Myriad Genetics announced that The Lancet Oncology published a study demonstrating the performance of its molecular residual disease (MRD) test, Precise MRD, in patients with oligometastatic clear-cell renal cell carcinoma (ccRCC). The study showed that circulating tumor DNA (ctDNA) levels were associated with patients' response to metastasis-directed radiation therapy (MDT), potentially enabling treatment de-escalation for select patients.
Clinical Performance and Key Findings
The Phase 2 trial revealed significant clinical insights about the ultrasensitive MRD testing approach. Notably, 94% of patients tested at baseline had ctDNA levels below 100 parts per million (ppm), falling within the ultrasensitive testing range. This finding is particularly significant given that renal cancer is known to have low tumor fraction, making ctDNA detection challenging for first-generation MRD assays.
The study demonstrated a clear correlation between ctDNA status and treatment outcomes. Patients who tested positive with Precise MRD prior to metastasis-directed radiotherapy without systemic therapy (MRWS) progressed to systemic therapy within a median time of 27 months. In contrast, those who tested negative were maintained on MDT for a median time of 54 months—nearly double the duration.
"Median systemic therapy-free survival was nearly double in those who were ctDNA negative compared to those who were ctDNA positive, suggesting that ctDNA may be a promising biomarker to identify those who will benefit most from MDT," said Chad Tang, MD, associate professor in the department of genitourinary radiation oncology at The University of Texas MD Anderson Cancer Center and principal investigator of the study.
Survival Outcomes and Treatment Implications
The survival data provided encouraging results for patients who could avoid systemic therapy. In those who were ctDNA negative and maintained on MDT, overall survival was not compromised, with survival rates of 94% at two years and 87% at three years. This finding suggests that carefully selected patients can delay or potentially avoid systemic treatments while maintaining favorable outcomes.
"Our study demonstrated that MDT successfully delayed the initiation of systemic therapy in patients with oligometastatic ccRCC," Tang noted. The ability to identify patients who can safely defer systemic therapy represents a significant advancement in personalized cancer care, potentially sparing patients from serious side effects associated with systemic treatments.
Technical Capabilities and Future Applications
Dale Muzzey, PhD, chief scientific officer at Myriad Genetics, emphasized the technical achievement of the Precise MRD test in this challenging clinical setting. "Using the ultrasensitive Precise MRD Test, we could detect a wide range of ctDNA levels – from very high to very low – that were associated with response to metastasis-driven therapy," Muzzey explained.
The Precise MRD Test utilizes tumor-informed, whole genome sequencing (WGS) technology to monitor hundreds to thousands of tumor-specific variants, enabling exceptional sensitivity and quantification of ctDNA in cancer patients' blood. This comprehensive approach allows for monitoring throughout a patient's clinical care, from immediately after diagnosis through treatment.
Study Design and Significance
The study, titled "Phase 2 trial of metastasis directed radiotherapy without systemic therapy (MRWS) for oligometastatic clear cell renal cell carcinoma (ccRCC) and investigation of circulating tumor DNA (ctDNA) as a personalized biomarker," was initially presented at the 2025 American Association for Cancer Research Annual Meeting. The investigator-initiated single-arm trial enrolled patients with ccRCC and up to 5 metastases (NCT03575611).
This research represents one of the largest trials conducted to date in this clinical setting and includes one of the longest follow-up periods evaluating sequential metastasis-directed therapy without systemic therapy for ccRCC. The Precise MRD Test was incorporated as part of an exploratory endpoint to determine the association of translational biomarkers with patient outcomes.
The successful performance of Precise MRD in renal cancer, where biomarkers are urgently needed to inform care decisions, may indicate its potential utility across other cancer types. As Muzzey noted, "The performance of Precise MRD in this challenging clinical setting is an encouraging indicator of its sensitivity in a range of other indications, such as breast cancer."
