Meta-analysis links baseline and dynamic ctDNA to survival in advanced NSCLC
Photo by Logan Voss / Unsplash
Key Takeaway
Consider ctDNA monitoring as a prognostic tool in advanced NSCLC, but recognize methodological variability limits clinical use.
This systematic review and meta-analysis of 43 studies evaluated the prognostic value of plasma circulating tumor DNA (ctDNA) at baseline and its dynamics during treatment in patients with advanced non-oncogene-addicted non-small cell lung cancer (NSCLC). The primary outcome was overall survival (OS).
The meta-analysis found that detectable or elevated baseline ctDNA was significantly associated with worse OS (HR 1.62; 95% CI 1.40-1.87). Additionally, increasing or persistent ctDNA during treatment was prognostic for poor survival (HR 2.69; 95% CI 2.35-3.09). These findings suggest that ctDNA monitoring may help identify patients with worse prognosis.
However, the authors acknowledge several limitations, including substantial heterogeneity among studies, possible small-study bias, and methodological variability in ctDNA assessment. These factors reduce the certainty of the pooled estimates.
Given these limitations, clinical implementation of ctDNA-based prognostication is currently limited. Further standardization of ctDNA assays and larger prospective studies are needed before routine use can be recommended.
View Original Abstract ↓
Prognostic biomarkers for advanced non-oncogene-addicted non-small cell lung cancer (NSCLC) remain limited. This PRISMA-compliant systematic review assessed the prognostic value of plasma circulating tumor DNA (ctDNA) at baseline and its dynamics during treatment. Cochrane, EMBASE, and MEDLINE were searched to February 27, 2025, identifying studies reporting hazard ratios (HRs) for overall survival (OS). Bias was evaluated using the Quality in Prognostic Studies tool, and publication bias with funnel plots and Egger's regression. Among 7118 records, 43 studies were included, spanning diverse designs, ctDNA assays, quantification units, and definitions of dynamic change. Detectable or elevated baseline ctDNA was associated with worse OS (HR 1.62; 95 % CI 1.40-1.87) with substantial heterogeneity and possible small-study bias. Increasing or persistent ctDNA during treatment was strongly prognostic for poor survival (HR 2.69; 95 % CI 2.35-3.09). Overall study quality was moderate to high. Plasma ctDNA shows consistent prognostic value, though clinical implementation is limited by methodological variability.
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