When doctors follow cancer over time, they’re really asking a few simple questions:
For some cancers, there are special blood tests that help answer these questions. These are often called “tumor markers.” They’re substances made by cancer cells (or by the body in response to cancer) that can go up when cancer is active and down when it responds to treatment.
Examples include CA-125 for some ovarian cancers, CEA for some colon cancers, and CA-19-9 for some pancreatic cancers. Doctors may check these along with scans to see whether treatment is working or to watch for cancer coming back. Natera
But these markers have big limits:
Because of that, cancer has mainly been followed with imaging — CT, PET, MRI, mammograms, and ultrasounds. These are crucial, but they often take months to show change. They can also miss very tiny amounts of cancer, sometimes called microscopic or minimal residual disease (MRD).
Over the last few years, a newer blood test has started to fill in some of these gaps: circulating tumor DNA, usually shortened to ctDNA.
Cancer cells are messy. As they grow and die, tiny bits of their DNA break off and float in the bloodstream. That cancer-specific DNA is called circulating tumor DNA (ctDNA).
A ctDNA test is just a blood draw. The lab then:
In simple terms:
Scans show what is big enough to see.
ctDNA tries to show what is starting to happen long before a lump or spot shows up on a scan.
ctDNA doesn’t replace scans or exams. It’s another lens — one that can be more sensitive and faster to change.
You may hear about two broad types of ctDNA tests:
At Sagely Health, when a ctDNA test makes sense, we often suggest that people and their oncologists consider a test like Guardant360. It:
We don’t sell these tests or get paid by the companies. Our role is to help patients and families understand results and think through what they might mean for next steps.
Below are examples, by cancer type, of how ctDNA has been used in real studies. Over time, more studies will be added under each heading.
In a community radiation oncology practice, women with early-stage but high-risk breast cancer had ctDNA checked regularly after they finished surgery, radiation, and other treatments. Natera
For many who later had a relapse, ctDNA turned positive first, sometimes months before anything was seen on scans. In others, ctDNA went from positive to negative after new treatment, matching how well they were doing. There were a few tricky cases — a false negative, and a new second cancer that didn’t show up on the original ctDNA test — which is a good reminder that ctDNA is powerful but not perfect.
For a patient, this kind of work says: even when you feel “done” with treatment, ctDNA might help flag hidden cancer earlier than scans alone, and might one day guide who needs extra treatment and who might safely avoid it.
Read the abstract / summary:
Natera
In the large I-SPY2 trial, patients with high-risk early breast cancer (including triple-negative and high-risk hormone-receptor–positive disease) had ctDNA checked at key points: before treatment, during chemotherapy, and after it was finished. Targeted Oncology
Women whose ctDNA stayed detectable after treatment had a much higher chance of the cancer coming back far from the breast, even if their surgery showed no obvious tumor left (a “pathologic complete response”). Women whose ctDNA became and stayed undetectable tended to do better over the long term.
For patients, this suggests ctDNA might help separate people who are truly low risk after treatment from those who still have a higher risk, even when the breast looks clear and the surgery report is good.
Read the abstract / summary:
Targeted Oncology
In the c-TRAK TN study, women with triple-negative breast cancer who had finished standard treatment were followed closely with ctDNA. If ctDNA turned positive, it was often the first sign that cancer was returning. Many already had tiny metastases by the time the blood test flipped, even before they felt symptoms or had clear scan findings. PubMed+1
The message from this work is that, in aggressive subtypes like triple-negative disease, ctDNA can act like an early alarm. Future trials are asking: if we start treatment as soon as ctDNA turns positive, can we change the course of the disease?
Read the abstract:
PubMed
For people with RET fusion–positive non–small-cell lung cancer (NSCLC), drugs like pralsetinib can work very well. In follow-up work from the ARROW study and related research, ctDNA has been used to track how well this kind of targeted therapy is working and how resistance develops. PubMed+1
When treatment is working, the amount of RET-mutant ctDNA in the blood often drops sharply or becomes undetectable. When the cancer starts to find ways around the drug, new mutations can sometimes be seen first in the blood — long before a big change shows up on scans. That information can then guide switches to other trials or combinations.
For patients, this turns ctDNA into a kind of early scorecard on how well a targeted pill is doing, and a way to catch resistance sooner.
Read the main trial paper:
PubMed
In a large real-world study of people with NSCLC and small-cell lung cancer (SCLC), researchers looked at something called tumor fraction — the percentage of DNA in the blood that appears to come from cancer. PubMed+1
Patients had ctDNA checked about 6–15 weeks after starting treatment (immunotherapy, targeted therapy, or chemo). Those whose tumor fraction fell a lot tended to live longer and have better control of their cancer. Those whose tumor fraction stayed high or went up often had worse outcomes, even if their scan at that moment didn’t look dramatically different.
This suggests that, across lung cancers, ctDNA can give an early read on whether a new treatment is helping — sometimes faster than scans.
Read the abstract:
PubMed
In the INTERCEPT-TT program, people with colorectal cancer who had finished surgery and standard chemo still had positive ctDNA — a sign of tiny leftover disease that scans couldn’t see. They were given an oral chemo pill called TAS-102 and followed over time. PubMed+2Natera+2
A key question was: can this extra treatment make ctDNA turn negative and delay or prevent the cancer from coming back? Early results suggest that, for a meaningful share of patients, ctDNA did clear with TAS-102, while very few similar patients who were just watched saw their ctDNA clear on its own. Those who cleared ctDNA tended to stay in remission longer.
For someone who has “no evidence of disease” on scans but still has positive ctDNA, this kind of work hints that additional treatment may be worthwhile — and that ctDNA itself can be used as a target to aim for.
Read the abstract:
PubMed
The DYNAMIC-III trial enrolled people with stage III colon cancer after surgery. Everyone had a ctDNA test about 5–6 weeks after surgery. One group had standard chemo decisions (based on stage and risk). The other group had chemo intensity guided by ctDNA:
The ctDNA-guided group ended up using less oxaliplatin, with similar outcomes overall, and ctDNA still clearly separated people at higher vs lower risk. This means many patients with no ctDNA detected might safely avoid some of the extra chemo and side effects, while those with positive ctDNA may need more than our current drugs can offer and should be prioritized for new options and trials.
Read the paper:
Nature
In a large real-world program called INTERCEPT, patients with colorectal cancer were followed with serial ctDNA tests after treatment. ctDNA-positive patients had a much higher chance of relapse than ctDNA-negative patients, regardless of stage. In fact, some stage IV patients who were ctDNA-negative after treatment did better than stage II patients who were ctDNA-positive. ResearchGate
This supports an idea patients often feel intuitively: what is happening now in your body can matter more than what stage you were months or years ago. ctDNA gives a way to see that.
Read the abstract / poster:
ResearchGate
For locally advanced rectal cancer, many patients now receive chemotherapy and radiation before surgery. A portion of them have such a strong response that no clear tumor is left. This raises a huge question: do they still need major rectal surgery, or can some safely enter a “watch and wait” program?
Recent work has shown that ctDNA can help refine that choice. In one study, patients with locally advanced rectal cancer who had finished “total neoadjuvant therapy” had ctDNA checked. Those with no ctDNA detected after treatment tended to do better and were more likely to stay free of recurrence, supporting the idea that some could be monitored closely without immediate surgery. Those with positive ctDNA had higher risk and may need surgery or additional therapy. PMC+2Natera+2
Read one of the key papers:
PMC
In metastatic pancreatic ductal adenocarcinoma (PDAC), time matters. One ongoing phase II trial is testing an approach where everyone starts on a strong chemo combination called modified FOLFIRINOX. ctDNA is checked regularly. If ctDNA doesn’t fall as hoped, patients switch early to gemcitabine plus nab-paclitaxel rather than waiting for obvious growth on scans. Cancer.gov+1
The idea is simple but powerful: if the blood test shows the first regimen isn’t working, don’t waste cycles and side effects on it. Move sooner to something that might help more. Results are still early, but this trial shows how ctDNA can be used as a real-time guide in a cancer where every week counts.
Read the trial description:
Cancer.gov
Some people with clear-cell kidney cancer have only a few spots of disease in the body. In a phase II trial from MD Anderson, these patients received focused radiation (SABR) to all visible spots and did not start systemic therapy right away. They were followed with scans and with a ctDNA test that could pick up tiny traces of cancer. The Lancet+2MD Anderson Cancer Center+2
Patients with no ctDNA detected after radiation stayed off systemic drugs about twice as long as those whose ctDNA was still positive. Overall, many went close to three years without needing pills or infusions, with excellent survival.
For patients, this suggests that, when disease is limited and can be zapped with radiation, ctDNA might help decide who can safely wait before starting systemic therapy and who needs it sooner.
Read the news summary and scientific paper:
MD Anderson Cancer Center
In muscle-invasive bladder cancer, many patients have their bladder removed (cystectomy). The big question afterward is who needs extra treatment to prevent relapse.
The IMvigor011 trial used a tumor-informed ctDNA test after surgery:
In ctDNA-positive patients, atezolizumab improved both disease-free survival and overall survival compared with placebo. In ctDNA-negative patients, outcomes were very good with observation alone, suggesting many did not need additional drugs.
This is one of the clearest examples so far of ctDNA being used to aim treatment where it’s most needed and spare it where it likely adds little.
Read the NEJM paper:
New England Journal of Medicine
Across all these cancers, ctDNA is doing things traditional markers and scans cannot:
At the same time, ctDNA has limits:
For you as a patient or caregiver, the most useful step is not to memorize trial names, but to know this tool exists and to ask good questions, such as:
If you already have ctDNA results or are thinking about testing, Sagely Health can help you make sense of what they might mean and what questions to bring back to your oncologist — including whether there are clinical trials built around these newer, more sensitive ways of tracking cancer.
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