ctDNA positivity Linked to Worse Outcomes in Non-Small Cell Lung Cancer, Major Review Confirms
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A new meta-analysis reveals that the presence of circulating tumor DNA (ctDNA) is consistently associated with poorer survival rates and a higher risk of recurrence in patients with non-small cell lung cancer (NSCLC), reinforcing the potential of liquid biopsies to improve cancer management.
Despite advancements in treatment, many patients with stage I to III NSCLC still face disease progression and low five-year survival rates. current methods for monitoring treatment response, like imaging, don’t always align with invasive pathological findings, highlighting the need for more accurate, non-invasive biomarkers. ctDNA sequencing has emerged as a promising tool for detecting minimal residual disease, offering a potential solution to these challenges.
The Promise of Liquid Biopsies
ctDNA fragments, originating from tumor cells, carry unique genetic facts that can be used for early diagnosis, risk assessment, and tracking disease progression across various cancers. Researchers have noted that ctDNA testing is more sensitive, less invasive, and potentially more cost-effective than traditional methods. However, previous studies often focused on specific stages or outcomes, leaving a gap in understanding its broader role in NSCLC treatment.
To address this, investigators conducted a comprehensive systematic review and meta-analysis of global research, examining ctDNA detection at multiple time points and its correlation with key prognostic indicators. The team analyzed data from 52 eligible studies – including 5,788 patients – to assess the impact of ctDNA status on overall survival (OS) and recurrence-free survival (RFS).
Key Findings
The analysis revealed a meaningful association between ctDNA positivity and worse outcomes. Patients with detectable ctDNA faced a 1.74-fold increased risk (95% CI, 1.49-2.03) of death compared to those with negative ctDNA, even when accounting for disease stage. This increased risk was observed in both patients with resectable and unresectable disease.These trends continued post-treatment, with substantially worse OS observed in both resectable and unresectable patients with persistent ctDNA.
The increased risk of recurrence extended across all NSCLC subtypes. Patients with positive ctDNA had a 1.67-fold higher recurrence risk at baseline (95% CI, 1.27-2.20), increasing to 3.13-fold after treatment (95% CI, 2.09-4.67) and 5.42-fold during long-term surveillance (95% CI,3.20-9.18). Notably, the median time between ctDNA detection and radiographic or clinical recurrence was just 2.93 months (range, 1.70-12.60).
Future Directions and Limitations
The researchers acknowledge limitations in their analysis, including significant variability across studies and the prevalence of small, retrospective designs. Despite these caveats, they express confidence in their findings and emphasize the potential of ctDNA-based liquid biopsies to refine risk stratification and personalize treatment decisions.
“These findings underscore the potential of ctDNA-based liquid biopsy to refine risk stratification, guide individualized treatment decisions, and ultimately improve clinical outcomes in NSCLC,” the authors concluded. “Prospective trials with standardized methodologies are warranted to further substantiate these clinical benefits.”
These results highlight the need for further investigation into ctDNA as a powerful tool in the fight against NSCLC, potentially leading to earlier interventions and improved outcomes for patients.
References
Chen X, Zhang M, Zhou Q, et al. Circulating tumor DNA as prognostic markers of non-small cell lung cancer (NSCLC): a systematic review and meta-analysis. Transl Lung Cancer Res. 2025;14(12):5491-5508. doi:10.21037/tlcr-2025-900
Schmid S, Jochum W, Padberg B, et al. How to read a next-generation sequencing report-what oncologists need to know. ESMO Open. 2022;7(5):100570. doi:10.1016/j.esmoop.2022.100570
