Concurrent spread through air spaces in dominant tumours impacts prognosis in synchronous multiple primary lung adenocarcinoma.

Objectives: The impact of tumour spread through air spaces (STAS) on the prognosis of synchronous multiple primary lung adenocarcinoma (sMPLA) remains unclear. This study evaluates the prognostic significance of STAS in early-stage sMPLA and its combined effect with surgical strategies.

Methods: Patients with cT1-3N0M0 sMPLA (2012-2018) were selected based on multidisciplinary team evaluation, surgical confirmation of invasive adenocarcinoma and exclusion of metastases or minimally invasive disease. Prognostic variables were selected using the least absolute shrinkage and selection operator regression with grouped variables. Survival outcomes were analysed via Cox proportional-hazards models for overall survival and Fine & Gray competing risk regression for recurrence-free survival.

Results: Among 131 patients, STAS was observed in 68 (51.9%), including 21 (16.0%) with STAS in both tumours (bi-STAS) and 47 (35.9%) with STAS in one tumour. Bi-STAS independently predicted worse overall survival (hazard ratio = 3.78, 95% confidence interval: 1.23-11.65, P = 0.020) and recurrence-free survival (hazard ratio = 3.99, 95% confidence interval: 1.34-11.93, P = 0.013). Patients with bi-STAS had significantly lower overall survival (P < 0.001) and higher cumulative incidence of recurrence (P < 0.001) compared to mono-STAS/un-STAS groups. Notably, bi-STAS patients showed similar survival outcomes whether undergoing lobectomy or sublobar resection (overall survival: P = 0.889; recurrence-free survival: P = 0.857), underscoring limited benefit from extensive surgery.

Conclusions: Concurrent bi-STAS is a strong prognostic marker for early-stage sMPLA, independent of surgical strategy. Comprehensive STAS evaluation in all dominant tumours is critical for postoperative risk stratification.