Patient with bladder cancer with residual cancer following surgery are known to be at the highest risk of recurrence, and patients without residual disease are less likely to benefit from additional treatment. A test that could accurately identify the presence of minimal residual disease (MRD) and predict which patients benefit from additional treatment could help patients avoid unnecessary chemotherapy and be of great value.
Muscle invasive bladder cancer carries a substantial risk of recurrence and/or death because nearly 50 percent of patients develop recurrence within two years of cystectomy (the surgery to remove the bladder). Patients with muscle invasive urothelial (bladder) cancer and evidence of circulating cancer cell DNA (ctDNA) following surgical removal of visible cancer are known to have high risk of disease recurrence following cystectomy. However, these patients experience improved clinical outcomes when treated with adjuvant Tecentriq (atezolizumab) immunotherapy when compared to patients undergoing observation, according to results from the IMvigor010 clinical trial.1,2
MRD assessment using personalized circulating tumor DNA (ctDNA) testing is transforming treatment for muscle invasive bladder cancer (MIBC) by guiding immunotherapy decisions after surgery. The latest phase III IMvigor011 trial demonstrated that Signatera-positive patients, identified as having MRD after cystectomy, have statistically significant improvements in both disease-free and overall survival if treated with atezolizumab (Tecentriq) compared to placebo. Meanwhile, patients who consistently tested Signatera-negative experienced excellent outcomes without needing additional adjuvant therapy.
How MRD Assessment Personalizes Care
Measuring MRD via ctDNA enables precise risk stratification for bladder cancer recurrence following cystectomy. About half of all MIBC patients experience recurrence within two years of surgery, but ctDNA MRD testing can differentiate between those needing further immunotherapy and those who can be spared unnecessary treatment.
- Signatera-positive patients (with detectable ctDNA MRD post-surgery) benefit significantly from adjuvant Tecentriq, with longer disease-free and overall survival compared to observation alone.
- Signatera-negative patients (no detectable MRD) can often safely avoid immunotherapy—results show 100% survival at 12 months and 98% at 18 months, allowing for close monitoring without added therapy.
Latest Clinical Evidence
IMvigor011 is the first prospective, phase III study in MIBC using personalized ctDNA-guided MRD surveillance and treatment randomization. Patients were followed for up to 12 months after surgery; those with positive ctDNA MRD and no imaging evidence of recurrence received atezolizumab or placebo, while Signatera-negative individuals were monitored with imaging and further ctDNA testing. The results will be presented at an upcoming medical conference and a preliminary analysis of Signatera-negative patients from IMvigor011 was presented at the European Association of Urology in April 2024.
Implications for Patients
These advances mean patients may avoid unnecessary chemotherapy and immunotherapy if they do not show molecular evidence of recurrence, reducing side effects and treatment costs. The future of bladder cancer care is increasingly personalized: ongoing studies, including IMvigor011 and earlier IMvigor010 trials, have influenced Medicare coverage decisions and boosted confidence in ctDNA MRD as a companion diagnostic tool.
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
