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Updated: Jun 28, 2025
Author Spotlight: Advancements in Molecular Biomarker Testing for Non-Squamous Non-Small Cell Lung Cancer
Published on: September 8, 2023
Early-Stage Non-Small Cell Lung Cancer: Prevalence of Actionable Alterations in a Monocentric Consecutive Cohort
Rossella Bruno1, Anello Marcello Poma2, Martina Panozzi1
1Unit of Pathological Anatomy, University Hospital of Pisa, Via Roma 67, 56126 Pisa, Italy.
Abstract:
Early-stage (ES) non-small cell lung cancer (NSCLC) is diagnosed in about 30% of cases. The preferred treatment is surgery, but a significant proportion of patients experience recurrence. Neoadjuvant and adjuvant chemotherapy has a limited clinical benefit. EGFR tyrosine kinase inhibitors and immunotherapy have recently opened new therapeutic scenarios. However, only a few data are available about the ES-NSCLC molecular landscape and the impact of oncogene addiction on therapy definition. Here, we determined the prevalence of the main lung cancer driver alterations in a monocentric consecutive cohort. Molecular analysis was performed on 1122 cases, including 368 ES and 754 advanced NSCLC. The prevalence of actionable alterations was similar between early and advanced stages. ES-NSCLC was significantly enriched for MET exon-14 skipping alterations and presented a lower prevalence of BRAF p.(V600E) mutation. PD-L1 expression levels, evaluated according to actionable alterations, were higher in advanced than early tumors harboring EGFR, KRAS, MET alterations and gene fusions. Taken together, these results confirm the value of biomarker testing in ES-NSCLC. Although approved targeted therapies for ES-NSCLC are still limited, the identification of actionable alterations could improve patients' selection for immunotherapy, favoring the enrollment in clinical trials and allowing a faster treatment start at disease recurrence.
Insights
Biomarker testing is crucial for early-stage non-small cell lung cancer (NSCLC). Identifying specific genetic alterations like MET exon-14 skipping can guide immunotherapy selection and improve treatment strategies.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Early-stage non-small cell lung cancer (NSCLC) often recurs after surgery, with limited benefit from traditional chemotherapy.
- Novel therapies like EGFR tyrosine kinase inhibitors and immunotherapy offer new treatment avenues.
- Understanding the molecular landscape of early-stage NSCLC is vital for optimizing treatment selection.
Purpose of the Study:
- To determine the prevalence of key driver alterations in a cohort of early-stage (ES) and advanced non-small cell lung cancer (NSCLC) patients.
- To investigate the impact of oncogene addiction on therapy definition in ES-NSCLC.
- To compare molecular profiles and PD-L1 expression between early and advanced NSCLC stages.
Main Methods:
- Molecular analysis of 1122 NSCLC cases (368 early-stage, 754 advanced).
- Assessment of common lung cancer driver alterations, including EGFR, KRAS, MET, and BRAF mutations.
- Evaluation of PD-L1 expression levels in relation to actionable alterations.
Main Results:
- Actionable alteration prevalence was similar in early and advanced NSCLC.
- ES-NSCLC showed enrichment for MET exon-14 skipping alterations and lower BRAF p.(V600E) mutation rates.
- Higher PD-L1 expression was observed in advanced tumors with EGFR, KRAS, MET alterations, and gene fusions compared to early-stage tumors.
Conclusions:
- Biomarker testing is valuable for ES-NSCLC, revealing specific actionable alterations.
- Identifying these alterations can aid patient selection for immunotherapy and clinical trials.
- This molecular insight supports earlier treatment initiation, especially upon disease recurrence.
