For people with locally advanced rectal cancer, completing chemotherapy and radiation is a major milestone, but it is rarely the end of the journey. After treatment, patients and their doctors face a difficult question: Has the cancer truly been eliminated, or do microscopic cancer cells remain in the body?
Today, doctors rely on MRI scans, endoscopy, biopsies, and physical examinations to answer that question. These tools are highly effective, but they are not perfect. Sometimes, cancer cells remain even when there is no visible sign of disease.
Now, researchers say a simple blood test may help fill that gap. A new study found that testing for circulating tumor DNA (ctDNA) after treatment was highly effective at identifying patients whose rectal cancer was likely to return. The findings suggest ctDNA could one day become an important tool for helping doctors personalize treatment and follow-up care.
What Is ctDNA?
Cancer cells constantly grow, divide, and die. As they do, they release tiny fragments of their DNA into the bloodstream. These fragments are called circulating tumor DNA (ctDNA).
Using highly sensitive technology, doctors can search a blood sample for these fragments after cancer treatment. If ctDNA is detected, it may mean that microscopic cancer cells are still present somewhere in the body, even if imaging scans cannot yet see them. If ctDNA is not detected, it suggests treatment has been successful, although it does not guarantee that the cancer will never return. Because ctDNA reflects what is happening throughout the body, many researchers believe it may offer information that complements traditional imaging rather than replacing it.
Why Is This Important for Rectal Cancer?
People with locally advanced rectal cancer are typically treated with chemotherapy, radiation therapy, or both before surgery. This is known as neoadjuvant therapy, and its goal is to shrink or eliminate the tumor before surgery.
Some patients respond so well that no visible tumor remains after treatment. Rather than proceeding directly to surgery, which usually involves removing part or all of the rectum, these patients may choose non-operative management, often called a watch-and-wait approach. Instead of immediate surgery, they undergo frequent scans, endoscopy, and physical examinations to watch for signs that the cancer has returned. The challenge is that current tests cannot always detect tiny amounts of remaining cancer. Researchers wanted to know whether ctDNA could provide an earlier and more accurate picture of who was truly cancer-free.
Inside the Study
The study included 220 people with stage II or III rectal cancer treated at multiple medical centers between 2018 and 2024. All participants first received neoadjuvant therapy. Afterward, 148 patients underwent surgery, and 72 patients entered a watch-and-wait program without immediate surgery.
Researchers analyzed more than 1,500 blood samples, looking at ctDNA levels after treatment and during follow-up to determine whether the blood test could predict whose cancer would return.
ctDNA Outperformed Clinical Response
One of the study’s most important findings was that how a patient looked clinically did not always match what the blood test showed.
Many patients appeared to have responded extremely well to treatment based on MRI scans and endoscopy. Yet some of those same patients still had detectable ctDNA in their bloodstream. Those patients were much more likely to experience a recurrence.
In other words, the blood test revealed evidence of remaining cancer that traditional imaging could not see.
What Happened to Patients Who Chose to Watch and Wait?
The results were especially striking among patients who avoided immediate surgery.
Researchers found that nearly every patient whose ctDNA remained detectable after treatment eventually developed recurrent cancer. By comparison, only a small percentage of patients whose ctDNA was undetectable experienced a recurrence during the study period.
Just as importantly, researchers found that ctDNA predicted recurrence better than clinical response alone. Even patients who appeared to have a complete or near-complete response on imaging had a significantly higher risk of recurrence if ctDNA remained positive.
This suggests ctDNA could eventually help doctors identify which patients are good candidates for watch-and-wait and which patients may benefit from additional treatment or surgery instead.
ctDNA Was Also Powerful After Surgery
The blood test remained highly predictive after surgery.
Patients whose ctDNA was still detectable several weeks after their operation had a dramatically higher likelihood of their cancer returning than patients whose ctDNA was no longer detectable.
Researchers also found that when ctDNA became positive during routine monitoring, it often did so months before cancer recurrence was diagnosed through standard clinical evaluations.
Earlier detection could eventually give doctors more time to evaluate treatment options before recurrent disease becomes more advanced.
What Could This Mean for Patients?
Although ctDNA testing is still being studied, the results point toward a future in which follow-up care is more personalized. Rather than treating every patient the same after therapy, doctors may eventually use ctDNA results to estimate an individual’s risk of recurrence.
Patients with no detectable ctDNA might be able to avoid unnecessary testing or treatment if future studies confirm these findings. Meanwhile, patients with persistent ctDNA could benefit from closer surveillance, additional imaging, enrollment in clinical trials, or other treatment strategies designed to eliminate remaining cancer cells.
Researchers stress that these decisions cannot yet be based on ctDNA alone, but the test may become an important part of the overall picture.
What Are the Study’s Limitations?
While the findings are encouraging, this was a retrospective study, meaning researchers looked back at patients who had already received treatment rather than conducting a randomized clinical trial.
Patients were treated at multiple institutions, the timing of ctDNA testing varied, and doctors made treatment decisions according to routine clinical practice rather than a standardized study protocol. Follow-up was also relatively short for some patients.
Because of these limitations, larger prospective clinical trials are needed before ctDNA testing can routinely guide decisions about surgery, surveillance, or additional treatment.
Key Takeaway
For years, doctors have relied primarily on scans and physical examinations to determine whether rectal cancer treatment has been successful. This study suggests that ctDNA may help identify patients at higher risk of recurrence, support decisions about watch-and-wait management, and guide follow-up care after treatment.
While more research is needed before ctDNA becomes part of standard practice for every patient with rectal cancer, these findings add to growing evidence that a simple blood test could play an increasingly important role in personalized cancer care.
Reference
Chakrabarti S, Cohen SA, Tin A, et al. Utility of Circulating Tumor DNA to Assess Tumor Response in Patients with Locally Advanced Rectal Cancer Undergoing Neoadjuvant Therapy. Cancers. 2026;18:589.
