Circulating Tumor DNA Following Surgery Predicts Bladder Cancer Recurrence

Worldwide, there were approximately 573,000 cases of bladder cancer with about 212,000 deaths in 2020. Surgery, which is the usual first treatment for the disorder, often leaves behind some cancer cells, molecular residual disease (MRD), which can regenerate the tumor. Rather than just waiting to see if the cancer returns following surgery, researchers are developing minimally invasive approaches for detection of MRD after surgery to identify patients who are at risk for metastatic relapse.

In this regard, circulating tumor DNA (ctDNA) holds promise as a biomarker for molecular residual disease and relapse. This follows from studies showing that liquid biopsy analysis of circulating cell-free DNA (cfDNA) from peripheral blood could be a valuable diagnostic tool in oncology, since sample collection is quick and minimally invasive. In cancer patients, cfDNA consists in part of cancer-derived circulating tumor DNA (ctDNA), and it has been shown that tumor-related genetic and epigenetic alterations can be detected by analyzing cfDNA in cancer patients. As a consequence, cfDNA analysis holds great promise for precision oncology and personalized therapies, and is currently being evaluated in a broad range of clinical studies.

To test for MRD in bladder cancer patients following surgery, investigators at Queen Mary University of London (United Kingdom) used a ctDNA liquid biopsy approach to evaluate treatment outcomes in 581 individuals who were enrolled in a randomized phase III trial and a phase II study, which investigated whether the drug atezolizumab could reduce cancer recurrence in high-risk muscle-invasive urothelial carcinoma.

Atezolizumab is a fully humanized, engineered monoclonal antibody of IgG1 isotype against the protein programmed cell death-ligand 1 (PD-L1). It is used to treat urothelial carcinoma, non-small cell lung cancer (NSCLC), triple-negative breast cancer (TNBC), small cell lung cancer (SCLC), and hepatocellular carcinoma (HCC). The drug’s most common adverse side effects include urinary tract infection, fatigue, decreased appetite, nausea, and infections.

Results obtained by this study revealed that patients with ctDNA-positive blood tests after surgery were at higher risk of cancer recurrence than those who were ctDNA-negative. Treatment with atezolizumab did not significantly improve disease-free survival (DFS) or overall survival (OS) in the whole study population; however, in the ctDNA-positive subgroup of patients evaluated in this study, treatment with atezolizumab compared with observation alone significantly improved DFS and OS. The outcomes in patients who were ctDNA-negative did not appear to differ whether they received atezolizumab or not.

First author Dr. Tom Powles, professor of genitourinary oncology at Queen Mary University of London, said, "These novel findings demonstrate ctDNA as a marker for residual disease and response to atezolizumab. We also found ctDNA measurement to be more accurate than traditional radiology at identifying disease relapse. These findings may change our understanding of post-surgical cancer care and, if validated in this setting as well as across tumor types, they may also change clinical practice."

The study was published in the June 16, 2021, online edition of the journal Nature.

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Queen Mary University of London