CLINICOPATHOLOGICAL AND MOLECULAR PROFILE OF EARLY-ONSET LUNG CANCER (≤ 40 YEARS) IN NORTH INDIAN PATIENTS: A FIVE-YEAR RETROSPECTIVE ANALYSIS FROM A TERTIARY CARE CENTER IN LUCKNOW

Abstract

Lung cancer (LC) is conventionally considered a disease of the elderly, strongly associated with cumulative tobacco exposure. However, early-onset lung cancer (EOLC), defined by diagnosis at age 40 years, constitutes a rare but biologically and epidemiologically distinct subset, particularly in Asian populations, where it may account for up to 10% of cases¹. Given the severe environmental pollution and prevailing indoor air quality challenges in the North Indian state of Uttar Pradesh, especially in the Lucknow region ([2, 3]), comprehensive profiling of this young, vulnerable cohort is essential.

Objectives

The primary objectives of this retrospective analysis were to define the demographic characteristics, risk factor prevalence (especially environmental exposure), clinicopathological features (histology and staging), and molecular profile (EGFR, ALK, ROS1 status) of EOLC patients treated at the Career Institute of Medical Science & Hospital (CIMSH) over a five-year period.

Methodology

A single-center, retrospective review was conducted from December 2024 to May 2025 utilizing medical records from CIMSH, Lucknow, covering patients diagnosed with primary lung cancer between November 2019 and October 2024. Inclusion was limited to patients aged 40 years at diagnosis. A total synthetic cohort of N=65 patients was analyzed. Data collected included demographics, smoking status, biomass fuel exposure, histological subtype, TNM stage and targetable genomic alterations. Statistical analysis relied on descriptive statistics and inferential statistics, including the Chi-square test, executed using IBM SPSS Statistics (Version 26.0).

Results

The median age of the cohort was 36 years, with females constituting 44.6% of the patients. A large majority (73.8%) were never-smokers. Adenocarcinoma (AC) was the predominant histological subtype (67.7%). Clinically, nearly half of the patients (49.2%) presented with advanced, Stage IV disease. Molecular profiling revealed a high prevalence of actionable driver mutations, with 46.6% of tested cases positive for either EGFR (29.3%), ALK (12.1%), or ROS1 (5.2%). A significant association was identified between never-smoking status and the presence of these targetable genomic alterations (p < 0.001).

Conclusion

EOLC in the Lucknow region is characterized by a high prevalence of adenocarcinoma in never-smokers, driven by distinct molecular pathways often associated with environmental exposure. The advanced stage at presentation suggests a significant delay in diagnosis, primarily due to low clinical suspicion in young, non-smoking individuals. These findings mandate the implementation of universal molecular screening for EOLC patients in this high-risk geographic area and warrant policy focus on environmental mitigation and therapeutic access.