In brief
- Among 378 patients with stage 1 lung adenocarcinoma and known status for spread through air spaces (STAS), 54.2% had STAS-positive tumours, at a similar rate in EGFR-mutant and EGFR-wildtype disease.
- STAS remained independently associated with inferior disease-free survival after multivariable adjustment, with a hazard ratio of 2.32 (95% CI 1.16 to 4.63; p = 0.017).
- STAS-positive tumours were significantly associated with stage 1B disease, lymphovascular invasion, higher histological grade, micropapillary or solid predominant subtype and a PD-L1 tumour proportion score of 1% or above.
- On whole exome and RNA sequencing they were enriched for TP53 co-mutations, whole genome doubling, non-TRU transcriptomic subtypes and upregulated cell cycle pathways.
- Those molecular findings pointed the same way in EGFR-mutant and in EGFR-wildtype tumours.
Study at a glance
- Cohort: 378 patients with stage 1 lung adenocarcinoma and known STAS status
- STAS incidence: 54.2%, similar in EGFR-mutant and EGFR-wildtype tumours
- Methods: Whole exome and RNA sequencing of tumour samples with matched normal controls; disease-free survival by Kaplan-Meier method and Cox regression
- Survival: Hazard ratio 2.32 (95% CI 1.16 to 4.63; p = 0.017) after multivariable adjustment
- Histologic associations: Stage 1B disease, lymphovascular invasion, higher histological grade, micropapillary or solid predominant subtype, PD-L1 tumour proportion score 1% or above
- Molecular findings: TP53 co-mutations, whole genome doubling, non-TRU transcriptomic subtypes, upregulated cell cycle pathways
- Not reported: Overall survival and the duration of follow-up, neither of which appears in the published abstract
An adjusted hazard ratio of 2.32, on a feature present in over half the cohort
Just over half of these stage 1 tumours carried STAS, which makes it common rather than a marker of an unusual subset. Its incidence was much the same whether or not the tumour carried an EGFR mutation. It also travelled with stage 1B disease, lymphovascular invasion, higher grade, micropapillary or solid predominant subtype and a PD-L1 tumour proportion score of 1% or above, each reported as significant.
After multivariable adjustment STAS still stood on its own, with a confidence interval from 1.16 to 4.63. That interval spans a fourfold range, so the direction of the association is established while its size is not. The abstract does not name the covariates the model adjusted for, which a reader would need to judge how much of the histologic company STAS keeps is already in the estimate.
TP53 co-mutations, whole genome doubling and cell cycle upregulation
The sequencing found enrichment for TP53 co-mutations and whole genome doubling, with non-TRU transcriptomic subtypes and upregulation of cell cycle-related pathways, pointing the same way in EGFR-mutant and EGFR-wildtype tumours. In the authors’ reading those features amount to genomic instability and cell cycle dysregulation.
“STAS+ in stage 1 LUAD is associated with a distinct molecular phenotype characterised by genomic instability and cell cycle dysregulation, consistent with a more aggressive biological phenotype with implications for risk stratification and adjuvant therapy selection.”Saw et al., British Journal of Cancer (2026)
That conclusion is about which patients to pick out, and nothing here tests a treatment. No adjuvant regimen was given or compared, and no second cohort checked the molecular findings, so the work supports treating STAS as a marker worth stratifying on rather than a rule for who gets adjuvant therapy.
Sources
- British Journal of Cancer. Genomic and transcriptomic landscape of spread through air spaces in stage 1 lung adenocarcinoma (2026-09-19). doi.org
Featuring Lung Summit faculty
This study was co-authored by Lung Summit faculty Stephanie Saw.
This article was produced independently by the Lung Summit editorial team, without industry funding or input.
