Potential utility of cell-free deoxyribonucleic acid for detection of early-stage resectable non-small cell lung cancer.

Authors

A Sachithanandan, P K Tan, H Mahendra-Raj, B Vivek, H H Hoh

Published in

The Medical journal of Malaysia. Volume 81. Issue 5. Pages 685-691.

Abstract

Cell-free DNA (cfDNA) has emerged as a promising non-invasive biomarker for cancer detection, including non-small cell lung cancer (NSCLC). While these approaches have demonstrated high diagnostic accuracy in controlled settings, their performance in real-world clinical populations remains uncertain. This study aimed to evaluate the diagnostic performance of a plasma cfDNA assay for early-stage NSCLC detection and to explore its association with clinicopathological parameters.
This was a single-center, crosssectional study involving 61 patients with radiologically suspected lung lesions, of whom 52 were confirmed NSCLC. Plasma samples were analyzed using a shallow genomewide sequencing-based cfDNA assay incorporating fragmentomic and copy number features. cfDNA results were compared against histopathological diagnosis to determine sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). Associations between cfDNA detection and clinical variables were evaluated using appropriate statistical tests.
The cfDNA assay demonstrated a sensitivity of 75% and a PPV of 84.8% with a specificity of 22.2% and NPV of 13.3%. cfDNA detection rates increased with advancing disease stage, although a relatively high sensitivity was observed even in stage I disease (79.4%). No statistically significant associations were found between cfDNA positivity and conventional markers of tumour burden, including tumour size, serum carcinoembryonic antigen, and SUVmax.
The cfDNA assay evaluated in this study demonstrated limited clinical utility as a standalone screening tool due to its low specificity and NPV in a realworld early-stage NSCLC population. Future efforts should focus on improving assay specificity through the incorporation of multi-omic tumour-specific biomarkers and validation that includes early-stage lung cancer cases and benign pulmonary conditions.

PMID:
42813481
Bibliographic data and abstract were imported from PubMed on 30 Sep 2026.

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