The presence of tumor spread through air spaces (STAS) demonstrated an association with poor prognosis in patients with early-stage non–small cell lung cancer (NSCLC), whether undergoing segmentectomy or lobectomy, according to findings from an analysis of the phase III JCOG0802/WJOG4607L trial presented at the International Association for the Study of Lung Cancer (IASLC) 2025 World Conference on Lung Cancer (WCLC; Abstract PL03.16).
“Our study confirms that STAS is a powerful prognostic marker in early-stage NSCLC and should be considered when planning surgical and follow-up strategies,” said Yasushi Yatabe, MD, PhD, of the Department of Diagnostic Pathology at the National Cancer Center, Japan. “The findings emphasize the importance of integrating detailed pathologic review into treatment decision-making.”
Background and Study Methods
STAS occurs when tumor cells float in the air spaces of the lung, or the alveoli, beyond the primary tumor mass, allowing for the growth of new tumors. Additionally, STAS can only be identified under a microscope and not by CT scan.
The JCOG0802/WJOG4607L study was a noninferiority, randomized, multicenter phase III trial of segmentectomy vs lobectomy surgical approaches in patients with T1aN0 NSCLC. In an analysis from the trial, researchers explored the association between STAS and clinical outcomes in a subset of patients with nonmucinous adenocarcinoma.
Thirty-two pathologists from the IASLC Pathology Committee across 15 countries looked at slides from all of the study participants. Each case was digitized with NanoZoomer 360 and reviewed by three pathologists for histologic features of STAS and histologic grade. Six cases were excluded from the analysis, making 640 patients eligible for analysis within the review of surgery type, and 487 eligible within the nonmucinous adenocarcinoma subgroup.
Key Study Findings
STAS was found in 35.5% of patients and was associated with a significant shorter relapse-free survival (hazard ratio [HR] = 2.050; 95% confidence interval [CI] = 1.462–2.874; P < .001) and overall survival (HR = 2.340; 95% CI = 1.704–3.212; P < .001).
Multivariable Cox regression analysis determined that STAS presence was an adverse prognostic marker for both relapse-free survival (P < .001) and overall survival (P = .004).
STAT-positive tumors had higher frequencies of local recurrences than STAS-negative tumors, leading to poor patient relapse-free and overall survival outcomes in both the lobectomy and segmentectomy subgroups.
By multivariable analysis, the presence of STAS was associated with a statistically significantly poor prognosis for relapse-free survival in both the lobectomy (P = .007) and segmentectomy subgroups (P = .006) and for overall survival in the lobectomy subgroup (P = .019).
In the subset of patients with nonmucinous adenocarcinoma, histologic grade 3 was strongly associated with STAS presence (P < .001) and worse outcomes by relapse-free survival (HR = 2.977; P < .001) and overall survival (HR = 2.797; P < .001). By multivariable analysis, both STAS presence (P = .021) and histologic grade 3 (P = .001) were independently associated with prognosis for shorter relapse-free survival, but only histologic grade was significantly associated with overall survival (P = .002).
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