen retrieval process and confirmed that STAS is an in vivo phenomenon that exists preoperatively and is not a result of spreading caused by specimen processing [13].…”

Proposed novel grading system for stage I invasive lung adenocarcinoma and a comparison with the 2020 IASLC grading system

“…28 STAS can be identified in both paraffin tissue and frozen sections. 29 As a powerful indicator for identifying high-risk patients, STAS has been employed by several grading systems, including those proposed by Kadota et al and Sica et al 7 In addition, our model employs a quantitative cutoff of 10% for the selected variable. This cutoff is utilized to evaluate the solid subtype, which is more straightforward to recognize than the high-grade structures containing micropapillary, cribriform, or complex glandular patterns.…”