Smesseim, I; Pennycuick, A; van Boerdonk, RA; Janes, SM; Daniels, JMA; (2025) Management of high-grade pre-invasive endobronchial lesions: To treat or not to treat? Lung Cancer , 208 , Article 108757. 10.1016/j.lungcan.2025.108757.

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Abstract

Background: High-grade pre-invasive endobronchial lesions have the potential to progress to squamous cell carcinoma (SCC), but their natural history varies. The optimal management of these lesions is controversial, with treatment strategies varying across institutions. This study aims to compare the progression free and overall survival outcomes between patients with high-grade pre-invasive endobronchial lesions who received primary treatment versus patients who were treated on progression. Methods: We conducted a retrospective cohort study across two oncology centers: University College London Hospitals (UCLH, United Kingdom) and Amsterdam University Medical Center (AUMC, The Netherlands). Patients with high-grade pre-invasive lesions underwent surveillance with repeat bronchoscopy and CT scans. At AUMC, patients routinely received endobronchial primary treatment, whereas at UCLH, treatment was reserved for cases that progressed to SCC. Primary outcome was progression-free survival (PFS), and the secondary outcome was overall survival (OS). Results: Between 1998 and 2017, 85 patients were included in the study: 34 (40 %) received primary treatment, while 51 (60 %) received treatment on progression. The latter group had a higher proportion of carcinoma in situ (CIS) compared to the primary treatment group (78.4 % vs. 38.2 %, p = 0.001) and was significantly younger (median age: 67.0 vs. 77.0 years, p = 0.001). Median overall follow-up time was 46.2 months. Primary treatment was associated with a significantly reduced risk of disease progression (HR = 0.39, 95 % CI: 0.21–0.73, p = 0.002). Median PFS was 71.0 months in the primary treatment group versus 38.0 months in the treatment on progression group (p = 0.002). Multivariate Cox regression analysis identified both primary treatment (HR = 0.47, 95 % CI: 0.26–0.87, p = 0.015) and age (HR = 1.04, 95 % CI: 1.01–1.07, p = 0.013) as independent predictors of OS. Conclusion: Our study showed that high-grade pre-invasive lesion patients who underwent primary treatment had a significantly improved PFS and OS.

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