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Lung Cancer Treatments and Mutations / Lung Cancer Diagnosis and Treatment / Multiple and Secondary Primary Cancers · Journal article
Frontiers in Oncology · August 12, 2026
Well-designed and adequately powered for the question it asks.
This multicenter propensity-matched cohort study of 6,883 lung cancer patients demonstrates that early-onset lung cancer (age <50 years), despite presenting with more aggressive features (higher stage IV, bone and brain metastases), is associated with superior survival compared to late-onset disease. The survival advantage and distinct mutational profile (notably higher HER2 mutation rate at 10.1% vs 1.6%) suggest different biology and warrant targeted investigation of early-onset lung cancer as a distinct clinical entity.
Multicenter retrospective cohort study with propensity score matching. Lung cancer patients aged 18–74 years diagnosed at 26 hospitals in Chongqing between January 2019 and December 2022.. Intervention: Early-onset lung cancer (age <50 years at diagnosis). Compared with: Late-onset lung cancer (age ≥50 years at diagnosis). n = 6,883. 26 hospitals in Chongqing, China.
6,883 total patients: 690 EOLC (age <50) and 6,193 LOLC (age ≥50) Median overall survival: 42.7 months EOLC versus 32.9 months LOLC after propensity matching 5-year survival rates: 42.2% EOLC versus 35.4% LOLC
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Clinicians should recognize early-onset lung cancer as a distinct entity with superior prognosis despite more aggressive initial presentation. The high HER2 mutation enrichment in early-onset patients warrants targeted genetic testing and tailored therapeutic strategies, potentially including HER2-directed therapies, for this younger population.
Multicenter retrospective cohort study with propensity score matching comparing 690 early-onset and 6,193 late-onset lung cancer patients, reporting clinically meaningful survival differences and tumor biology features across clearly defined groups.
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Clinicians should recognize early-onset lung cancer as a distinct entity with superior prognosis despite more aggressive initial presentation. The high HER2 mutation enrichment in early-onset patients warrants targeted genetic testing and tailored therapeutic strategies, potentially including HER2-directed therapies, for this younger population.
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Introduction The characteristics of early-onset lung cancer (EOLC) have not been extensively studied. Our research aimed to comprehensively assess the clinicopathological, genetic features and prognosis of EOLC. Materials and methods In this retrospective study of lung cancer patients diagnosed at 26 Chongqing hospitals between January 2019 and December 2022 (18-74 years), we stratified them into early-onset lung cancer ( 50 years) and late-onset lung cancer (≥50 years) groups. Furthermore, we used propensity score matching to balance baseline characteristics, compare overall survival and lung cancer-specific survival between early-onset lung cancer (EOLC) and late-onset lung cancer (LOLC) groups, and perform subgroup comparisons. Results A total of 6,883 lung cancer patients were included in the final analysis, comprising 690 patients with EOLC and 6,193 patients with LOLC. Compared with the LOLC group, the EOLC group had more females and never-smokers. In clinical features, EOLC patients predominantly had adenocarcinoma (69.7% vs. 52.2%), more often presented with stage IV disease (49.3% vs. 44.0%), and had higher rates of bone (22.8% vs. 16.9%) and brain metastases (18.4% vs. 10.8%), yet were more likely to undergo surgery (31.0% vs. 22.4%). Significant differences in mutation rates were observed for HER2 (10.1% vs. 1.6%). After propensity score matching, late-onset was identified as an independent risk factor for adverse survival outcomes, the median overall survival was 42.7 months for EOLC versus 32.9 months for LOLC, with 1-, 3-, and 5-year survival rates of 78.0%, 54.4%, and 42.2% in the EOLC group, compared with 75.5%, 47.8%, and 35.4% in the LOLC group. Conclusions Despite more aggressive clinicopathological features, EOLC was associated with better survival outcomes. Moreover, distinct driver gene alteration profiles highlight the need to identify targetable alterations and implement targeted therapy in this enriched population.
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