CLINICAL UTILITY OF CIRCULATING TUMOR DNA (ctDNA) AS A PROGNOSTIC MARKER IN NON-SMALL CELL LUNG CANCER: A PROSPECTIVE COHORT STUDY

Abstract

Background: Non-small cell lung cancer (NSCLC) remains the leading cause of cancer-related mortality worldwide, with limited survival in advanced stages. Traditional prognostic markers are often invasive and insufficient for real-time disease monitoring.  Objective: To evaluate the prognostic utility of circulating tumor DNA (ctDNA) in patients with NSCLC in a tertiary care setting in Pakistan. Methods: This prospective observational study was conducted at tertiary care hospital, Lahore from December 2024 to May 2025. It included 120 histologically confirmed NSCLC patients. Peripheral blood samples were collected for ctDNA analysis using digital droplet PCR and next-generation sequencing. Baseline ctDNA detection rates were analyzed according to tumor stage and burden. Results: ctDNA was detectable in 74.2% (89/120) of patients, with positivity rates rising from 33.3% in stage II to 89.5% in stage IV disease (p < 0.001). Median ctDNA concentrations increased significantly with advancing stage. Patients with ctDNA positivity at baseline had shorter PFS (7.2 vs. 13.4 months, p < 0.001) and OS (11.8 vs. 19.6 months, p < 0.001) compared to ctDNA-negative patients. Early clearance of ctDNA during therapy was associated with improved survival, whereas persistent detection predicted poor outcomes. Multivariate analysis confirmed ctDNA positivity (HR 2.3, 95% CI 1.6–3.2, p < 0.001) as an independent predictor of poor OS. Conclusion: ctDNA is a reliable and minimally invasive prognostic biomarker in NSCLC, reflecting tumor stage, treatment response, and survival outcomes. Incorporating ctDNA into clinical practice could strengthen risk stratification and support personalized management strategies for lung cancer patients