Ultrasensitive ctDNA detection for preoperative disease stratification in early-stage lung adenocarcinoma.
Summary
In TRACERx early-stage lung cancer, an analytically validated tumor-informed ctDNA assay detected preoperative ctDNA in 81% of lung adenocarcinomas (53% in stage I). Preoperative ctDNA burden stratified prognosis, including patients with low ctDNA levels that would be missed by less sensitive methods, indicating improved risk stratification before surgery.
Key Findings
- Preoperative ctDNA detected in 81% of LUAD and 53% of pTNM stage I cases.
- Ultrasensitive assay detects ctDNA at 1–3 ppm with 99.9% specificity.
- Preoperative ctDNA levels predicted worse overall survival, improving risk stratification beyond prior assay limits.
Clinical Implications
Preoperative ctDNA could complement staging to tailor adjuvant therapy intensity, refine surveillance, and identify patients at high risk even with early-stage disease.
Why It Matters
This work demonstrates that ultra-sensitive, tumor-informed ctDNA can risk-stratify early-stage LUAD preoperatively, potentially informing adjuvant therapy and surveillance decisions.
Limitations
- Observational analysis without interventional decision-making based on ctDNA.
- Single-assay platform; external prospective interventional validation is needed.
Future Directions
Prospective trials testing ctDNA-guided adjuvant therapy and surveillance, cost-effectiveness analyses, and generalizability across healthcare systems.
Study Information
- Study Type
- Cohort
- Research Domain
- Diagnosis
- Evidence Level
- II - Prospective cohort analysis linking preoperative ctDNA to outcomes.
- Study Design
- OTHER