Urine Glycosaminoglycan Scores Show High Sensitivity to Detect ccRCC

The sensitivity and specificity of GAGome scores were consistent across subsets, with no significant interactions observed for sex, age, geographical area, or TNM stage.

Urine glycosaminoglycan profile (GAGome) scores exhibited high sensitivity to detect clear cell renal cell carcinoma (ccRCC) recurrence after surgery, according to findings from the observational diagnostic AURORAX-0087A (NCT04006405) test cohort study published in European Urology Oncology.¹

According to the results, GAGome scores correlated linearly with the probability of radiological recurrence. At an optimal GAGome score, the sensitivity was 90% (95% CI, 62%-100%) and the specificity was 51% (95% CI, 30%-71%). The positive predictive value (PPV) was 26% (95% CI, 4%-46%) and the negative predictive value (NPV) was 97% (95% CI, 87%-100%). The area under the curve (AUC) was 0.73 (95% CI, 0.72-0.74), and the sensitivity and specificity were consistent across subsets, with no significant interactions observed for sex, age, geographical area, or TNM stage.

At 12 months, a 10-point increase in the GAGome score was significantly associated with recurrence (HR, 1.62; 95% high-density interval (HDI), 1.11-2.30). Furthermore, among 134 evaluable patients after a median follow-up of 16 months (IQR, 12-18), 21 (16%) had experienced a radiologic recurrence during this period, with a median time interval between recurrence and urine collection of 0 days (IQR, –11 to 2). Additionally, among 19 patients who experienced true positive recurrence, the median lead time for GAGome recurrence was 4.2 months (IQR, 1.6-6.4) earlier.

“GAGome scores had very high sensitivity to detect ccRCC recurrence after surgery, leading to an NPV of 97%, but low specificity,” Saeed Dabestani, MD, associate professor in the Department of Translational Medicine, Division of Urological Cancers at Lund University in Sweden, wrote in the publication with study coinvestigators. “External validation foreseen in the study design, namely, cohort 2 of AURORAX-0087A, shall establish their usefulness to personalize follow-up imaging frequency, namely, reducing the number of radiological imaging and improving recurrence detection after surgery for ccRCC.”

Initially, patients on study were identified by presurgical CT, with the final study population selected postsurgically based on a pathological assessment of ccRCC with a Leibovich score (LS) of 5 or greater. Patients were also 18 years and older with at least 50% ccRCC histology if mixed subtypes. Those enrolled on the study provided urine samples at baseline before surgery and during post-surgical visits at 1, 3, 6, 9, 12, 15, and 18 months afterward or in conjunction with an off-schedule for GAGome measurements.

A total of 393 patients across 23 sites in Europe and North America were screened for eligibility between January 2020 and November 2021. After 162 patients met the inclusion criteria, a further 28 patients were excluded, 10 due to meeting any exclusion criteria, and 18 of whom were lost during follow-up. A total of 134 remained, which encompasses 34% of patients screened.

Patients on study had a median age of 64 years (IQR, 57-73), and 31% were female. A total of 87% of patients were based in Europe and the median 2003 LS score was 6 points (IQR, 5-8). Most patients had pathological TNM stage 3 disease (87%), Fuhrman/ISUP tumor grade 3 or 4 disease (94%), and a baseline GAGome score of 13 out of 100 (IQR, 7-23).

The primary end point of the study was the sensitivity and specificity of GAGome recurrence to radiological recurrence. Secondary end points included AUC, recurrence-free survival, and PPV and NPV values.

No severe adverse effects were reported related to study procedures. Notably, the study authors suggested that longer follow-up may help parse out patients identified as false positives with GAGome positivity, as high GAGome scores might be associated with the presence of minimal residual disease.

Reference

Dabestani S, Azawi NH, Campi R, et al. Urine glycosaminoglycan scores for surveillance of recurrence in intermediate- and high-risk nonmetastatic clear cell renal cell carcinoma—an observational prospective multicentre diagnostic test cohort study. Eur Urol Oncol. August 26, 2025. doi:10.1016/j.euo.2025.07.011