TOPLINE:

Young adult patients with non-small cell lung cancer (NSCLC) frequently presented with adenocarcinoma and stage IV disease and showed high rates of ALK alterations. A history of smoking differentiated two distinct subgroups, with non-smokers showing more advanced disease and targetable mutations than smokers.

METHODOLOGY:

• This retrospective cohort study included 2823 patients with histopathologic diagnoses of LC at the West German Cancer Centre between 2019 and 2023.
• Patients with a first diagnosis of NSCLC not otherwise specified (NSCLC NOS), lung adenocarcinoma, lung squamous cell carcinoma, adenosquamous carcinoma, large cell neuroendocrine carcinoma, SCLC, or typical or atypical carcinoids were included.
• Patients were categorised as a young cohort (age, ≤ 45 years; n = 71) and an older cohort (age, > 45 years; n = 2682).
• The analysis included patient demographics, Eastern Cooperative Oncology Group performance status, smoking history, tumour characteristics, and molecular pathology from DNA-based next-generation sequencing panels.
• Overall survival outcomes were also assessed.

TAKEAWAY:

• Among the 71 young adult patients, 56 had a confirmed diagnosis of NSCLC or SCLC; young adult patients had a significantly better performance status at diagnosis than older patients (P < .001), with adenocarcinoma (59%) and NSCLC NOS (27%) being dominant subtypes.
• Young adult patients were significantly more likely to report no history of smoking (21% vs 6%; P < .001) and had fewer mean pack-years (33 vs 48; P = .029) than older patients.
• Higher rates of extrathoracic lymph node metastases were reported in the young cohort than in the older cohort (38% vs 14%; P = .001), with ALK translocations being significantly more common (21% vs 2.2%; P < .001), particularly in those without a history of smoking.
• Median overall survival was comparable between young and older cohorts with stage IV NSCLC (23.5 vs 29.8 months); however, overall survival was significantly improved in young adult patients with targetable genomic alterations (P = .03).

IN PRACTICE:

"In this retrospective German cohort study, the clinicogenomic characteristics of LC in young adults were characterized by adenocarcinoma histology and advanced stage at diagnosis. History of smoking differentiated two subpopulations of patients with early-onset LC: Young patients without a history of smoking often had stage IV disease at diagnosis and frequent ALK alterations," the authors wrote, adding that "a history of smoking was associated with less frequent targetable genomic alterations and lower disease stage at diagnosis in YC [young cohort]."

SOURCE:

This study was led by Maximilian Webendoerfer, Department of Medical Oncology, West German Cancer Center, University Hospital Essen, Essen, Germany. It was published online on September 24, 2025, in the European Journal of Cancer.

LIMITATIONS:

The study's single‑institution retrospective design and the rarity of early‑onset LC limited statistical interpretability and generalisability. Incomplete follow‑up and missing molecular pathology results, unreliable patient‑reported pack‑year histories, and missed forms of smoking exposure were additional limitations. Environmental and occupational risk factors were not systematically assessed or consistently documented in tumour board records and electronic medical records.

DISCLOSURES:

This study was supported by grants from the Junior Clinician Scientist Program and the Advanced Clinician Scientist Program UMEA (Medical Faculty, University of Duisburg-Essen), the Federal Ministry of Education and Research, and the German Cancer Aid (Max-Eder Junior Research Group Program). One author reported being an editor of the European Journal of Cancer. Several authors reported receiving grants and honoraria from Amgen, AstraZeneca, Bristol-Myers Squibb, GlaxoSmithKline, Janssen, Novartis, Pfizer, Roche, and Takeda. Additional disclosures are noted in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.