Signatera May Predict Recurrence in Anal, Rectal Cancers

New research suggests that a personalized blood test may help patients with anal and rectal cancers better understand their risk of recurrence and guide treatment decisions, according to a news release from Natera, Inc. Findings from two recent studies highlight the clinical utility of Signatera, a circulating tumor DNA (ctDNA) test designed to detect minimal residual disease (small amounts of cancer that can remain after treatment).

Across both studies, Signatera testing was able to identify patients at higher risk of relapse and provide early signals of cancer recurrence, often before it could be detected through imaging or symptoms. These insights may help doctors tailor treatment strategies, including whether to pursue surgery or adopt a non-operative approach, and determine how closely patients should be monitored after therapy.

How Signatera testing helps predict cancer recurrence

The studies demonstrated that Signatera status (whether ctDNA is detected in the blood) is strongly associated with patient outcomes in both anal and rectal cancers.

In a study of patients with anal squamous cell carcinoma, those who tested negative for ctDNA at baseline or cleared ctDNA during treatment experienced excellent outcomes, including a 100% one-year overall survival rate and no local recurrence. In contrast, patients who remained ctDNA-positive after treatment had significantly worse outcomes, with lower survival rates and higher rates of disease progression.

Importantly, the test detected recurrence earlier than standard methods. In all patients whose cancer returned, ctDNA positivity appeared before clinical or radiographic evidence of recurrence, suggesting that Signatera could serve as an early warning system.

In rectal cancer, Signatera also helped identify patients at high risk of relapse after initial therapy. Patients who were ctDNA-positive after treatment were significantly more likely to experience tumor regrowth and require surgery, even if they initially showed a strong response.

Understanding ctDNA testing in anal and rectal cancers

ctDNA tests like Signatera analyze small fragments of tumor DNA that are shed into the bloodstream. Because the test is personalized to each patient’s tumor, it can detect even very low levels of cancer that may not be visible on imaging scans.

This type of testing is increasingly being studied in gastrointestinal cancers as a way to guide treatment decisions and improve surveillance strategies. Detecting molecular residual disease can help identify patients who may benefit from additional therapy or closer monitoring, as well as those who may safely avoid more aggressive treatment.

For patients with rectal cancer, especially those undergoing neoadjuvant therapy (treatment given before surgery), there is growing interest in non-operative management — sometimes referred to as a “watch-and-wait” approach. In this setting, tools like ctDNA testing may help determine which patients can safely delay or avoid surgery.

Study design, methods and patient population

The findings come from two separate peer-reviewed studies evaluating Signatera in distinct patient populations.

The first study, published in Nature Communications, included 84 patients with anal squamous cell carcinoma. Researchers used serial Signatera testing throughout treatment to assess how ctDNA levels changed over time and how those changes correlated with outcomes.

The second study, published in Cancers, evaluated 220 patients with locally advanced rectal cancer. All patients received neoadjuvant therapy, after which some underwent surgery and others were managed without surgery. Among these patients, 72 received non-operative management and 148 underwent surgical resection.

Researchers examined how ctDNA status after treatment could help guide decisions regarding surgery and surveillance, as well as predict long-term outcomes.

Additional findings and future implications

Beyond predicting recurrence, the studies revealed several additional insights that may influence future cancer care. In rectal cancer, patients who were ctDNA-positive and managed without surgery had approximately 4.6 times higher risk of tumor regrowth requiring surgical intervention compared with those who were ctDNA-negative.

Additionally, patients who tested negative for ctDNA after surgery experienced significantly lower relapse rates at approximately 11.5% compared with 88% among those who remained ctDNA-positive.

These findings suggest that Signatera testing could play a key role in personalizing treatment and follow-up care. For example, patients with negative ctDNA results may be able to avoid unnecessary treatments or invasive procedures, whereas those with positive results could receive earlier intervention.

Although more research is needed, these results add to growing evidence that ctDNA testing may help refine how clinicians monitor disease and make treatment decisions.

Editor's note: This article is for informational purposes only and is not a substitute for professional medical advice, as your own experience will be unique. Use this article to guide discussions with your oncologist. Content was generated with AI, reviewed by a human editor, but not independently verified by a medical professional.

References

1. “Two Publications Highlight Clinical Utility of Signatera™ in Anal and Rectal Cancers,” by Natera, Inc. News release; March 16, 2026.

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