A blood test for tumor DNA helped predict who stays cancer-free after lung surgery
Lung cancerPart of a story we are following · 9 articles · See every update
People with operable lung cancer whose tumor DNA disappeared from the blood during treatment before surgery had much longer event-free survival (hazard ratio 0.22), in the NeoCOAST-2 trial published Oct. 25, 2026, in Nature. A blood test could help guide lung cancer care.
Even after successful surgery, many people with non-small cell lung cancer see the cancer come back. Treatment before and after surgery helps, but doctors still struggle to tell who is at highest risk. One promising tool is circulating tumor DNA, or ctDNA: tiny fragments of tumor DNA that can be measured in a blood test.
What did the trial test?
NeoCOAST-2 is a phase 2 randomized platform trial in people with stage IIA to IIIB lung cancer that could be removed by surgery. Patients received standard chemotherapy plus durvalumab, an immunotherapy, combined with one of three experimental drugs: oleclumab (76 patients), monalizumab (72) or datopotamab deruxtecan, an antibody-drug conjugate (54).
What did the study find about lung cancer?
| Arm | No cancer left at surgery | Event-free at 24 months | ctDNA cleared by cycle 3 |
|---|---|---|---|
| Oleclumab | 20.3% | 70.5% | 50.9% |
| Monalizumab | 25.7% | 75.7% | 54.5% |
| Datopotamab deruxtecan | 35.2% | 77.9% | 72.5% |
Across arms, people whose ctDNA cleared had much longer event-free survival than those whose ctDNA didn’t, with a hazard ratio of 0.22. People who had both ctDNA clearance and no cancer left at surgery did best of all, with a hazard ratio of 0.10 compared with those who had neither.
Why does this matter?
A blood test taken partway through treatment could help doctors see early who is responding and who may need more or different therapy after surgery. The datopotamab deruxtecan combination had the numerically best results and deserves larger trials.
How solid is this evidence?
It’s good. Mongevity rates it B on our A-to-E scale: a randomized phase 2 trial with prespecified endpoints. Limits: the arms were small and not designed to be compared head to head, and the ctDNA analyses linking clearance to outcomes are exploratory.
What are the open questions?
Researchers need to test whether changing treatment based on ctDNA results actually improves survival, and whether the best-performing combination holds up in a phase 3 trial.
What does this mean for you?
If you or someone close to you has lung cancer that can be removed by surgery, ask about treatment before surgery and whether ctDNA testing or clinical trials are options. Not smoking remains the most important way to prevent lung cancer.
How do I explain this at dinner?
Tumors shed bits of DNA into the blood. In people treated for lung cancer before surgery, those whose tumor DNA disappeared from the blood early were much more likely to stay cancer-free. A good question for the table: what else could a simple blood test reveal?
In one sentence: in operable lung cancer, clearing tumor DNA from the blood during pre-surgery treatment was linked to much longer event-free survival.
Questions and answers
- What is ctDNA?
- Fragments of tumor DNA that circulate in the blood and can be measured with a blood test.
- What did ctDNA clearance predict?
- Much longer event-free survival, with a hazard ratio of 0.22 vs. no clearance.
- Which combination did best?
- Datopotamab deruxtecan plus chemotherapy and durvalumab had the numerically best results.
