MRD Test Detects Early Disease Recurrence in Radiation-Treated Muscle-Invasive Bladder Cancer

Muscle-invasive bladder cancer (MIBC) accounts for about one-quarter of bladder cancer cases in the U.S. and typically requires aggressive treatment. While bladder-sparing treatment options are becoming more available, there is a need to find therapeutic approaches that balance clinical effectiveness with patient quality of life. Now, a randomized study aims to reduce treatment burden for patients and utilizes a molecular residual disease (MRD) test to monitor for disease recurrence.

The ARCHER (NRG-GU015) trial has enrolled patients from over 100 sites in the U.S. and Canada, and integrates Signatera, a personalized MRD test developed by Natera (Austin, TX, USA), as a pre-specified secondary endpoint. This custom-built assay, based on the unique mutation signature of each patient’s tumor, identifies and tracks tumor mutations at the source. Once a personalized assay is designed, a patient’s blood can be used to accurately monitor for the presence or absence of the disease over time.

Image: Real-time monitoring ctDNA is a powerful tool to assess the absence or presence of MRD (Photo courtesy of Natera)

Signatera has been clinically validated in MIBC to detect recurrence months before imaging and independently predict recurrence risk following curative-intent therapy. During the ARCHER trial, Signatera samples will be collected during treatment and follow-up, allowing real-time monitoring of circulating tumor DNA (ctDNA), which is a powerful tool that can be measured to assess the absence or presence of MRD.

The ARCHER trial will assess ctDNA clearance patterns in each treatment arm as a predictive marker of treatment response and recurrence. Urine tumor DNA will also be evaluated as an exploratory endpoint, further expanding insights into disease monitoring. The use of ctDNA dynamics in this trial reflects a shift toward refining clinical surveillance beyond imaging and cystoscopy.

Tracking molecular changes in real time could enable earlier detection of recurrence, more precise treatment strategies, and reduced reliance on invasive procedures. If successful, the trial could demonstrate how therapy intensity and duration may be safely reduced, easing patient burden while maintaining effective outcomes.

“With Signatera as a key assessment in the ARCHER trial, we aim to evaluate ctDNA dynamics to detect early molecular signs of disease recurrence in real time and refine our clinical surveillance toolbox beyond imaging and cystoscopy,” said Catherine Spina, M.D., Ph.D., co-chair of translational science for the study. “By utilizing ctDNA to monitor treatment response and recurrence, we hope to improve clinical outcomes for patients with MIBC.”

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