A groundbreaking clinical study shows that Signatera, a personalized blood test that detects microscopic traces of cancer DNA, can help doctors more precisely decide which bladder cancer patients benefit most from additional treatment after surgery.
The phase 3 IMvigor011 trial, presented during the prestigious Presidential Symposium at the 2025 European Society for Medical Oncology (ESMO) Congress, found that Signatera-guided immunotherapy led to significantly better survival for patients with muscle-invasive bladder cancer (MIBC).
Study Overview
Bladder cancer is the sixth most common cancer in the United States. About one in four newly diagnosed cases involves muscle-invasive disease—a more aggressive form that requires surgical removal of the bladder (cystectomy).
While surgery can cure many patients, it has been very difficult to identify who is most at risk of their cancer returning. The IMvigor011 trial, sponsored by Genentech (a member of the Roche Group) and conducted in collaboration with Natera, Inc., set out to solve this problem using Signatera’s circulating tumor DNA (ctDNA) testing.
How the Trial Worked
- A total of 761 patients were monitored after surgery using Signatera testing—performed up to seven times during the first year.
- Half of the patients eventually tested positive for ctDNA (indicating possible remaining cancer cells).
- Those who tested positive were randomly assigned to receive either atezolizumab (Tecentriq) or a placebo.
Results showed that:
- Patients who tested Signatera-positive and received atezolizumab had more than double the median disease-free survival (DFS) compared to those who received placebo (9.9 months vs. 4.8 months).
- Median overall survival (OS) improved by 41%—32.8 months with atezolizumab compared to 21.1 months with placebo.
- Patients who remained Signatera-negative throughout follow-up had excellent outcomes without any additional therapy, with 95% disease-free survival at one year.
What This Means for Patients
According to Professor Thomas Powles, lead investigator of the IMvigor011 study and Director of the Barts Cancer Centre in London, these findings are “practice-changing.” Patients who tested Signatera-positive clearly benefitted from atezolizumab, while those with persistently negative results avoided unnecessary treatment and side effects.
Dr. Alexey Aleshin, Chief Medical Officer at Natera, added that this is the first study to show doctors can safely extend the window for post-surgery decisions to one year, allowing treatment to begin only when ctDNA testing shows signs of recurrence.
What Is ctDNA?
Circulating tumor DNA (ctDNA) refers to small fragments of DNA shed by cancer cells into the bloodstream. These fragments carry the same genetic mutations found in the patient’s tumor.
A ctDNA blood test, like Signatera, analyzes a patient’s blood to detect these tumor-specific traces even when imaging scans show no visible cancer. Detecting ctDNA early can:
- Identify microscopic disease long before symptoms or imaging changes appear.
- Help doctors determine who truly needs additional treatment after surgery.
- Allow patients with no detectable ctDNA to avoid unnecessary chemotherapy or immunotherapy, reducing side effects and improving quality of life.
This form of testing is a key advance in personalized oncology, giving patients a more targeted, precise, and data-driven approach to follow-up care.
Moving Toward a New Standard of Care
The success of IMvigor011 supports Natera’s plan to seek FDA approval of Signatera as a companion diagnostic tool to help guide post-surgery immunotherapy decisions in MIBC.
If approved, this approach could spare many patients from overtreatment while ensuring early and effective care for those most at risk of recurrence. Experts believe this study could redefine how bladder cancer—and potentially other cancers—are managed after surgery.
References
- National Comprehensive Cancer Network, Bladder Cancer. NCCN Clinical practice guidelines in oncology (NCCN Guidelines). Version 4.2021.
- Gakis G. Management of Muscle-invasive Bladder Cancer in the 2020s: Challenges and Perspectives. Eur. Urol. Focus. 2020;6(4):632-638.
- Stein JP, Lieskovsky G, Cote R, et al. Radical cystectomy in the treatment of invasive bladder cancer: long-term results in 1,054 patients. J Clin Oncol. 2001;19(3):666–675. doi:10.1200/JCO.2001.19.3.666
- Yafi FA, Aprikian AG, Chin JL, et al. Contemporary outcomes of 2,287 patients with bladder cancer treated with radical cystectomy: a Canadian multicentre experience. BJU Int. 2011;108(4):539–545. doi:10.1111/j.1464-410X.2010.09912.x
