Lung Cancer in Younger Adults without Targetable Mutations Associated with Poor Prognosis

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The leading cause of cancer-related deaths worldwide is lung cancer, which accounted for 1.8 million deaths in 2020. The 5-year survival rate in patients with lung cancer is poor, with advanced cases of non–small-cell lung cancer (NSCLC) accounting for up to 90% of all cases. The average median age at diagnosis is 72 years in the United Kingdom, and people <50 years of age made up 2.5% of all cases in 2020. Although the rate of tobacco smoking in younger adults is decreasing in the United Kingdom, the incidence rate of NSCLC has remained steady since the early 2000s. Younger patients are more likely to be female, have lower smoking rates, and to be diagnosed at an advanced stage.

Research indicates that air pollution in urban areas may play a role in this steady incidence rate. When particulate matter increases, the risk of epidermal growth factor–receptor (EGFR) NSCLC increases, especially in people who have never smoked. Anaplastic lymphoma kinase (ALK) and ROS proto-oncogene 1 (ROS1) mutations along with the EGFR mutation are more common in NSCLC occurring in younger patients. These 3 genetic alterations have targeted treatments that have been found to improve patient survival. In a large US study of young patients with NSCLC, poor survival outcomes were described despite targetable mutations, suggesting aggressive disease may be occurring in younger patients. However, another study with a predominant Asian population suggested better survival of younger patients versus older patients with NSCLC.

A retrospective study of 248 young patients with NSCLC aged <50 years in the United Kingdom explored real-world outcomes. The median patient age was 46 years: 9 patients were aged 18 to 30 years, 52 patients were aged 31 to 40 years, and 187 patients were aged 41 to 50 years. When patients’ smoking history was examined, it was found that 30% had never smoked. The sex ratio was even, which is a higher than expected proportion of women to men. White patients comprised 58% of the study population, 18% of patients were Black, and 4% were Asian. Adenocarcinoma was the predominant cancer type at 77%, 13% had squamous-cell carcinoma, 8% had NSCLC not otherwise specified, and 1% had large-cell carcinoma. Advanced metastatic NSCLC was found in 67% of patients.

The EGFR mutation was found in 34 patients, 18 patients had the ALK mutation, 8 patients had the ROS1 mutation, and 22 had the KRAS mutation. First-line therapy was received by 152 patients with metastatic NSCLC, with only 30% of patients receiving treatment with a curative intent. The median overall survival in patients with metastatic NSCLC was 9.0 months. Patients who had targeted therapy had a median overall survival of 28.7 months, and those who did not had an overall survival of 6.6 months.

Source: Hughes DJ, Kapiris M, Podvez Nevajda A, et al. 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. Cancers (Basel). 2022;14(24):6056.

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