ctDNA Positivity May Improve Post-Surgical Immunotherapy Response in Bladder Cancer

Circulating tumor DNA (ctDNA) may help predict outcomes in patients with high-risk urothelial cancer, according to research published in the journal Nature.

The research showed that patients whose cancer was ctDNA-positive and had molecular residual disease (MRD) relapse tended to have better outcomes with post-surgical Tecentriq (atezolizumab).

“These data suggest that adjuvant (Tecentriq) atezolizumab may be associated with improved outcomes compared with observation in patients who are positive for ctDNA and who are at a high risk of relapse,” the study authors wrote. “These findings, if validated in other settings, would shift approaches to postoperative cancer care.”

The researchers evaluated outcomes from a randomized phase 3 trial, IMvigor010, which compared Tecentriq to observation after surgical resection for operable urothelial cancer. They analyzed data of 581 post-surgery patients who were evaluable for ctDNA.

“ctDNA can overcome shortcomings of tissue-based biomarkers, including access to tissue, use of archival samples and tumor heterogeneity, and as a result, is increasingly used to guide treatment decisions,” the authors explained in the article.

Out of the 581 patients, 214 were positive for ctDNA, which identified patients at a higher risk of disease recurrence than though whose disease was ctDNA negative. Within the positive population, 116 patients received Tecentriq and 98 were in the observation group.

The patients who were ctDNA-positive had improved disease-free survival (DFS) and overall survival (OS) with adjuvant Tecentriq as opposed to patients undergoing observation. There was no notable difference in DFS between groups for the patients who were ctDNA-negative.

After the third cycle (six weeks of randomization), 18.2% of the patients who were ctDNA-positive at the beginning of cycle one and received Tecentriq became ctDNA-negative. These patients also had better DFS and OS than those who remained positive in the Tecentriq group.

The researchers also analyzed ctDNA data from another phase 2 study (ABACUS) of Tecentriq before cystectomy in muscle-invasive urothelial cancer to support their findings. Out of 40 patients, 62.5% were positive for ctDNA. Tecentriq was associated with reduced ctDNA levels in patients who had a response to neoadjuvant therapy. Patients who did not respond to therapy did not have significantly changed ctDNA levels.

Taken together, the findings showed improved outcomes in patients who were positive for ctDNA that received Tecentriq.

“ctDNA status was a prospective but exploratory end point, and therefore further studies are required to validate and expand its clinical utility,” the authors wrote.

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