Patients with bladder cancer who still have cancer remaining after surgery are known to be at the highest risk of the disease coming back. In contrast, patients without residual disease are less likely to benefit from additional treatment. A test that can accurately detect minimal residual disease (MRD) and predict who will benefit from more therapy can help many patients avoid unnecessary chemotherapy and its side effects.
Muscle invasive bladder cancer (MIBC) carries a substantial risk of recurrence and death: nearly half of patients have their cancer return within two years of cystectomy, the surgery to remove the bladder. Patients with muscle invasive urothelial (bladder) cancer who have evidence of circulating tumor DNA (ctDNA) after surgery are at especially high risk, because this blood test shows that microscopic cancer remains in the body even when scans look clear. Earlier research, including the IMvigor010 trial, showed that these high‑risk patients can have better outcomes when treated with adjuvant Tecentriq (atezolizumab) immunotherapy rather than just being observed after surgery.
Recently, the U.S. Food and Drug Administration (FDA) approved atezolizumab (Tecentriq) and atezolizumab and hyaluronidase‑tqjs (Tecentriq Hybreza) as adjuvant treatments for adults with MIBC after cystectomy who have ctDNA‑defined MRD, as determined by an FDA‑authorized test. At the same time, the FDA approved Signatera CDx as a companion diagnostic to identify which patients have ctDNA MRD and are candidates for treatment with Tecentriq or Tecentriq Hybreza. This means the ctDNA test and the immunotherapy are now formally linked in a personalized treatment approach for this group of patients.
MRD assessment using personalized ctDNA testing is transforming care for MIBC by guiding immunotherapy decisions after surgery. In the phase III IMvigor011 trial, patients who tested positive with Signatera after cystectomy (showing MRD) had significantly better disease‑free and overall survival when treated with atezolizumab compared with placebo. In contrast, patients who consistently tested Signatera‑negative had excellent outcomes without receiving additional adjuvant therapy.
How MRD Assessment Personalizes Care
Measuring MRD via ctDNA allows doctors to more precisely estimate a patient’s risk of bladder cancer coming back after surgery. While about half of all MIBC patients will experience recurrence within two years of cystectomy, ctDNA MRD testing helps distinguish those who truly need further immunotherapy from those who can safely avoid it.
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Patients who are Signatera‑positive (detectable ctDNA MRD after surgery) benefit from adjuvant Tecentriq, with longer disease‑free and overall survival compared with observation alone.
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Patients who are Signatera‑negative (no detectable MRD) often have excellent outcomes without immunotherapy, with reported survival rates of 100% at 12 months and 98% at 18 months in preliminary analyses, allowing them to be closely monitored without added treatment.
Latest Clinical Evidence
IMvigor011 is the first prospective, phase III study in MIBC to use personalized ctDNA‑guided MRD surveillance and randomization to treatment. After surgery, patients were monitored for up to 12 months with serial ctDNA testing. Those who became ctDNA‑positive without visible recurrence on imaging were randomized to receive atezolizumab or placebo, while Signatera‑negative patients continued standard follow‑up with imaging and additional ctDNA tests. Results from IMvigor011, along with earlier IMvigor010 data, contributed to the evidence base supporting MRD‑guided use of Tecentriq and helped inform the FDA’s decision to approve atezolizumab and Signatera CDx in this setting.
What This Means for Patients
These advances are moving bladder cancer care toward more personalized treatment. Patients who do not show molecular evidence of recurrence on ctDNA testing may be able to avoid unnecessary chemotherapy or immunotherapy, reducing side effects and costs, while those with detectable MRD can receive adjuvant Tecentriq to lower their risk of the cancer returning and improve survival. Ongoing research and real‑world experience are continuing to strengthen confidence in ctDNA MRD testing as a companion diagnostic tool and in MRD‑guided immunotherapy as a new standard of care for high‑risk muscle invasive bladder cancer.
References:
- Powles T, Assaf ZJ, Davarpanah N, et al. Clinical outcomes in post-operative ctDNA-positive muscle-invasive urothelial carcinoma (MIUC) patients after atezolizumab adjuvant therapy. ESMO Immuno-Oncology Virtual Congress 2020
- SURVIVAL ACCORDING CIRCULATING TUMOUR DNA STATUS IN THE STUDY OF ADJUVANT ATEZOLIZUMAB FOR HIGH-RISK MUSCLE INVASIVE UROTHELIAL CANCER
- https://www.nature.com/articles/s41586-021-03642-9
- DOI: 10.1200/JCO.18.02052 Journal of Clinical Oncology 37, no. 18 (June 20, 2019) 1547-1557.
- Natera announces positive surveillance analysis from the randomized phase III IMvigor011 trial in muscle-invasive bladder cancer. News release. Natera, Inc. April 5, 2024. Accessed April 8, 2024. https://tinyurl.com/3t5td7vf
- Powles T, Assaf ZJ, Davarpanah N, et al. ctDNA guiding adjuvant immunotherapy in urothelial carcinoma. Nature. 2021;595:432-437. doi:10.1038/s41586-021-03642-9
- A study of atezolizumab versus placebo as adjuvant therapy in patients with high-risk muscle-invasive bladder cancer who are ctDNA positive following cystectomy (IMvigor011). ClinicalTrials.gov. Accessed April 8, 2024. https://tinyurl.com/3r77ebjp
