In early-stage non-small cell lung cancer, the presence of circulating tumor DNA before surgery is not a statistically significant predictor of survival. However, detecting ctDNA after curative-intent surgery is a strong negative prognostic indicator, highlighting the critical value of post-operative testing.
Unlike immunotherapy, where ctDNA clearance strongly predicts good outcomes, chemotherapy can cause a temporary decrease in ctDNA that doesn't correlate with long-term survival. This "smudging" effect complicates ctDNA interpretation for patients receiving chemo-immunotherapy combinations.
An expert oncologist advises against ordering ctDNA tests that merely provide a "good or a bad feeling" about prognosis. The most valuable use is when a positive or negative result clearly dictates a clinical action, such as when to stop or restart adjuvant therapy.
Tumor-informed ctDNA assays, which require a tissue sample, are highly sensitive and well-suited for the adjuvant setting where tissue is available and time is less critical. In the metastatic setting, logistical challenges and the need for faster results make this approach less practical.
Data from the ADAURA trial suggests that EGFR-mutated lung cancer patients with detectable ctDNA before starting adjuvant osimertinib are at very high risk of recurrence. This finding supports considering indefinite, lifelong osimertinib for this subgroup, deviating from the standard three-year duration.