Natera Receives FDA Approval for Signatera CDx as First Blood-Based MRD Companion Diagnostic in Muscle-Invasive Bladder Cancer
Natera announced that the U.S. Food and Drug Administration has approved Signatera CDx as a companion diagnostic for use alongside adjuvant atezolizumab, marketed as Tecentriq, in patients with muscle-invasive bladder cancer (MIBC).
The approval represents a major milestone in oncology and precision medicine because it marks the first companion diagnostic approval in the field of blood-based minimal residual disease, commonly referred to as MRD. Industry experts view the decision as an important step toward broader adoption of personalized, MRD-guided cancer care, where treatment decisions can increasingly be based on the detection of circulating tumor DNA rather than relying solely on imaging or traditional clinical indicators.
According to Natera, the approval allows Signatera CDx to be used to identify patients with muscle-invasive bladder cancer who are ctDNA MRD-positive following surgery and who may benefit from treatment with adjuvant atezolizumab immunotherapy.
The approval was supported by findings from the global Phase III IMvigor011 clinical trial sponsored by Genentech. Results from the study were published in The New England Journal of Medicine in October 2025 and demonstrated that patients identified as MRD-positive using Signatera experienced meaningful improvements in disease-free survival and overall survival when treated with immunotherapy.
At the same time, the study also showed that patients who remained MRD-negative achieved excellent outcomes without receiving adjuvant treatment. According to the published findings, MRD-negative patients demonstrated a two-year overall survival rate of 97% despite not receiving additional immunotherapy after surgery.
Researchers and clinicians believe these results may significantly influence future treatment strategies in bladder cancer because they suggest that MRD testing can help determine which patients are most likely to benefit from additional therapy while potentially sparing others from unnecessary treatment exposure.
Muscle-invasive bladder cancer is an aggressive form of bladder cancer that penetrates the muscle layer of the bladder wall and carries a substantial risk of recurrence even after surgical removal of the bladder, a procedure known as radical cystectomy. Historically, physicians have faced challenges in determining which patients are at highest risk for recurrence following surgery and therefore most likely to benefit from adjuvant treatment.
Traditional monitoring methods often rely on imaging studies that may only detect recurrence after significant tumor growth has already occurred. By contrast, circulating tumor DNA technologies such as Signatera are designed to detect microscopic traces of cancer DNA in the bloodstream at much earlier stages.
Signatera is a personalized molecular residual disease assay that analyzes tumor-specific DNA mutations identified from an individual patient’s cancer tissue. The test then tracks those unique mutations in blood samples over time to detect minimal residual disease and early molecular recurrence.
According to Natera, the FDA approval validates years of research supporting the clinical utility of MRD-guided treatment strategies across multiple cancer types. The company stated that Signatera has already become widely integrated into precision oncology practice, supported by more than 185 peer-reviewed publications and Medicare coverage across several cancers, including bladder, breast, colorectal, lung, ovarian, and pan-cancer immunotherapy monitoring.
Thomas Powles, who also serves as Chair of Barts Cancer Centre at St. Bartholomew’s Hospital, described the IMvigor011 findings and FDA approval as transformative developments in cancer care.
According to Powles, the study signals a shift toward using MRD to guide not only whether patients should receive treatment, but also when therapy should begin and which individuals are most likely to benefit. He explained that clinicians have traditionally relied on imaging scans to detect recurrent disease, but by the time recurrence becomes visible on imaging, millions of cancer cells may already be present in the body.
Powles stated that Signatera enabled earlier detection of tumor DNA in the bloodstream, providing physicians with what he described as a significant head start in identifying recurrence risk and improving patient outcomes.
Patient advocacy organizations also welcomed the approval and its potential implications for treatment decision-making in bladder cancer.
Meri-Margaret Deoudes noted that the period following bladder removal surgery is often associated with uncertainty and anxiety for patients and families due to the ongoing risk of recurrence.
According to Deoudes, approaches such as Signatera can provide clinicians with additional information regarding which patients are more likely to experience disease recurrence, potentially helping guide more informed decisions regarding monitoring and treatment. She emphasized the importance of ensuring patients have access to tools that may reduce unnecessary treatment exposure while still supporting timely intervention for those who need it most.
Natera executives described the FDA decision as a defining milestone for precision oncology and personalized cancer medicine.
Solomon Moshkevich stated that the approval validates a long-term vision first introduced by the company approximately a decade ago. According to Moshkevich, the decision establishes Signatera MRD as a new standard of care in muscle-invasive bladder cancer and further reinforces the growing role of MRD-guided treatment approaches across oncology.
He also highlighted Natera’s broader clinical research efforts, including the company’s portfolio of TOMR trials and recent technological innovations involving ultrasensitive genome-based MRD detection and phased variant analysis. These technologies are intended to improve sensitivity and accuracy in detecting minimal residual disease across multiple tumor types.
The IMvigor011 trial is considered particularly important because it provides prospective evidence supporting MRD-guided care in bladder cancer. Prospective clinical validation is widely viewed as a critical requirement for integrating biomarker-driven approaches into routine oncology practice and regulatory decision-making.
Experts believe the study may help accelerate broader adoption of MRD-guided treatment strategies in additional cancers as further evidence emerges from ongoing clinical trials.
Approximately 30,000 new cases of muscle-invasive bladder cancer are diagnosed annually in the United States, with an estimated 150,000 cases diagnosed globally each year. Radical cystectomy, with or without neoadjuvant therapy, remains a standard treatment approach and can achieve long-term disease control in roughly half of patients. However, recurrence rates remain substantial, and clinicians have historically lacked precise tools to stratify recurrence risk following surgery.
The ability to identify molecular residual disease through blood testing may therefore offer significant clinical advantages. MRD testing can potentially help physicians determine which patients require immediate adjuvant intervention while allowing lower-risk patients to avoid unnecessary treatment-related toxicity and healthcare burden.
The approval also reflects broader trends within oncology toward increasingly personalized treatment models that rely on molecular biomarkers, genomic profiling, and real-time disease monitoring. Rather than treating all patients uniformly, MRD-guided care seeks to tailor treatment intensity based on an individual patient’s molecular disease status.
In recent years, circulating tumor DNA technologies have gained substantial attention for their potential applications in early cancer detection, recurrence monitoring, treatment selection, and response assessment. However, this FDA approval represents one of the most significant regulatory milestones yet achieved in the field.
With the approval of Signatera CDx for use alongside atezolizumab in muscle-invasive bladder cancer, Natera believes the oncology field is entering a new era where blood-based MRD testing may increasingly influence treatment decisions and clinical management strategies.
Looking ahead, the company plans to continue expanding research efforts evaluating Signatera across additional tumor types and therapeutic settings. As more clinical evidence accumulates, MRD-guided precision oncology may become an increasingly central component of cancer treatment, helping clinicians deliver more individualized care while improving outcomes and reducing overtreatment for patients worldwide.
About Natera
Natera™ is a global leader in cell-free DNA and precision medicine, dedicated to oncology, women’s health, and organ health. We aim to make personalized genetic testing and diagnostics part of the standard-of-care to protect health and inform earlier, more targeted interventions that help lead to longer, healthier lives.
Natera’s tests are supported by more than 350 peer-reviewed publications that demonstrate excellent performance. Natera operates ISO 13485-certified and CAP-accredited laboratories certified under the Clinical Laboratory Improvement Amendments (CLIA) in Austin, Texas, and San Carlos, California, and through Foresight Diagnostics, its subsidiary, operates an ISO 27001-certified and CAP-accredited laboratory certified under CLIA in Boulder, Colorado.
