Blood Test Guides Post-Surgical Immunotherapy for Muscle-Invasive Bladder Cancer

Now, a new international phase 3 study has demonstrated that a simple blood test detecting circulating tumor DNA (ctDNA) can accurately identify which patients are most likely to benefit from immunotherapy. The findings, published in The New England Journal of Medicine, suggest a precision medicine approach—where treatment is guided by ctDNA results—can improve survival outcomes while sparing others from unnecessary therapy.

In the global, randomized IMvigor011 trial co-led by Dana-Farber Cancer Institute (Boston, MA, USA), Technical University of Munich (Munich, Germany), and Queen Mary University of London (London, UK), more than 800 patients who showed no clinical signs of cancer after surgery were screened for ctDNA every six weeks for up to one year. A total of 250 patients who tested ctDNA-positive—indicating minimal residual disease—were randomized in a 2:1 ratio to receive either atezolizumab, an immune checkpoint inhibitor targeting PD-L1, or a placebo. Patients who remained ctDNA-negative received no additional treatment.

The results were striking: patients who tested ctDNA-positive and received atezolizumab had a 36% lower risk of cancer recurrence compared to those receiving a placebo, and a 41% reduction in risk of death. This benefit was seen both in patients who were ctDNA-positive immediately after surgery and those who became positive later during follow-up.

In contrast, ctDNA-negative patients remained largely cancer-free, with 89% disease-free survival and over 90% overall survival at a median follow-up of 21.8 months—indicating they could safely forgo further therapy. The study builds on earlier research, including the IMvigor010 trial, which showed no overall benefit for atezolizumab when given to all post-surgery patients. However, retrospective data hinted that patients with ctDNA positivity—signifying lingering cancer cells undetectable by conventional scans—did derive benefit.

IMvigor011 was designed to prospectively confirm this hypothesis and is the first trial to show that adjuvant immunotherapy guided by ctDNA testing can improve both disease-free and overall survival. Importantly, no new side effects were reported, reinforcing the safety of atezolizumab in this setting. The trial’s results are expected to influence clinical practice and regulatory guidance by linking immunotherapy use to ctDNA testing.

“This is the first time that an adjuvant immunotherapy trial has shown a survival benefit in patients selected based on ctDNA testing,” said Dr. Joaquim Bellmunt, co-principal investigator of the study. “Patients who are ctDNA-positive benefit significantly from atezolizumab, while those who remain ctDNA-negative can be spared unnecessary treatment.”

Related Links:
Dana-Farber Cancer Institute
Technical University of Munich
Queen Mary University of London