Spread through air spaces in multiple synchronous bilateral primary lung cancer: prognostic implications in a surgical cohort

OBJECTIVE: The surgical treatment of multiple synchronous bilateral primary lung cancer (mSBPLC) showed promising results and the aims of this retrospective study were to assess the oncologic outcomes and the presence of risk factors of worse survival. METHODS: Patients underwent radical (all lesions removed) lung resection for mSBPLC from 2017 to 2024 were included. Exclusion criteria: patients unfit for bilateral surgery, pneumonectomy, multifocal ground glass opacities, clinical stage IIIA or more and pre-operative treatment. Overall and disease-free survival analyses were conducted with the Kaplan-Meier method and log-rank test, Cox regression analysis was used to identify the predictors of worse survival. RESULTS: During the study period, 64 patients were screened for the presence of bilateral lung nodules, 45 patients (median age 69 years) were operated for mSBPLC and during the follow-up (median 34 months) we observed 11 deaths and 15 cancer recurrence. In the 80% of patients the main cancer was solid, contralateral was a part-solid in 20% or pure ground glass opacity in 20%. Adenocarcinoma was present in 77.8% at first surgery and in 80% at the second. Spread Through the Air Spaces (STAS) was present in 17.8%. The 5 year overall and disease-free survival rate were 77% (median 86 months -CI95% 72.4-99.5-) and 57% (median 69 months -32-105.9-), respectively. Comparing survivals among patients with and without STAS, we had an overall survival of 0% vs 85% (86 vs 29 months, p < 0.01) and a disease-free survival of 0% vs 63% (69 vs 9 months, p < 0.01). The multivariable analysis demonstrated STAS as significant predictor of worse overall (HR 7.08, p = 0.02) and disease-free survival (HR 5.63, p = 0.017). CONCLUSIONS: Taking into account the small and highly selected study population, staged bilateral surgery could be considered safe and oncologically adequate, showing the association between the presence of STAS and unfavourable long term outcomes.