Findings from a new study of a urine-based biomarker test suggest that it may aid in detecting kidney cancer recurrence and reduce imaging. The findings, which stem from the AURORAX-0087A trial, suggest that measuring glycosaminoglycans (GAGs) in urine samples and thereby providing a GAGome score could serve as a highly sensitive tool for monitoring minimal residual disease in patients with clear cell renal cell carcinoma (ccRCC).
The study, presented at the European Association of Urology (EAU) Congress in Madrid, was designed to address a significant clinical challenge: how to effectively monitor kidney cancer patients for recurrence without excessive reliance on imaging. The trial was undertaken to prove the validity of the GAGome test. “For any diagnostic test to even be considered for major guidelines, it needs to be prospectively developed and externally validated,” explained lead study researcher, Saeed Dabestani, associate professor at Lund University and a member of the European Association of Urology’s kidney cancer guidelines panel.
The GAGome score
This study’s foundation is that glycosaminoglycans, long unbranched polysaccharides found in the extracellular matrix and on cell surfaces, may have distinct profiles in cancerous versus noncancerous states. “It has already been established that GAGs play a crucial role in cell signaling, tumor microenvironment integrity, and immune evasion,” Dabestani noted.
The trial was designed in two phases, with the first cohort, included in the current study, aimed at calibrating the newly developed GAGome score. This mathematical model assigns a probability score (ranging from 0 to 100) based on specific GAG profiles in urine samples. The study enrolled 134 patients who were followed for up to 18 months. The second phase is currently underway and is designed to validate these findings in a new patient population externally.
The study’s initial cohort involved 134 patients treated at 23 hospitals across the U.K., EU, U.S., and Canada. The patients were all diagnosed with ccRCC which had not spread beyond the kidney, and which was treated with surgery. Most had their kidney wholly removed. All patients continued to have CT scans as standard monitoring after surgery, alongside a urine test every three months. Each urine sample was analyzed using mass spectrometry to produce a score out of 100, the GAGome score. A score above 12 is considered a positive.
High sensitivity but moderate specificity
The results from this study demonstrated that the GAGome test had a sensitivity of 90% and a specificity of 51% for detecting recurrence in kidney cancer patients. More notably, the test exhibited a negative predictive value of 97%, meaning that a negative result strongly indicates the absence of recurrent disease. However, the positive predictive value was 26%, suggesting that while the test is highly effective at ruling out recurrence, a positive result may still require confirmation through imaging.
“If the test is negative, you have a high chance of ruling out any cancer using a urine-based biomarker,” Dabestani explained. “But because imaging was the reference standard, we can’t yet conclude that it is better than radiological methods in detecting recurrence.”
Potential to reduce “scanxiety” and overtreatment
Around one-fifth of ccRCC patients who have surgery to remove their cancer will see it return within five years—the majority within the first two years. Currently, the only way to monitor patients is through a scan—usually a CT scan—every 6 to 12 months, with the frequency depending on their level of risk.
Dabestani noted that one of the significant implications of this test is its potential to reduce the number of imaging scans for kidney cancer patients, a common issue in follow-up care. “We found that some patients receive twice as many scans as recommended, while others receive half as many, with no clear survival benefit from the increased frequency,” said Dabestani. He noted that overuse of imaging can contribute to patient anxiety (often referred to as “scanxiety”) and healthcare system burdens.
“What we are hoping to achieve is a more individualized approach to follow-up,” he stated. “If a patient has a negative GAGome score, they may not need immediate imaging, thus reducing unnecessary radiation exposure and anxiety.”
Next steps: Validation and regulatory approval
The second phase of the AURORAX-0087 trial is expected to conclude by the end of April 2025. This phase will replicate the study design in a separate group of patients to ensure the robustness of the findings.
Regarding the broader impact, the study highlights the increasing interest in utilizing non-invasive biomarkers for cancer monitoring. “To our knowledge, GAGome profiling is not currently in clinical use for any cancer,” Dabestani said. “This research could pave the way for a new category of diagnostic tools that improve patient care while optimizing healthcare resources.”
If further validated and with regulatory approval, the GAGome test could offer a shift in kidney cancer management—reducing the need for excessive and expensive imaging while providing a reliable method to monitor for recurrence.
