Non-Small Cell Lung Cancer (NSCLC) in Young Adults, Age < 50, Is Associated with Late Stage at Presentation and a Very Poor Prognosis in Patients That Do Not Have a Targeted Therapy Option: A Real-World Study.

(1) Background: Non-small cell lung cancer (NSCLC) in young patients is uncommon. Real-world evidence on the outcomes of these patients is limited. (2) Methods: We conducted a retrospective cohort study of young NSCLC patients, age < 50 years at diagnosis, who were treated between 2011-2020 in South-East-London cancer centres. Clinicopathological characteristics, treatment and outcomes were analysed. (3) Results: Of 248 NSCLC patients, median age was 46 years, 50% ( n = 125) female, 58% ( n = 145) white, 18% ( n = 45) black and 4% ( n = 10) Asian ethnicity. Amongst patients with a documented smoking history, 30% ( n = 64) were never-smokers. Most patients had adenocarcinoma (77%, n = 191) and presented with metastatic disease (67%, n = 166). Only 31% ( n = 76) had treatment with curative intent. In patients who presented or developed metastatic non-squamous NSCLC ( n = 179), EGFR mutation status was known in 88% ( n = 157) and mutation present in 19% ( n = 34), ALK was known in 66% ( n = 118) with a translocation in 10% ( n = 18), ROS1 status was known in 57% ( n = 102) with a translocation in 4% ( n = 8), and KRAS status was known in 66% ( n = 119) with a mutation in 12% ( n = 22). Overall, 76% ( n = 152) patients with metastatic NSCLC received first-line systemic anti-cancer therapy. Median overall survival in metastatic NSCLC was 9.0 months (95% CI 6.5-11.6 months), with superior median overall survival in those with a targeted therapy option (28.7 months) compared to those without (6.6 months; p < 0.001). (4) Conclusion: Young patients contribute a significant proportion of those presenting with lung cancer. They present with advanced stage at diagnosis and have a poor prognosis. Identification of a targeted therapy option is associated with improved survival. However, most patients do not have a known genomic driver, which is in part due to limited testing, particularly in the early years of this study period. These findings highlight the particular importance of rapid-turnaround comprehensive genomic profiling in this age group and the need to identify strategies to facilitate earlier diagnosis in young NSCLC patients.