Clinical and Genomic Features and Prognostic Biomarkers of Oligometastatic Nonsmall Cell Lung Cancer

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INTRODUCTION: Treatment of metastatic disease is rapidly evolving with local therapies increasingly being used in patients with oligometastasis. Better personalization is needed to appropriate select patients for these interventions. We attempted to better understand clinical features and genomic features of oligometastatic nonsmall cell lung cancer (NSCLC). MATERIALS AND METHODS: Patients with metastatic NSCLC were included and underwent next generation sequencing. Patients were defined as having either oligometastatic (≤5 lesions) or polymetastatic (≥ 6 lesions) disease. Median overall survival (mOS) was computed using the Kaplan Meier method and multivariable Cox regression (MVA) analyses performed. DAVID and PANTHER analysis identified pathways differing between oligo and polymetastasis. RESULTS: A total of 406 patients were included. Oligometastasis was associated with improved mOS compared to polymetastasis (25.9 months vs. 18.7 months, P = .02) and remained so on MVA (HR 0.60, P < .001). Genetic features differed between oligometastatic and polymetastatic NSCLC. Oligometastatic patients had higher incidence of alterations in PI3K pathway genes (24.3% vs. 14.7%, P = .03) and LRPB1 (7.8% vs. 2.5%, P = .03). while polymetastatic patients had higher incidence of mutations in EGFR (33.1% vs. 21.4%, P = .01) and ALK (8.6% vs. 3.3%, P = .03). On DAVID analysis, pathways important in motility and epithelial mesenchymal transition, including WNT and TGFB, were enriched in patients with polymetastasis. CONCLUSIONS: Oligometastasis is associated with improved prognosis. The underlying genetic composition differs between oligo and polymetastasis and might aid in better defining metastatic disease with loco-regional behaviors.

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