Signatera Guides Bladder Cancer Treatment After Surgery

Dr. Minetta Liu, a medical oncologist and chief medical officer for Natera Oncology and Early Cancer Detection, explains how Signatera is changing bladder cancer care. Signatera is a personalized blood test that detects tiny fragments of tumor DNA in the bloodstream, identifying molecular residual disease even when cancer isn’t visible on scans or exams.

In the IMvigor010 trial, Signatera guided treatment after bladder surgery. Patients who tested positive for ctDNA received immunotherapy with Tecentriq (atezolizumab), doubling disease-free survival and improving overall survival by 41% versus placebo. Those who remained ctDNA-negative had excellent outcomes. Regular testing lets doctors detect recurrence early and make timely treatment decisions, giving patients a clearer path for post-surgery care.

CURE: For patients who may be hearing about this for the first time, what is Signatera and how does it help detect bladder cancer returning after surgery?

Liu: So Signatera is a blood test, and it's a blood test that picks up tiny fragments of tumor-related material or DNA in the bloodstream. It is a personalized test. We develop a fingerprint, basically, for every tumor and every individual patient. This is the true way that we can personalize care for patients. It's looking at what we call molecular residual disease. Again, it's a fingerprint. It's not giving you guidance on what treatment to give exactly, like targeted therapies. There are other blood tests out there, but this is really the most reliable and sensitive way we have of detecting residual cancer, even if you can't see that cancer clinically — meaning you can't find it on physical exam or see it on imaging.

Can you explain what the IMvigor010 trial set out to learn, and why these results are considered a major step forward in bladder cancer care?

We're very excited by these landmark results from IMvigor010, which was a pharmaceutical company-sponsored trial. It's a phase 3 global study in muscle-invasive bladder cancer that aimed to prove that acting on a ctDNA result by Signatera would define the patient population with high-risk muscle-invasive bladder cancer that would benefit from the use of atezolizumab, which is immunotherapy, versus not giving it. It's a placebo-controlled trial and the first study to demonstrate that acting on a ctDNA result makes a difference in patients' lives. This is the first true demonstration of clinical utility with Signatera.

How does Signatera help identify who truly needs additional therapy and who doesn't?

Typically in bladder cancer, some patients receive systemic therapy or chemotherapy first, and then they go to surgery. Ultimately, everybody has a cystectomy or surgery, and once that's done, there's nothing to measure anymore. The question has always been: do these patients need additional medications to try to get rid of cancer cells wherever they are?

One of the additional values of Signatera is that not only is it personalized, but it can identify cancer cells whether they're from the original tumor in the bladder or if they spread to neighboring lymph nodes or elsewhere in the body. You want to find that before you can see it on a scan. We wanted to detect it at the earliest point possible.

After cystectomy, patients had Signatera blood tests at regular intervals — every six weeks for the first six months, then every 12 weeks for the second six months, up to a year after surgery. If Signatera was continuously negative, that was a strong sign the patient was doing really well, and these patients had extremely good outcomes. You need to follow the test regularly; it’s not a one-time check because things can change over time.

For patients who became ctDNA-positive by Signatera, meaning the blood test suggested cancer was lurking somewhere, they’d get a scan to ensure there was no evidence of cancer by imaging. If it was just a blood signal, they were able to get treatment. Some patients received [Tecentriq], some received placebo, but this is how we identified that using Signatera as a trigger to guide treatment benefited those patients, with a significant improvement in both disease-free and overall survival.

Speaking of that benefit, what specifically did the study find for patients who tested positive with Signatera after surgery and received immunotherapy?

Disease-free survival means the cancer didn't come back. Patients who received [Tecentriq] versus placebo had a two-fold improvement in disease-free survival: 9.9 months versus 4.8 months. Importantly and somewhat surprisingly, there was also an overall survival benefit: a 41% improvement, with 32.8 months versus 21.1 months.

How might these results change the way doctors monitor and treat bladder cancer in everyday practice?

This is a practice-changing study. Bladder cancer has never had a blood test to monitor patients. Previously, monitoring was based on factors from diagnosis, microscopic findings at surgery, and response to treatment before surgery. Now, during surveillance — which for patients and oncologists has often felt like waiting for the other shoe to drop — you have a way to identify patients at high risk of recurrence.

Serial testing lets you see if Signatera is persistently negative, suggesting the patient will do well. If it becomes positive, there’s now a treatment opportunity with [Tecentriq] that didn’t exist before. This should change the paradigm for treating muscle-invasive bladder cancer. Even as available medications evolve, stratifying patients by persistently negative or positive Signatera results can guide treatment decisions. Positive is not bad—it signals that more needs to be done.

What should patients undergoing or recovering from bladder cancer surgery know about blood-based tests like Signatera and how they might guide future treatment decisions?

I would encourage patients to talk to their providers about Signatera. There are other products out there, but they are not all created the same. This is about shared decision-making: a physician and patient discussing what’s available and how it might fit into their management plan.

Transcript has been edited for clarity and conciseness.

For more news on cancer updates, research and education, don’t forget to subscribe to CURE®’s newsletters here.